Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications

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Gupta, Sweta K.; Dinda, Amit K.; Potdar, Pravin D.; Mishra, Narayan C.

2013-01-01

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H and E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. - Highlights: • We successfully fabricated decellularized scaffold from cadaver goat-lung tissue. • Decellularized goat-lung scaffolds were found to be highly porous. • Skin derived MSC shows high cell viability and proliferation over the scaffold. • Phenotype of MSCs was well maintained over the scaffold. • The scaffold shows potential for applications in skin tissue engineering

Diagnosis of Peripheral Lung Lesions via Conventional Flexible Bronchoscopy with Multiplanar CT Planning

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Marianne Anastasia De Roza

2016-01-01

Full Text Available Background. Conventional flexible bronchoscopy has limited sensitivity in the diagnosis of peripheral lung lesions and is dependent on lesion size. However, advancement of CT imaging offers multiplanar reconstruction facilitating enhanced preprocedure planning. This study aims to report efficacy and safety while considering the impact of patient selection and multiplanar CT planning. Method. Prospective case series of patients with peripheral lung lesions suspected of having lung cancer who underwent flexible bronchoscopy (forceps biopsy and lavage. Endobronchial lesions were excluded. Patients with negative results underwent CT-guided transthoracic needle aspiration, surgical biopsy, or clinical-radiological surveillance to establish the final diagnosis. Results. 226 patients were analysed. The diagnostic yield of bronchoscopy was 80.1% (181/226 with a sensitivity of 84.2% and specificity of 100%. In patients with a positive CT-Bronchus sign, the diagnostic yield was 82.4% compared to 72.8% with negative CT-Bronchus sign (p=0.116. Diagnostic yield was 84.9% in lesions > 20 mm and 63.0% in lesions ≤ 20 mm (p=0.001. Six (2.7% patients had transient hypoxia and 2 (0.9% had pneumothorax. There were no serious adverse events. Conclusion. Flexible bronchoscopy with appropriate patient selection and preprocedure planning is more efficacious in obtaining a diagnosis in peripheral lung lesions compared to historical data. This trial is registered with ClinicalTrials.gov Identifier: NCT01374542.

Estimation of gas and tissue lung volumes by MRI: functional approach of lung imaging.

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Qanadli, S D; Orvoen-Frija, E; Lacombe, P; Di Paola, R; Bittoun, J; Frija, G

1999-01-01

The purpose of this work was to assess the accuracy of MRI for the determination of lung gas and tissue volumes. Fifteen healthy subjects underwent MRI of the thorax and pulmonary function tests [vital capacity (VC) and total lung capacity (TLC)] in the supine position. MR examinations were performed at inspiration and expiration. Lung volumes were measured by a previously validated technique on phantoms. Both individual and total lung volumes and capacities were calculated. MRI total vital capacity (VC(MRI)) was compared with spirometric vital capacity (VC(SP)). Capacities were correlated to lung volumes. Tissue volume (V(T)) was estimated as the difference between the total lung volume at full inspiration and the TLC. No significant difference was seen between VC(MRI) and VC(SP). Individual capacities were well correlated (r = 0.9) to static volume at full inspiration. The V(T) was estimated to be 836+/-393 ml. This preliminary study demonstrates that MRI can accurately estimate lung gas and tissue volumes. The proposed approach appears well suited for functional imaging of the lung.

Useful radiologic sign in diagnosis of peripheral lung cancer: Nucleohalo sign and its pathologic basis

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Wang, H.; Shi, D.

1994-01-01

The authors investigated the x-ray findings of 117 patients with peripheral lung cancer proved by operation and pathology, of them 35(29.9%) cases were found to have the 'nucleohalo sign', 6(13.6%) in 44 cases of solitary metastatic lung cancers, but none in 167 cases of benign lung nodular lesions and 4 cases of primary lung sarcoma and lymphoma. Radiologic and pathologic correlative study of the nucleohalo sign with surgical specimens of 14 lung cancers suggested that the cancerous parenchymas in nuclear areas were more than the interstitices in 12 cases and the other 2 were equal in both parenchymas and interstitices. Instead, the cancerous parenchymas in halo areas were less than cancerous interstitices in all cases. Dynamic observation of the 'nucleohalo sign' showed that this sign was an appearance of a stage in cancer growth. It is considered a very important sign in x-ray diagnosis of peripheral lung cancer, especially in the early diagnosis of lung cancer under or equal to 3 cm in diameter

A Comparative Study of Rat Lung Decellularization by Chemical Detergents for Lung Tissue Engineering

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Hamid Tebyanian

2017-12-01

CONCLUSION: Decellularized lung tissue can be used in the laboratory to study various aspects of pulmonary biology and physiology and also, these results can be used in the continued improvement of engineered lung tissue.

CT analysis of peripheral airway and lung lesions of patients with asthma and COPD

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Itoh, Takayuki; Tanaka, Hiroshi; Sahara, Shin; Ohnishi, Tetsuro; Abe, Shosaku; Ueno, Kan

2002-01-01

We compared peripheral airway and lung parenchyma images among patients with asthma, chronic obstructive pulmonary disease (COPD) and healthy controls using high-resolution CT images taken by a multidetector-row CT scanner (Aquillion, Toshiba, Japan). CT images were saved as digital image and communication (DICOM) files and %low attenuation area (LAA) (<-960 Hounsfield Unit) was calculated with the imaging software. %LAA was significantly increased in patients with COPD (p<0.0001) and smokers with stable asthma (p<0.01) as compared with healthy controls. In stable asthma, mucous plugging in the airway sometime appeared, while during asthma exacerbation small nodules and mosaic pattern of peripheral lung field appeared. Since smoker's patients with asthma have hyper-secretion of sputum due to smoking, mucous plugging and airway inflammation may easily occur and consequently air trapping may increase. In the future, image diagnosis of peripheral airway should develop for early detection of airway diseases as a non-invasive examination. On the other hand, micro focus X-ray computed tomography system (Hitachi Medico Technology Co., Japan) can display CT images closely similar to the pictures of microscopic findings and it will be a useful tool to analyze radiologic-pathologic correlations of peripheral airways and lung parenchyma. (author)

Fabrication and characterization of scaffold from cadaver goat-lung tissue for skin tissue engineering applications.

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Gupta, Sweta K; Dinda, Amit K; Potdar, Pravin D; Mishra, Narayan C

2013-10-01

The present study aims to fabricate scaffold from cadaver goat-lung tissue and evaluate it for skin tissue engineering applications. Decellularized goat-lung scaffold was fabricated by removing cells from cadaver goat-lung tissue enzymatically, to have cell-free 3D-architecture of natural extracellular matrix. DNA quantification assay and Hematoxylin and eosin staining confirmed the absence of cellular material in the decellularized lung-tissue. SEM analysis of decellularized scaffold shows the intrinsic porous structure of lung tissue with well-preserved pore-to-pore interconnectivity. FTIR analysis confirmed non-denaturation and well maintainance of collagenous protein structure of decellularized scaffold. MTT assay, SEM analysis and H&E staining of human skin-derived Mesenchymal Stem cell, seeded over the decellularized scaffold, confirms stem cell attachment, viability, biocompatibility and proliferation over the decellularized scaffold. Expression of Keratin18 gene, along with CD105, CD73 and CD44, by human skin-derived Mesenchymal Stem cells over decellularized scaffold signifies that the cells are viable, proliferating and migrating, and have maintained their critical cellular functions in the presence of scaffold. Thus, overall study proves the applicability of the goat-lung tissue derived decellularized scaffold for skin tissue engineering applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Protein signature of lung cancer tissues.

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Michael R Mehan

Full Text Available Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan to compare protein expression signatures of non small-cell lung cancer (NSCLC tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment.

Neural tissue engineering options for peripheral nerve regeneration.

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Gu, Xiaosong; Ding, Fei; Williams, David F

2014-08-01

Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Analysis of lung tissue particles among silicosis cases

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B Case

2005-10-01

Full Text Available Background and Aims:Lung tissue samples of several miners, millers, sandblaster, welders andconstruction workers with historical exposure to mineral particles were analyzed. These subjectshad significant respiratory exposure to silica particles and demanded compensation foroccupational lung diseases.Method: Lung tissue samples were observed under an Electron microscope with 10000Xmagnification. Mineral particles were sized and analyzed by EDS detector based on X-rayspectrophotometry.Results: The results have indicated that the lung particle burden of the subjects was closelyrelated to their occupational history. The highest level of mineral silica particles were found in thelungs of miners and sandblasters. The highest concentration of metallic particles was found in thelungs of welders and miners in ferric mining industry. Severity of lung fibrosis was directlyrelated to the lung free silica concentration. However, no association was found between particlediameter and severity of fibrosis. In addition, lung particle burden of silicotic cases with lungcancer contained a much higher concentration of metallic particles and asbestos fibres that thelung of those subject with silicosis only.Conclusion: Although workers in mining and construction may be predominantly exposed tosilica particles including quartz, the role of other mineral particles including asbestos fibres,metallic fibres and other minerals should be taken into account in the genesis of occupational lungdisease in particular lung cancer. Lung tissue sample analysis can provide valuable informationto assess the legal and compensation cases.

Bronchoscopic diagnosis of peripheral pulmonary lung cancer employing sedation with fentanyl and midazolam.

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Minami, Daisuke; Nakasuka, Takamasa; Ando, Chihiro; Iwamoto Md, Yoshitaka; Sato, Ken; Fujiwara, Keiichi; Shibayama, Takuo; Yonei Md PhD, Toshirou; Sato, Toshio

2017-09-01

Sedation with fentanyl and midazolam during bronchoscopic examination is commonly employed by pulmonary physicians in the USA and Europe. We assessed the efficacy of such sedation in the bronchoscopic diagnosis of peripheral lung cancer. We retrospectively evaluated data from 102 patients who underwent transbronchial biopsies (TBB) for diagnosis of peripheral lung cancer. Bronchoscopies with and without fentanyl were performed in 61 (group A) and 41 (group B) patients, respectively. Midazolam was administered to all patients. Medical records were retrieved, and between-group comparisons were made using unpaired Student's t-tests. The mean fentanyl dose was 49.5 μg (range: 10-100 μg), and midazolam doses in groups A and B were 4.29mg (range: 1-14mg) and 5.54mg (range: 1-12mg), respectively. Diagnostic histological specimens were obtained from 75.4% and 65.8% of group A and B patients, respectively (P = 0.30). The diagnostic sensitivities for lung cancer, via at least one of TBB, cytological brushing, or bronchial washing, in groups A and B were 88.5% and 70.4%, respectively (P = 0.035). Moreover, lesion diagnostic sensitivities, via at least one of TBB, cytological brushing, and bronchial washing, in groups A and B were 98.1% and 68.0%, respectively (P = 0.01). Fentanyl and midazolam sedation during bronchoscopy facilitated the diagnosis of peripheral pulmonary lung cancers. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection.

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DiPiazza, Anthony; Laniewski, Nathan; Rattan, Ajitanuj; Topham, David J; Miller, Jim; Sant, Andrea J

2018-07-01

Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza virus infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza virus infection in conjunction with intravascular labeling in vivo , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. These studies revealed that tissue-localized CD4 cells were globally distinct from vascular cells in expression of markers associated with transendothelial migration, residency, and micropositioning. Despite these differences, there was little evidence for remodeling of the viral epitope specificity or cytokine potential as cells transition from vasculature to the highly inflamed lung tissue. Our studies also distinguished cells in the pulmonary vasculature from peripheral circulating CD4 T cells, providing support for the concept that the pulmonary vasculature does not simply reflect circulating cells that are trapped within the narrow confines of capillary vessels but rather is enriched in transitional cells primed in the draining lymph node that have specialized potential to enter the lung tissue. IMPORTANCE CD4 T cells convey a multitude of functions in immunity to influenza, including those delivered in the lymph node and others conveyed by CD4 T cells that leave the lymph node, enter the blood, and extravasate into the lung tissue. Here, we show that the transition of recently primed CD4 cells detected in the lung vasculature undergo profound changes in expression of markers associated with tissue localization as

Peripheral blood count in preoperative radiotherapy (with radiomodificators) of lung cancer

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Demidchik, Yu.E.; Zharkov, V.V.; Prokhorova, V.I.; Rubanova, C.Z.

1989-01-01

Indices of peripheral blood in 215 patients with lung cancer during preoperative radiation using hyperglycemia or metronidazole are studied. It is shown that after preoperative radiotherapy, when radiomodifying effects are not used, the content of erythrocytes, thrombocytes, leukocytes, the concentration of hemoglobin in peripheral blood, as well as erythrocyte sedimentation rare didn't change. Functional disorders of the leukopoietic function and the thrombopoietic function of bone marrow when using metronidazole are registered when applying various types of preoperative radiotherapy. Lymphopenia is established when using various types of radiotherapy with radiomodificators

Trace element load in cancer and normal lung tissue

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Kubala-Kukus, A.; Braziewicz, J.; Banas, D.; Majewska, U.; Gozdz, S.; Urbaniak, A.

1999-01-01

Samples of malignant and benign human lung tissues were analysed by two complementary methods, i.e., particle induced X-ray emission (PIXE) and total reflection X-ray fluorescence (TRXRF). The concentration of trace elements of P, S, K, Ca, Ti, Cr, Mn, Fe, Cu, Zn, Se, Sr, Hg and Pb was determined in squamous cancer of lung tissue from 65 people and in the benign lung tumour tissue from 5 people. Several elements shows enhancement in cancerous lung tissue of women in comparison to men, i.e., titanium show maximum enhancement by 48% followed by Cr (20%) and Mn (36%). At the same time trace element concentration of Sr and Pb are declaimed by 30% and 20% in women population. Physical basis of used analytical methods, experimental set-up and the procedure of sample preparation are described

Circadian clocks are resounding in peripheral tissues.

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Andrey A Ptitsyn

2006-03-01

Full Text Available Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%-10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity.

Differential diagnosis of solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomograph

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Chu, Zhi-gang; Sheng, Bo; Liu, Meng-qi; Lv, Fa-jin; Li, Qi; Ouyang, Yu, E-mail: cyscitg@163.com [Hospital of Chongqing Medical University, Department of Radiology, Chongqing (China)

2016-10-15

Objectives: To clarify differences between solitary pulmonary inflammatory lesions and peripheral lung cancers with contrast-enhanced computed tomography. Methods: In total, 64 and 132 patients with solitary pulmonary inflammatory masses/nodules and peripheral lung cancers, respectively, were enrolled in this study. Their computed tomographic findings were summarized and compared retrospectively. Results: Compared with the peripheral lung cancers, the inflammatory lesions were located closer to the pleura (p<0.0001). The majority of the inflammatory lesions were patchy and oval-shaped (82.8%), whereas most of the tumors were lobulated (82.6%). Almost all the inflammatory cases were unclear (93.8%), whereas most of the tumors had speculated margins (72.7%). Computed tomography values were significantly higher for the inflammatory lesions than for the cancers (p<0.0001). More than half of the inflammatory lesions had defined necrosis (59.3%). Furthermore, 49.2% of the cancers enhanced inhomogeneously, but only 24.6% had ill-defined necrosis or cavities. The peripheral zones of 98.4% of the inflammatory lesions and 72.7% of the tumors were unclear, with peripheral scattered patches (92.2%) and beam-shaped opacity (66.7%) being the most common findings, respectively. Adjacent pleural thickening was more frequent for the inflammatory lesions than the cancers (95.3% vs. 21.1%, p<0.0001), whereas pleural indentation was found in 67.4% of the subjects with cancer. In addition, hilar (p=0.034) and mediastinal (p=0.003) lymphadenopathy were more commonly detected in the cancers than in the inflammatory cases. Conclusions: Contrast-enhanced computed tomography findings for pulmonary inflammatory lesions and peripheral lung cancers were significantly different in many aspects. Developing a comprehensive understanding of these differences is helpful for directing their management. (author)

The role of ultrasound-guided nephrostomy catheter drainage in the management of peripheral pyogenic lung abscess

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Amira A Gaballah

2018-01-01

Conclusion US-guided PTD using nephrostomy catheter for peripheral lung abscess is safe and effective; it can improve the outcome, shorten the duration and reduce the need for surgery in lung abscess treatment with less complications.

The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.

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Pragman, Alexa A; Lyu, Tianmeng; Baller, Joshua A; Gould, Trevor J; Kelly, Rosemary F; Reilly, Cavan S; Isaacson, Richard E; Wendt, Chris H

2018-01-09

Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection. Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R. Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue. This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that

Relative preservation of peripheral lung function in smoking-related pulmonary emphysema: assessment with {sup 99m}Tc-MAA perfusion and dynamic {sup 133}Xe SPET

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Suga, Kazuyoshi; Kume, Norihiko; Matsunaga, Naofumi; Ogasawara, Nobuhiko; Motoyama, Kazumi; Hara, Akiko; Matsumoto, Tsuneo [Department of Radiology, Yamaguchi University School of Medicine, Ube, Yamaguchi (Japan)

2000-07-01

In this study the cross-sectional functional differences between the central and peripheral lung in smokers with pulmonary emphysema were evaluated by lung perfusion and dynamic xenon-133 single-photon emission tomography (SPET). The subjects were 81 patients with a long-term smoking history and relatively advanced emphysema, 17 non-smoker patients with non-obstructive lung diseases and six healthy non-smokers. Regional lung functional difference between the peripheral and central lung was assessed in the upper, middle and lower lung zones by technetium-99m macroaggregated albumin SPET and dynamic {sup 133}Xe SPET. The distribution of emphysematous changes was assessed by density-mask computed tomography (CT) images which depicted abnormally low attenuation areas (LAAs) of less than -960 Hounsfield units. Two hundred and eighty-eight (59.2%) lung zones of 63 (77.7%) patients with pulmonary emphysema showed relative preservation of lung function in the peripheral lung, with a curvilinear band of normal perfusion (a stripe sign) and a significantly faster {sup 133}Xe half-clearance time (T{sub 1/2}) than in central lung (P<0.0001). Of these lung zones, 256 (88.8%) showed central-dominant LAA distributions on density-mask CT images, but the remaining 32 zones did not show any regional preference in LAA distribution. Conversely, 117 (24.0%) lung zones of 19 (23.4%) patients showed periphery-dominant perfusion defects and LAA distributions, with significantly prolonged T{sub 1/2} in the peripheral lung area (P<0.0001). The remaining 81 lung zones of the patients with pulmonary emphysema and all the lung zones of the healthy subjects and patients with non-obstructive lung diseases did not show a stripe sign, and no differences were observed in T{sub 1/2} values and LAA distributions between the central and peripheral lung. Relative preservation of peripheral lung function seems to be a characteristic feature in smoking-related pulmonary emphysema, and may indicate a

Histopathology of lung disease in the connective tissue diseases.

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Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

Telomerase in lung cancer diagnostics

International Nuclear Information System (INIS)

Kovkarova, E.; Stefanovski, T.; Dimov, A.; Naumovski, J.

2003-01-01

Background. Telomerase is a ribonucleoprotein that looks after the telomeric cap of the linear chromosomes maintaining its length. It is over expressed in tumour tissues, but not in normal somatic cells. Therefore the aim of this study was to determine the telomerase activity in lung cancer patients as novel marker for lung cancer detection evaluating the influence of tissue/cell obtaining technique. Material and methods. Using the TRAP (telomeric repeat amplification protocol), telomerase activity was determined in material obtained from bronchobiopsy (60 lung cancer patients compared with 20 controls) and washings from transthoracic fine needle aspiration biopsy performed in 10 patients with peripheral lung tumours. Results. Telomerase activity was detected in 75% of the lung cancer bronchobyopsies, and in 100% in transthoracic needle washings. Conclusions. Measurement of telomerase activity can contribute in fulfilling the diagnosis of lung masses and nodules suspected for lung cancer. (author)

Connective tissue diseases, multimorbidity and the ageing lung.

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Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

2016-05-01

Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

Pulmonary Abscess as a Complication of Transbronchial Lung Cryobiopsy.

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Skalski, Joseph H; Kern, Ryan M; Midthun, David E; Edell, Eric S; Maldonado, Fabien

2016-01-01

We present the case of a 49-year-old man who developed pulmonary abscess as a complication of transbronchial lung cryobiopsy. He had been receiving prednisone therapy, but otherwise had no specific risk factors for lung abscess. Cryobiopsy is a novel technique for obtaining peripheral lung parenchymal tissue for the evaluation of diffuse parenchymal lung diseases. Cryobiopsy is being increasingly proposed as an alternative to surgical lung biopsy or conventional bronchoscopic transbronchial forceps biopsy, but the safety profile of the procedure has not been fully appreciated. Pulmonary abscess has been rarely reported as a complication of other bronchoscopic procedures such as endobronchial ultrasound-guided needle biopsy, however, to our knowledge this is the first reported case of pulmonary abscess complicating peripheral lung cryobiopsy.

Comparison of contrast-to-noise ratios of transmission and dark-field signal in grating-based X-ray imaging for healthy murine lung tissue

International Nuclear Information System (INIS)

Schwab, Felix; Schleede, Simone; Hahn, Dieter

2013-01-01

Purpose: An experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. Materials and Methods: Lungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. Results: In all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p = 0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p = 0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p = 0.03). Conclusion: The contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI. (orig.)

Connective tissue-activating peptide III: a novel blood biomarker for early lung cancer detection.

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Yee, John; Sadar, Marianne D; Sin, Don D; Kuzyk, Michael; Xing, Li; Kondra, Jennifer; McWilliams, Annette; Man, S F Paul; Lam, Stephen

2009-06-10

There are no reliable blood biomarkers to detect early lung cancer. We used a novel strategy that allows discovery of differentially present proteins against a complex and variable background. Mass spectrometry analyses of paired pulmonary venous-radial arterial blood from 16 lung cancer patients were applied to identify plasma proteins potentially derived from the tumor microenvironment. Two differentially expressed proteins were confirmed in 64 paired venous-arterial blood samples using an immunoassay. Twenty-eight pre- and postsurgical resection peripheral blood samples and two independent, blinded sets of plasma from 149 participants in a lung cancer screening study (49 lung cancers and 100 controls) and 266 participants from the National Heart Lung and Blood Institute Lung Health Study (45 lung cancer and 221 matched controls) determined the accuracy of the two protein markers to detect subclinical lung cancer. Connective tissue-activating peptide III (CTAP III)/ neutrophil activating protein-2 (NAP-2) and haptoglobin were identified to be significantly higher in venous than in arterial blood. CTAP III/NAP-2 levels decreased after tumor resection (P = .01). In two independent population cohorts, CTAP III/NAP-2 was significantly associated with lung cancer and improved the accuracy of a lung cancer risk prediction model that included age, smoking, lung function (FEV(1)), and an interaction term between FEV(1) and CTAP III/NAP-2 (area under the curve, 0.84; 95% CI, 0.77 to 0.91) compared to CAPIII/NAP-2 alone. We identified CTAP III/NAP-2 as a novel biomarker to detect preclinical lung cancer. The study underscores the importance of applying blood biomarkers as part of a multimodal lung cancer risk prediction model instead of as stand-alone tests.

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 relationship between the peripheral lung cancer and the bronchi, pulmonary artery and vein: a multislice helical CT observation

International Nuclear Information System (INIS)

Liu Xueguo; Liang Mingzhu; Chen Cuifen; Qin Peixin; Zhong Guomei; He Yanguo; Liu Xiaobing; Han Mingqun; Yi Xianping; Wang Yong; Zhang Hao

2008-01-01

Objective: To investigate the relationships between the peripheral lung cancer and pulmonary vessels or bronchi by 16-row multislice computed tomography (MSCT) and analyze the related factors. Methods: Fifty-four patients with peripheral lung cancer confirmed pathologically underwent contrast-enhanced MSCT. Multiplanar reformation (MPR) and maximum intensity projection (MIP) in all patients were used to demonstrate the relationships between the peripheral lung cancer and pulmonary vessels, bronchi. The relationships were categorized five types: Type 1, erupted at the edge of nodule. Type 2, erupted at the center of nodule. Type 3, penetrated through the nodule. Type 4, contacting the nodule but stretched or encased. Type 5, contacting the nodule but smoothly compressed. The pathology type, stage, size, density and location of the peripheral lung cancer were recorded and the relationships with five types were evaluated by using Chi-square test and correlation analysis. Results: (1) Tumor-bronchi relationship: type 1 (33,61.1%) was more often seen in ≥2.0 cm and solid lesions with stage II-IV, while Type 2(14,25.9%) was often seen in < 2.0 cm and part-solid or non-solid lesions with stage I. (2) Tumor-PA relationship: Type 1 was more often seen in ≥2.0 cm and solid lesions with stage II-IV, while Type 2 was often seen in part-solid or non-solid lesions with stage I. (3) Tumor-PV relationship: type 4 was the most common type (29, 53.7%). Type 2 (13, 24.1%) was more often seen in part-solid or non-solid lesions. (4) Tumor-bronchi relationship and tumor-PA relationship had a positive correlation (r0.5265, P<0.01). Conclusions: MSCT can demonstrate the relations between the peripheral lung cancer and bronchi, PA and PV. It is useful for the differential diagnosis and prognosis evaluation of the lung cancer. (authors)

Imaging of tuberculosis. Pt. 5. Peripheral osteoarticular and soft-tissue tuberculosis

Energy Technology Data Exchange (ETDEWEB)

Hugosson, C. [Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Nyman, R.S. [Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Brismar, J. [Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Larsson, S.G. [Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Lindahl, S. [Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia); Lundstedt, C. [Dept. of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)

1996-07-01

Purpose: To assess frequency, location, and appearance of peripheral osteoarticular and soft-tissue tuberculosis (TB). Material and Methods: Twenty-five of 503 patients with TB had peripheral osteoarticular TB and 5 had soft-tissue TB. Chest radiography, CT, and MR imaging were applied. Results: The location of the osteoarticular lesion was articular/epiphyseal in 14 patients, articular/metaphyseal in 3, and metaphyseal without joint involvement in 3. Involvement of flat bone was found in 4 patients (5 lesions). The morphologic appearance was similar to that of a lytic tumour in 9 patients (10 lesions) and that of a destructive joint lesion in 16 patients. The soft-tissue TB in all 5 patients presented as an abscess. Twelve patients had a total of 20 additional sites of involvement: Chest in 9, abdomen in 4, spine in 4, the neck in 3, and the central nervous system in one patient. Conclusion: On the basis of radiologic appearance, it can be difficult to differentiate peripheral osteoarticular and soft-tissue TB from other degenerative, inflammatory, or neoplastic disorders, and the importance of a high awareness is stressed in order to reach an early diagnosis. (orig.).

Imaging of tuberculosis. Pt. 5. Peripheral osteoarticular and soft-tissue tuberculosis

International Nuclear Information System (INIS)

Hugosson, C.; Nyman, R.S.; Brismar, J.; Larsson, S.G.; Lindahl, S.; Lundstedt, C.

1996-01-01

Purpose: To assess frequency, location, and appearance of peripheral osteoarticular and soft-tissue tuberculosis (TB). Material and Methods: Twenty-five of 503 patients with TB had peripheral osteoarticular TB and 5 had soft-tissue TB. Chest radiography, CT, and MR imaging were applied. Results: The location of the osteoarticular lesion was articular/epiphyseal in 14 patients, articular/metaphyseal in 3, and metaphyseal without joint involvement in 3. Involvement of flat bone was found in 4 patients (5 lesions). The morphologic appearance was similar to that of a lytic tumour in 9 patients (10 lesions) and that of a destructive joint lesion in 16 patients. The soft-tissue TB in all 5 patients presented as an abscess. Twelve patients had a total of 20 additional sites of involvement: Chest in 9, abdomen in 4, spine in 4, the neck in 3, and the central nervous system in one patient. Conclusion: On the basis of radiologic appearance, it can be difficult to differentiate peripheral osteoarticular and soft-tissue TB from other degenerative, inflammatory, or neoplastic disorders, and the importance of a high awareness is stressed in order to reach an early diagnosis. (orig.)

Measurement of asbestos bodies in lung tissue of autopsy cases diagnosed with primary lung cancer

International Nuclear Information System (INIS)

Idei, Yuka; Kamada, Satoe; Matsumoto, Shoji; Ohnishi, Kazuo; Kitazawa, Riko; Kitazawa, Sohei

2007-01-01

To investigate the relation between asbestos-related lung cancer and the concentration of asbestos bodies in lung tissue, we analyzed the concentration in 24 autopsy cases diagnosed with primary lung cancer, with regard to the gender, age, histological type of lung cancer and occupation of each case. The asbestos bodies were measured according to Kohyama's method. Positive cases (more than 5,000 bodies per 1 g of dry lung tissue) were further analyzed for asbestosis and pleural plaques by chest X-ray and chest CT. Two cases exhibited more than 5,000 bodies, five cases between 1,000 and 5,000, and seventeen cases less than 1,000. The occupation of the two positive cases was not informative: one demonstrated neither asbestosis nor pleural plaques, and the other showed only pleural plaques. Although the number of cases of asbestos-related lung cancer is minimal among all lung cancer cases, the number of the former may exceed that of mesothelioma patients. Not only physicians but also radiologists, surgeons and pathologists need to collaborate in the diagnosis of asbestos-related lung cancer. (author)

'Multi-associations': predisposed to misinterpretation of peripheral tissue oxygenation and circulation in neonates.

Science.gov (United States)

Pichler, Gerhard; Pocivalnik, Mirjam; Riedl, Regina; Pichler-Stachl, Elisabeth; Morris, Nicholas; Zotter, Heinz; Müller, Wilhelm; Urlesberger, Berndt

2011-08-01

Interpretation of peripheral circulation in ill neonates is crucial but difficult. The aim was to analyse parameters potentially influencing peripheral oxygenation and circulation. In a prospective observational cohort study in 116 cardio-circulatory stable neonates, peripheral muscle near-infrared spectroscopy (NIRS) with venous occlusion was performed. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO(2)), fractional oxygen extraction (FOE), fractional tissue oxygen extraction (FTOE), haemoglobin flow (Hbflow), oxygen delivery (DO(2)), oxygen consumption (VO(2)), and vascular resistance (VR) were assessed. Correlation coefficients between NIRS parameters and demographic parameters (gestational age, birth weight, age, actual weight, diameter of calf, subcutaneous adipose tissue), monitoring parameters (heart rate, arterial oxygen saturation (SaO(2)), mean blood pressure (MAP), core/peripheral temperature, central/peripheral capillary refill time) and laboratory parameters (haemoglobin concentration (Hb-blood), pCO(2)) were calculated. All demographic parameters except for Hbflow and DO(2) correlated with NIRS parameters. Heart rate correlated with TOI, SvO(2), VO(2) and VR. SaO(2) correlated with FOE/FTOE. MAP correlated with Hbflow, DO(2), VO(2) and VR. Core temperature correlated with FTOE. Peripheral temperature correlated with all NIRS parameters except VO(2). Hb-blood correlated with FOE and VR. pCO(2) levels correlated with TOI and SvO(2). The presence of multiple interdependent factors associated with peripheral oxygenation and circulation highlights the difficulty in interpreting NIRS data. Nevertheless, these findings have to be taken into account when analysing peripheral oxygenation and circulation data.

Toward Transoral Peripheral Lung Access: Combining Continuum Robots and Steerable Needles.

Science.gov (United States)

Swaney, Philip J; Mahoney, Arthur W; Hartley, Bryan I; Remirez, Andria A; Lamers, Erik; Feins, Richard H; Alterovitz, Ron; Webster, Robert J

2017-03-01

Lung cancer is the most deadly form of cancer in part because of the challenges associated with accessing nodules for diagnosis and therapy. Transoral access is preferred to percutaneous access since it has a lower risk of lung collapse, yet many sites are currently unreachable transorally due to limitations with current bronchoscopic instruments. Toward this end, we present a new robotic system for image-guided trans-bronchoscopic lung access. The system uses a bronchoscope to navigate in the airway and bronchial tubes to a site near the desired target, a concentric tube robot to move through the bronchial wall and aim at the target, and a bevel-tip steerable needle with magnetic tracking to maneuver through lung tissue to the target under closed-loop control. In this work, we illustrate the workflow of our system and show accurate targeting in phantom experiments. Ex vivo porcine lung experiments show that our steerable needle can be tuned to achieve appreciable curvature in lung tissue. Lastly, we present targeting results with our system using two scenarios based on patient cases. In these experiments, phantoms were created from patient-specific computed tomography information and our system was used to target the locations of suspicious nodules, illustrating the ability of our system to reach sites that are traditionally inaccessible transorally.

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; 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

Toxicity After Central versus Peripheral Lung Stereotactic Body Radiation Therapy: A Propensity Score Matched-Pair Analysis

Energy Technology Data Exchange (ETDEWEB)

Mangona, Victor S. [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Aneese, Andrew M. [Oakland University William Beaumont School of Medicine, Rochester, Michigan (United States); Marina, Ovidiu; Hymas, Richard V. [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Ionascu, Dan; Robertson, John M. [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Oakland University William Beaumont School of Medicine, Rochester, Michigan (United States); Gallardo, Lori J. [Oakland University William Beaumont School of Medicine, Rochester, Michigan (United States); Department of Radiology, Beaumont Health System, Royal Oak, Michigan (United States); Grills, Inga Siiner, E-mail: igrills@beaumont.edu [Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan (United States); Oakland University William Beaumont School of Medicine, Rochester, Michigan (United States)

2015-01-01

Purpose: To compare toxicity after stereotactic body radiation therapy (SBRT) for “central” tumors—within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum—versus noncentral (“peripheral”) lung tumors. Methods and Materials: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non–small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/β=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ{sup 2} and 2-tailed t tests, adverse events with χ{sup 2} test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). Results: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral

[Fuzzing pattern recognition study on Raman spectrum of tumor peripheral tissue].

Science.gov (United States)

Luo, Lei; Zhao, Yuan-li; Ge, Xiang-hong; Zhang, Xiao-dong; Hao, Zhi-fang; Lü, Jing

2006-06-01

On the basis of some theories about fuzzing pattern recognition, the present article studied the data preprocessing of the Raman spectrum of tumor peripheral tissue, and feature extraction and selection. According to these features the authors improved the leaning towards the bigger membership function of trapezoidal distribution. The authors built the membership function of Raman spectrum of tumor peripheral tissue which belongs to malignant tumor on the basis of 40 specimens, and designed the classifier. The test of other 40 specimens showed that the discrimination of malignant tumor is 82.4%, while that of beginning tumor is 73.9%.

Emerging nanotechnology approaches in tissue engineering for peripheral nerve regeneration.

Science.gov (United States)

Cunha, Carla; Panseri, Silvia; Antonini, Stefania

2011-02-01

Effective nerve regeneration and functional recovery subsequent to peripheral nerve injury is still a clinical challenge. Autologous nerve graft transplantation is a feasible treatment in several clinical cases, but it is limited by donor site morbidity and insufficient donor tissue, impairing complete functional recovery. Tissue engineering has introduced innovative approaches to promote and guide peripheral nerve regeneration by using biomimetic conduits creating favorable microenvironments for nervous ingrowth, but despite the development of a plethora of nerve prostheses, few approaches have as yet entered the clinic. Promising strategies using nanotechnology have recently been proposed, such as the use of scaffolds with functionalized cell-binding domains, the use of guidance channels with cell-scale internally oriented fibers, and the possibility of sustained release of neurotrophic factors. This review addresses the fabrication, advantages, drawbacks, and results achieved by the most recent nanotechnology approaches in view of future solutions for peripheral nerve repair. Peripheral nerve repair strategies are very limited despite numerous advances on the field of neurosciences and regenerative medicine. This review discusses nanotechnology based strategies including scaffolds with functionalized cell binding domains, the use of guidance channels, and the potential use of sustained release neurotropic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

Science.gov (United States)

Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

2017-04-01

The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

Calculation of microplanar beam dose profiles in a tissue/lung/tissue phantom

International Nuclear Information System (INIS)

Company, F.Z.; Allen, B.J.

1998-01-01

Recent advances in synchrotron generated x-ray beams with a high fluence rate permit investigation of the application of an array of closely spaced, parallel or converging microplanar beams in radiotherapy. The proposed technique takes advantage of the hypothesized repair mechanism of capillary cells between alternate microbeam zones, which regenerates the lethally irradiated endothelial cells. The lateral and depth doses of 100 keV microplanar beams are investigated for different beam dimensions and spacings in a tissue, lung and tissue/lung/tissue phantom. The EGS4 Monte Carlo code is used to calculate dose profiles at different depths and bundles of beams (up to 20x20cm square cross section). The maximum dose on the beam axis (peak) and the minimum interbeam dose (valley) are compared at different depths, bundles, heights, widths and beam spacings. (author)

Characterizing the lung tissue mechanical properties using a micromechanical model of alveolar sac

Science.gov (United States)

Karami, Elham; Seify, Behzad; Moghadas, Hadi; Sabsalinejad, Masoomeh; Lee, Ting-Yim; Samani, Abbas

2017-03-01

According to statistics, lung disease is among the leading causes of death worldwide. As such, many research groups are developing powerful tools for understanding, diagnosis and treatment of various lung diseases. Recently, biomechanical modeling has emerged as an effective tool for better understanding of human physiology, disease diagnosis and computer assisted medical intervention. Mechanical properties of lung tissue are important requirements for methods developed for lung disease diagnosis and medical intervention. As such, the main objective of this study is to develop an effective tool for estimating the mechanical properties of normal and pathological lung parenchyma tissue based on its microstructure. For this purpose, a micromechanical model of the lung tissue was developed using finite element (FE) method, and the model was demonstrated to have application in estimating the mechanical properties of lung alveolar wall. The proposed model was developed by assembling truncated octahedron tissue units resembling the alveoli. A compression test was simulated using finite element method on the created geometry and the hyper-elastic parameters of the alveoli wall were calculated using reported alveolar wall stress-strain data and an inverse optimization framework. Preliminary results indicate that the proposed model can be potentially used to reconstruct microstructural images of lung tissue using macro-scale tissue response for normal and different pathological conditions. Such images can be used for effective diagnosis of lung diseases such as Chronic Obstructive Pulmonary Disease (COPD).

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....

Lung perfusion scintigraphy in the diagnosis of peripheral pulmonary stenosis in patients after repair of Fallot tetralogy

International Nuclear Information System (INIS)

Sabiniewicz, R.; Chojnicki, M.; Alszewicz-Baranowska, J.; Erecinski, J.; Romanowicz, G.; Lass, P.; Bandurski, T.

2002-01-01

The frequency of peripheral pulmonary artery stenosis in patients after surgical repair of tetralogy of Fallot (TOF) ranges from 20 to 40%. This can be either primary or secondary to the surgical intervention. The influence of resulting lung perfusion alterations on the life quality of patients is difficult to predict. The aim of this study was to compare the utility of the diagnostic procedures in this group of patients, with particular focus on lung perfusion scintigraphy. This study comprised 104 patients who underwent repair of TOF at ages from 5 months to 25 years. The patients have been followed up for from 4.2 to 25 years. On the basis of chest X-ray peripheral pulmonary artery stenosis was suspected in 11 patients, in 12 on the basis of echocardiography examination. Lung perfusion scintigraphy has been performed on 87 patients. The disturbances in lung perfusion (mostly in the left lung) were show by means of lung perfusion scintigraphy in 43 (49%) of patients. In 27 of them heart catheterisation has been performed. Angiography revealed stenosis of the lung artery branch in 15/43 (34.9%) patients with abnormal perfusion lung scan and in 4/44 (9%) in patients with normal perfusion lung scan. Intervention procedures were carried out on 10 patients. Lung perfusion scintigraphy may prove a valuable, non-invasive screening tool in the assessment of patients after TOF repair, although both false-negative and false positive results may happen. Therefore, it should play an auxiliary role together with other diagnostic modalities. (author)

Pecularities of peripheral blood morphological content in rats in case of combined irradiation of lungs and thyroid

International Nuclear Information System (INIS)

Kulikova, S.B.; Korzhavin, A.N.

1988-01-01

Indices of morphological content of peripheral blood were studied in male rats at 1, 3, 7, 14 days following intratracheal administration of oxide suspension of 147 Nd + 147 Pm and oral administration of 131 I. By 14 days the doses for lungs and thyroid were 5 Gy and 10 Gy respectively. It was shown that the doses of 134 I don't influence morphological indices of peripheral blood but combined effect of radioisotopes leads to moderate increase of leukocyte, lymphocytes and neutrophils. Manifestation of changes in white blood turned out to be less than in case of similar effect of stable isotope on the lungs. Minor shifts in white blood and severity of patholoanatomical picture of inflammatory process in the lungs in case of radioactive isotopes effect can be attributed to specific effect of ionizing radiation. 4 refs.; 2 tabs

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

Sexual dimorphism in hepatic, adipose tissue and peripheral tissue insulin sensitivity in obese humans

Directory of Open Access Journals (Sweden)

Kasper W. ter Horst

2015-11-01

Full Text Available Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue and whole-body insulin sensitivity between severely obese men and women. In this study, we aimed to determine the differences in glucose metabolism between severely obese men and women using tissue-specific measurements of insulin sensitivity. Insulin sensitivity was compared between age and body mass index (BMI-matched obese men and women by a two-step euglycemic hyperinsulinemic clamp with infusion of [6,6-2H2]glucose. Basal endogenous glucose production and insulin sensitivity of the liver, adipose tissue and peripheral tissues were assessed. Liver fat content was assessed by proton magnetic resonance spectroscopy in a subset of included subjects. We included 46 obese men and women (age, 48±2 vs 46±2 years, p=0.591; BMI, 41±1 vs 41±1 kg/m2, p=0.832. There was no difference in basal endogenous glucose production (14.4±1.0 vs 15.3±0.5 µmol•kg fat-free mass-1•min-1, p=0.410, adipose tissue insulin sensitivity (insulin-mediated suppression of free fatty acids, 71.6±3.6 vs 76.1±2.6%, p=0.314 or peripheral insulin sensitivity (insulin-stimulated rate of disappearance of glucose, 26.2±2.1 vs 22.7±1.7 µmol•kg-1•min-1, p=0.211. Obese men were characterized by lower hepatic insulin sensitivity (insulin-mediated suppression of endogenous glucose production, 61.7±4.1 vs 72.8±2.5% in men vs women, resp., p=0.028. Finally, these observations could not be explained by differences in liver fat content (men vs women, 16.5±3.1 vs 16.0±2.5%, p=0.913, n=27.We conclude that obese men have lower hepatic, but comparable adipose tissue and peripheral tissue, insulin sensitivity compared to similarly obese women. Hepatic insulin resistance may

Diagnostic utility of LunX mRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer

Directory of Open Access Journals (Sweden)

Tian Zhigang

2008-05-01

Full Text Available Abstract Background Progress in lung cancer is hampered by the lack of clinically useful diagnostic markers. The goal of this study was to provide a detailed evaluation of lung cancer tumor markers indicative of molecular abnormalities and to assess their diagnostic utility in non-small cell lung cancer (NSCLC patients. Methods Quantitative real-time RT-PCR was used to determine LunX, CK19, CEA, VEGF-C and hnRNP A2/B1 mRNA levels in peripheral blood and pleural fluid from NSCLC patients, compared with those from patients with other epithelial cancer (esophagus cancer and breast cancer, benign lung disease (pneumonia and tuberculo pleurisy and from healthy volunteers. Results In peripheral blood LunX mRNA was detectable in 75.0% (33/44 of patients with NSCLC, but not in patients with other epithelial cancer (0/28, benign lung disease (0/10 or in healthy volunteers (0/15. In contrast, all other genetic markers were detected in patients with either NSCLC, other epithelia cancer or benign lung disease, and in healthy volunteers. The expression level and positive rate of LunX mRNA in peripheral blood correlated with the pathologic stage of NSCLC (P LunX mRNA was detected in 92.9% (13/14 of malignant pleural fluid samples and was the only marker whose expression level was significantly different between malignant and benign pleural fluid (P LunX mRNA in the peripheral blood of NSCLC patients decreased shortly after clinical treatment (P = 0.005. Conclusion Of several commonly used genetic markers, LunX mRNA is the most specific gene marker for lung cancer and has potential diagnostic utility when measured in the peripheral blood and pleural fluid of NSCLC patients.

Current lung water measurement methods in man

International Nuclear Information System (INIS)

Basset, G.; Moreau, F.; Marsac, J.; Capitini, R.; Botter, F.

1979-01-01

Two kinds of tracer method are used to estimate the lung water pools differing by the tracer intake and the sector observed. Airborne intake gives an estimate of the tissues irrigated by the lung and bronchial circulation, whereas vascular intake only shows the sectors perfused by the lung flow. Either of these methods is suitable for a general or regional analysis. In general methods the tracer is followed at the lung exit on expired air for the first method, on peripheral arterial blood for the second. Regional methods imply partial or whole-lung external detection systems [fr

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Single Peripheral Lung Metastases

Energy Technology Data Exchange (ETDEWEB)

Snider, James W.; Oermann, Eric K.; Chen, Viola; Rabin, Jennifer; Suy, Simeng; Yu, Xia [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Vahdat, Saloomeh [Department of Pathology, Georgetown University Hospital, Washington, DC (United States); Collins, Sean P. [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Banovac, Filip [Department of Radiology, Georgetown University Hospital, Washington, DC (United States); Anderson, Eric [Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Hospital, Washington, DC (United States); Collins, Brian T., E-mail: collinsb@gunet.georgetown.edu [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States)

2012-06-29

Standard treatment for operable patients with single peripheral lung metastases is metastasectomy. We report mature CyberKnife outcomes for high-risk surgical patients with biopsy proven single peripheral lung metastases. Twenty-four patients (median age 73 years) with a mean maximum tumor diameter of 2.5 cm (range, 0.8–4.5 cm) were treated over a 6-year period extending from September 2004 to September 2010 and followed for a minimum of 1 year or until death. A mean dose of 52 Gy (range, 45–60 Gy) was delivered to the prescription isodose line in three fractions over a 3–11 day period (mean, 7 days). At a median follow-up of 20 months, the 2-year Kaplan–Meier local control and overall survival rates were 87 and 50%, respectively. CyberKnife with fiducial tracking is an effective treatment for high-risk surgical patients with single small peripheral lung metastases. Trials comparing CyberKnife with metastasectomy for operable patients are necessary to confirm equivalence.

Electromagnetic navigation diagnostic bronchoscopy for small peripheral lung lesions.

Science.gov (United States)

Makris, D; Scherpereel, A; Leroy, S; Bouchindhomme, B; Faivre, J-B; Remy, J; Ramon, P; Marquette, C-H

2007-06-01

The present study prospectively evaluated the diagnostic yield and safety of electromagnetic navigation-guided bronchoscopy biopsy, for small peripheral lung lesions in patients where standard techniques were nondiagnostic. The study was conducted in a tertiary medical centre on 40 consecutive patients considered unsuitable for straightforward surgery or computed tomography (CT)-guided transthoracic needle aspiration biopsy, due to comorbidities. The lung lesion diameter was mean+/-sem 23.5+/-1.5 mm and the depth from the visceral-costal pleura was 14.9+/-2 mm. Navigation was facilitated by an electromagnetic tracking system which could detect a position sensor incorporated into a flexible catheter advanced through a bronchoscope. Information obtained during bronchoscopy was superimposed on previously acquired CT data. Divergence between CT data and data obtained during bronchoscopy was calculated by the system's software as a measure of navigational accuracy. All but one of the target lesions was reached and the overall diagnostic yield was 62.5% (25-40). Diagnostic yield was significantly affected by CT-to-body divergence; yield was 77.2% when estimated divergence was drainage was required in one case. Electromagnetic navigation-guided bronchoscopy has the potential to improve the diagnostic yield of transbronchial biopsies without additional fluoroscopic guidance, and may be useful in the early diagnosis of lung cancer, particularly in nonoperable patients.

Utilization of 14C-tyrosine in brain and peripheral tissues of developmentally protein malnourished rats

International Nuclear Information System (INIS)

Miller, M.; Leahy, J.P.; McConville, F.; Morgane, P.J.; Resnick, O.

1978-01-01

Prior studies of developmentally protein malnourished rats have reported substantial changes in brain and peripheral utilization of 14 C-leucine, 14 C-phenylalanine, and 14 C-tryptophan. In the present study rats born to dams fed a low protein diet (8% casein) compared to the offspring of control rats fed a normal diet (25% casein) showed few significant differences in the uptake and incorporation of 14 C-tyrosine into brain and peripheral tissues from birth to age 21 days. At birth, the 8% casein pups exhibited significant decreases in brain and peripheral tissue incorporation of tracer only at short post-injection times (10 and 20 min), but not at longer intervals (90 and 180 min). During ontogenetic development (Days 5-21), the 8% casein rats showed significant increases in uptake of 14 C-tyrosine into the brain and peripheral tissues on Day 11 and a significantly higher percent incorporation of tracer into brain protein on Day 21 as compared to the 25% casein rats. For the most part, there were no significant changes in incorporation of radioactivity in peripheral tissues for the 2 diet groups on these post-birth days. Overall, the data indicates that developmental protein malnutrition causes relatively fewer changes in brain and peripheral utilization of the semi-essential amino acid tyrosine than those observed in previous studies with essential amino acids

Analysis of lung tissue using ion beams

International Nuclear Information System (INIS)

Alvarez, J.L.; Barrera, R.; Miranda, J.

2002-01-01

In this work a comparative study is presented of the contents of metals in lung tissue from healthy patients and with lung cancer, by means of two analytical techniques: Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS). The samples of cancerous tissue were taken from 26 autopsies made to individuals died in the National Institute of Respiratory Disease (INER), 22 of cancer and 4 of other non-cancer biopsies. When analyzing the entirety of the samples, in the cancerous tissues, there were increments in the concentrations of S (4%), K (635%), Co (85%) and Cu (13%). Likewise, there were deficiencies in the concentrations of Cl (59%), Ca (6%), Fe (26%) and Zn (7%). Only in the cancerous tissues there were appearances of P, Ca, Ti, V, Cr, Mn, Ni, Br and Sr. The tissue samples were classified according to cancer types (adenocarcinomas, epidermoides and of small cell carcinoma), personal habits (smokers and alcoholic), genetic predisposition and residence place. There was a remarkable decrease in the concentration of Ca and a marked increment in the Cu in the epidermoide tissue samples with regard to those of adenocarcinoma or of small cells cancer. Also, decrements were detected in K and increments of Fe, Co and Cu in the sample belonging to people that resided in Mexico City with regard to those that resided in the State of Mexico

Different histological subtypes of peripheral lung cancer based on emphysema distribution in patients with both airflow limitation and CT-determined emphysema.

Science.gov (United States)

Shin, Beomsu; Shin, Sumin; Chung, Myung Jin; Lee, Hyun; Koh, Won-Jung; Kim, Hojoong; Park, Hye Yun

2017-02-01

The histological subtypes by peripheral tumor location remain uncharacterized in COPD patients with emphysema. We investigated histologic subtypes of peripheral lung cancers based on the context of heterogeneous emphysema distribution in patients with airflow limitation and CT-determined emphysema. A retrospective, cross-sectional study was conducted using data from 754 patients with airflow limitation and newly-diagnosed primary lung cancers from February 2013 to February 2015. Of these, 230 patients had emphysema, as determined by computed tomography software designed to quantify emphysema. Among the 230 patients, the most common subtype in central lesions (n=84) was squamous cell carcinoma (SCC) (n=64/84, 76%). Adenocarcinoma (ADC) was more frequently observed in peripheral lesions (n=146) than central lesions (58/146 [40%] vs. 4/84 [5%], pemphysema than emphysema areas (43/74 [58%] vs. 15/72 [21%], pemphysema areas than areas without emphysema (44/72 [61%] vs. 13/74 [18%], pemphysema, the main histological subtype of peripheral lung cancer was SCC in emphysema areas and ADC in areas without emphysema. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

Science.gov (United States)

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; pmotor dysfunction (90% vs. 35%; pesophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

'Multi-associations': predisposed to misinterpretation of peripheral tissue oxygenation and circulation in neonates

International Nuclear Information System (INIS)

Pichler, Gerhard; Pocivalnik, Mirjam; Pichler-Stachl, Elisabeth; Morris, Nicholas; Zotter, Heinz; Müller, Wilhelm; Urlesberger, Berndt; Riedl, Regina

2011-01-01

Interpretation of peripheral circulation in ill neonates is crucial but difficult. The aim was to analyse parameters potentially influencing peripheral oxygenation and circulation. In a prospective observational cohort study in 116 cardio-circulatory stable neonates, peripheral muscle near-infrared spectroscopy (NIRS) with venous occlusion was performed. Tissue oxygenation index (TOI), mixed venous oxygenation (SvO 2 ), fractional oxygen extraction (FOE), fractional tissue oxygen extraction (FTOE), haemoglobin flow (Hbflow), oxygen delivery (DO 2 ), oxygen consumption (VO 2 ), and vascular resistance (VR) were assessed. Correlation coefficients between NIRS parameters and demographic parameters (gestational age, birth weight, age, actual weight, diameter of calf, subcutaneous adipose tissue), monitoring parameters (heart rate, arterial oxygen saturation (SaO 2 ), mean blood pressure (MAP), core/peripheral temperature, central/peripheral capillary refill time) and laboratory parameters (haemoglobin concentration (Hb-blood), pCO 2 ) were calculated. All demographic parameters except for Hbflow and DO 2 correlated with NIRS parameters. Heart rate correlated with TOI, SvO 2 , VO 2 and VR. SaO 2 correlated with FOE/FTOE. MAP correlated with Hbflow, DO 2 , VO 2 and VR. Core temperature correlated with FTOE. Peripheral temperature correlated with all NIRS parameters except VO 2 . Hb-blood correlated with FOE and VR. pCO 2 levels correlated with TOI and SvO 2 . The presence of multiple interdependent factors associated with peripheral oxygenation and circulation highlights the difficulty in interpreting NIRS data. Nevertheless, these findings have to be taken into account when analysing peripheral oxygenation and circulation data

Nerve autografts and tissue-engineered materials for the repair of peripheral nerve injuries: a 5-year bibliometric analysis

Directory of Open Access Journals (Sweden)

Yuan Gao

2015-01-01

Full Text Available With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and large-gap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "pe-ripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany, Washington University (USA, and Nantong University (China. The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad-ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.

Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors

International Nuclear Information System (INIS)

Ohashi, Toshio; Takeda, Atsuya; Shigematsu, Naoyuki; Kunieda, Etsuo; Ishizaka, Akitoshi; Fukada, Junichi; Deloar, Hossain M.; Kawaguchi, Osamu; Takeda, Toshiaki; Takemasa, Kazuhiko; Isobe, Kouichi; Kubo, Atsushi

2005-01-01

Purpose: To evaluate long-term pulmonary toxicity of stereotactic radiotherapy (SRT) by pulmonary function tests (PFTs) performed before and after SRT for small peripheral lung tumors. Methods and Materials: A total of 17 lesions in 15 patients with small peripheral lung tumors, who underwent SRT between February 2000 and April 2003, were included in this study. Twelve patients had primary lung cancer, and 3 patients had metastatic lung cancer. Primary lung cancer was T1-2N0M0 in all cases. Smoking history was assessed by the Brinkman index (number of cigarettes smoked per day multiplied by number of years of smoking). Prescribed radiation doses at the 80% isodose line were 40-60 Gy in 5-8 fractions. PFTs were performed immediately before SRT and 1 year after SRT. Test parameters included total lung capacity (TLC), vital capacity (VC), forced expiratory volume in 1 s (FEV1.0), and diffusing capacity of lung for carbon monoxide (DLCO). PFT changes were evaluated in relation to patient- and treatment-related factors, including age, the Brinkman index, internal target volume, the percentages of lung volume irradiated with >15, 20, 25, and 30 Gy (V15, V20, V25, and V30, respectively), and mean lung dose. Results: There were no significant changes in TLC, VC, or FEV1.0 before vs. after SRT. The mean percent change from baseline in DLCO was significantly increased by 128.2%. Univariate and multivariate analyses revealed a correlation between DLCO and the Brinkman index. Conclusions: One year after SRT as compared with before SRT, there were no declines in TLC, VC, and FEV1.0. DLCO improved in patients who had been heavy smokers before SRT, suggesting a correlation between DLCO and smoking cessation. SRT seems to be tolerable in view of long-term lung function

Up-regulation of ALG-2 in hepatomas and lung cancer tissue

DEFF Research Database (Denmark)

la Cour, Jonas Marstrand; Mollerup, Jens; Winding, Pernille

2003-01-01

, a result confirmed by immunohistochemical analysis. Staining of four different lung cancer tissue microarrays including specimens of 263 patients showed that ALG-2 is mainly localized to epithelial cells and significantly up-regulated in small-cell lung cancers and in non-small-cell lung cancers. Our...... using Western blot analysis and immunohistochemistry. Western blot analysis of 15 different adult mouse tissues demonstrated that ALG-2 is ubiquitously expressed. We found that ALG-2 was more than threefold overexpressed in rat liver hepatoma compared to normal rat liver using Western blot analysis...

Thermal Ablation of Lung Tissue: In Vivo Experimental Comparison of Microwave and Radiofrequency

International Nuclear Information System (INIS)

Crocetti, Laura; Bozzi, Elena; Faviana, Pinuccia; Cioni, Dania; Della Pina, Clotilde; Sbrana, Alberto; Fontanini, Gabriella; Lencioni, Riccardo

2010-01-01

This study was designed to compare feasibility, safety, and effectiveness of microwave (MW) ablation versus radiofrequency (RF) ablation of lung tissue in a rabbit model. Twenty New Zealand White rabbits were submitted to MW (n = 10, group A) or RF ablation (n = 10, group B). The procedures were performed with a prototype MW ablation device with a 1.6-cm radiating section antenna (Valleylab MW Ablation System) and with a 2-cm exposed-tip RF electrode (Cool-tip RF Ablation System). At immediate computed tomography increase in density, maximum diameters (D1-D3) of ablation zones were measured and ablation volume was calculated. Histopathologic assessment was performed 3 and 7 days after the procedure. Technical success was achieved in nine of 10 rabbits in each group. One death occurred in group B. Complications included pneumothorax (group A, n = 4; group B, n = 4), abscess (group A, n = 1; group B, n = 1), and thoracic wall burn (group A, n = 4). No significant differences were demonstrated in attenuation increase (P = 0.73), dimensions (P = 0.28, 0.86, 0.06, respectively, comparing D1-D3) and volume (P = 0.17). At histopathology, ablation zones were similar, with septal necrosis, edema, hemorrhage, and peripheral lymphocytic infiltrate. Complete thrombosis of more than 90% of vessels up to 2 mm in diameter was depicted at the periphery of the ablation zone in group A specimens. In group B specimens, complete thrombosis was depicted in 20% of vessels. Feasibility and safety of MW and RF ablation are similar in a lung rabbit model. MW ablation produces a greater damage to peripheral small vessels inducing thrombosis.

Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

International Nuclear Information System (INIS)

Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

2013-01-01

Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

Pharmacokinetics of 2-nitroimidazole hypoxic cell radiosensitizers in rodent peripheral nervous tissue

International Nuclear Information System (INIS)

Sasai, K.; Shibamoto, Y.; Abe, M.; Takahashi, M.; Ito, T.; Nishimoto, S.

1990-01-01

The concentrations of seven 2-nitroimidazoles - including misonidazole, etanidazole (SR-2508), pimonidazole (Ro 03-8799), desmethylmisonidazole (Ro 05-9963), RK28, RP170 and KU2285 - were measured in the sciatic nerves of C3H/He mice using reverse-phase high-performance liquid chromatography. The apparent biological half-lives of the compounds in the peripheral nerves were correlated to their hydrophilicity: the more hydrophilic the compound, the longer the apparent biological half-life in the peripheral nervous tissue of the mice. Measurement of drug exposure in the rodent peripheral nervous system, rather than in the brain, was a better indicator for estimating the occurrence of clinical peripheral neuropathy by 2-nitroimidazoles. (author)

Pharmacokinetics of 2-nitroimidazole hypoxic cell radiosensitizers in rodent peripheral nervous tissue

Energy Technology Data Exchange (ETDEWEB)

Sasai, K.; Shibamoto, Y.; Abe, M. (Kyoto Univ. (Japan). Faculty of Medicine); Takahashi, M. (Kyoto Univ. (Japan). Chest Disease Research Inst.); Ito, T.; Nishimoto, S. (Kyoto Univ. (Japan). Faculty of Engineering)

1990-05-01

The concentrations of seven 2-nitroimidazoles - including misonidazole, etanidazole (SR-2508), pimonidazole (Ro 03-8799), desmethylmisonidazole (Ro 05-9963), RK28, RP170 and KU2285 - were measured in the sciatic nerves of C3H/He mice using reverse-phase high-performance liquid chromatography. The apparent biological half-lives of the compounds in the peripheral nerves were correlated to their hydrophilicity: the more hydrophilic the compound, the longer the apparent biological half-life in the peripheral nervous tissue of the mice. Measurement of drug exposure in the rodent peripheral nervous system, rather than in the brain, was a better indicator for estimating the occurrence of clinical peripheral neuropathy by 2-nitroimidazoles. (author).

Peripheral tissue homing receptor control of naïve, effector, and memory CD8 T cell localization in lymphoid and non-lymphoid tissues.

Science.gov (United States)

Brinkman, C Colin; Peske, J David; Engelhard, Victor Henry

2013-01-01

T cell activation induces homing receptors that bind ligands on peripheral tissue vasculature, programing movement to sites of infection and injury. There are three major types of CD8 effector T cells based on homing receptor expression, which arise in distinct lymphoid organs. Recent publications indicate that naïve, effector, and memory T cell migration is more complex than once thought; while many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and contain central memory precursors. LN re-entry can depend on CD62L or peripheral tissue homing receptors. Memory T cells in LN tend to express the same homing receptors as their forebears, but often are CD62Lneg. Homing receptors also control CD8 T cell tumor entry. Tumor vasculature has low levels of many peripheral tissue homing receptor ligands, but portions of it resemble high endothelial venules (HEV), enabling naïve T cell entry, activation, and subsequent effector activity. This vasculature is associated with positive prognoses in humans, suggesting it may sustain ongoing anti-tumor responses. These findings reveal new roles for homing receptors expressed by naïve, effector, and memory CD8 T cells in controlling entry into lymphoid and non-lymphoid tissues.

No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

Energy Technology Data Exchange (ETDEWEB)

Stanic, Sinisa, E-mail: sinisa.stanic@carle.com [Carle Cancer Center and University of Illinois College of Medicine, Urbana, Illinois (United States); Paulus, Rebecca [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Timmerman, Robert D. [University of Texas Southwestern, Dallas, Texas (United States); Michalski, Jeff M. [Washington University, St. Louis, Missouri (United States); Barriger, Robert B. [Indiana University, Indianapolis, Indiana (United States); Bezjak, Andrea [Princess Margaret Cancer Center, Toronto, Ontario (Canada); Videtic, Gregory M.M. [Cleveland Clinic Foundation, Cleveland, Ohio (United States); Bradley, Jeffrey [Washington University, St. Louis, Missouri (United States)

2014-04-01

Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT.

No Clinically Significant Changes in Pulmonary Function Following Stereotactic Body Radiation Therapy for Early- Stage Peripheral Non-Small Cell Lung Cancer: An Analysis of RTOG 0236

International Nuclear Information System (INIS)

Stanic, Sinisa; Paulus, Rebecca; Timmerman, Robert D.; Michalski, Jeff M.; Barriger, Robert B.; Bezjak, Andrea; Videtic, Gregory M.M.; Bradley, Jeffrey

2014-01-01

Purpose: To investigate pulmonary function test (PFT) results and arterial blood gas changes (complete PFT) following stereotactic body radiation therapy (SBRT) and to see whether baseline PFT correlates with lung toxicity and overall survival in medically inoperable patients receiving SBRT for early stage, peripheral, non-small cell lung cancer (NSCLC). Methods and Materials: During the 2-year follow-up, PFT data were collected for patients with T1-T2N0M0 peripheral NSCLC who received effectively 18 Gy × 3 in a phase 2 North American multicenter study (Radiation Therapy Oncology Group [RTOG] protocol 0236). Pulmonary toxicity was graded by using the RTOG SBRT pulmonary toxicity scale. Paired Wilcoxon signed rank test, logistic regression model, and Kaplan-Meier method were used for statistical analysis. Results: At 2 years, mean percentage predicted forced expiratory volume in the first second and diffusing capacity for carbon monoxide declines were 5.8% and 6.3%, respectively, with minimal changes in arterial blood gases and no significant decline in oxygen saturation. Baseline PFT was not predictive of any pulmonary toxicity following SBRT. Whole-lung V5 (the percentage of normal lung tissue receiving 5 Gy), V10, V20, and mean dose to the whole lung were almost identical between patients who developed pneumonitis and patients who were pneumonitis-free. Poor baseline PFT did not predict decreased overall survival. Patients with poor baseline PFT as the reason for medical inoperability had higher median and overall survival rates than patients with normal baseline PFT values but with cardiac morbidity. Conclusions: Poor baseline PFT did not appear to predict pulmonary toxicity or decreased overall survival after SBRT in this medically inoperable population. Poor baseline PFT alone should not be used to exclude patients with early stage lung cancer from treatment with SBRT

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

Science.gov (United States)

Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.; Vashakidze, Sergo

2017-01-01

ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

Science.gov (United States)

Kempker, Russell R; Heinrichs, M Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A; Blumberg, Henry M; Vashakidze, Sergo

2017-06-01

Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

Automating the expert consensus paradigm for robust lung tissue classification

Science.gov (United States)

Rajagopalan, Srinivasan; Karwoski, Ronald A.; Raghunath, Sushravya; Bartholmai, Brian J.; Robb, Richard A.

2012-03-01

Clinicians confirm the efficacy of dynamic multidisciplinary interactions in diagnosing Lung disease/wellness from CT scans. However, routine clinical practice cannot readily accomodate such interactions. Current schemes for automating lung tissue classification are based on a single elusive disease differentiating metric; this undermines their reliability in routine diagnosis. We propose a computational workflow that uses a collection (#: 15) of probability density functions (pdf)-based similarity metrics to automatically cluster pattern-specific (#patterns: 5) volumes of interest (#VOI: 976) extracted from the lung CT scans of 14 patients. The resultant clusters are refined for intra-partition compactness and subsequently aggregated into a super cluster using a cluster ensemble technique. The super clusters were validated against the consensus agreement of four clinical experts. The aggregations correlated strongly with expert consensus. By effectively mimicking the expertise of physicians, the proposed workflow could make automation of lung tissue classification a clinical reality.

Data-driven classification of ventilated lung tissues using electrical impedance tomography

International Nuclear Information System (INIS)

Gómez-Laberge, Camille; Hogan, Matthew J; Elke, Gunnar; Weiler, Norbert; Frerichs, Inéz; Adler, Andy

2011-01-01

Current methods for identifying ventilated lung regions utilizing electrical impedance tomography images rely on dividing the image into arbitrary regions of interest (ROI), manually delineating ROI, or forming ROI with pixels whose signal properties surpass an arbitrary threshold. In this paper, we propose a novel application of a data-driven classification method to identify ventilated lung ROI based on forming k clusters from pixels with correlated signals. A standard first-order model for lung mechanics is then applied to determine which ROI correspond to ventilated lung tissue. We applied the method in an experimental study of 16 mechanically ventilated swine in the supine position, which underwent changes in positive end-expiratory pressure (PEEP) and fraction of inspired oxygen (F I O 2 ). In each stage of the experimental protocol, the method performed best with k = 4 and consistently identified 3 lung tissue ROI and 1 boundary tissue ROI in 15 of the 16 subjects. When testing for changes from baseline in lung position, tidal volume, and respiratory system compliance, we found that PEEP displaced the ventilated lung region dorsally by 2 cm, decreased tidal volume by 1.3%, and increased the respiratory system compliance time constant by 0.3 s. F I O 2 decreased tidal volume by 0.7%. All effects were tested at p < 0.05 with n = 16. These findings suggest that the proposed ROI detection method is robust and sensitive to ventilation dynamics in the experimental setting

Tracking Regional Tissue Volume and Function Change in Lung Using Image Registration

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Kunlin Cao

2012-01-01

Full Text Available We have previously demonstrated the 24-hour redistribution and reabsorption of bronchoalveolar lavage (BAL fluid delivered to the lung during a bronchoscopic procedure in normal volunteers. In this work we utilize image-matching procedures to correlate fluid redistribution and reabsorption to changes in regional lung function. Lung CT datasets from six human subjects were used in this study. Each subject was scanned at four time points before and after BAL procedure. Image registration was performed to align images at different time points and different inflation levels. The resulting dense displacement fields were utilized to track tissue volume changes and reveal deformation patterns of local parenchymal tissue quantitatively. The registration accuracy was assessed by measuring landmark matching errors, which were on the order of 1 mm. The results show that quantitative-assessed fluid volume agreed well with bronchoscopist-reported unretrieved BAL volume in the whole lungs (squared linear correlation coefficient was 0.81. The average difference of lung tissue volume at baseline and after 24 hours was around 2%, which indicates that BAL fluid in the lungs was almost absorbed after 24 hours. Regional lung-function changes correlated with the presence of BAL fluid, and regional function returned to baseline as the fluid was reabsorbed.

Association Between RT-Induced Changes in Lung Tissue Density and Global Lung Function

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Ma Jinli; Zhang Junan; Zhou Sumin; Hubbs, Jessica L.; Foltz, Rodney J.; Hollis, Donna R.; Light, Kim L.; Wong, Terence Z.; Kelsey, Christopher R.; Marks, Lawrence B.

2009-01-01

Purpose: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). Methods and Materials: Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. Results: Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. Conclusion: We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.

The thin-section CT, pathological and clinical findings of peripheral small squamous cell lung carcinomas

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Yamamoto, Takahito; Saito, Haruhiro; Kondo, Tetsuro

2010-01-01

We analyzed thin-section CT, pathological, and clinical findings of peripheral lung squamous cell carcinomas, with diameters of less than 20 mm and compared these findings with solid type adenocarcinomas. CT findings of polygonal shapes, notches, pleural thickness, and cavities are more frequently found in squamous cell carcinomas than in adenocarcinomas. The pathological types can be classified in two groups: Solid types, Scirrhous types. The 5 year survival rate after resection is 64.5%, which is poorer than survival rate for solid type adenocarcinomas. It is vital to diagnose and treat peripheral squamous cell carcinomas as early as possible. (author)

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.

Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

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Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

2010-01-01

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

Repeated intratracheal instillation of PM10 induces lipid reshaping in lung parenchyma and in extra-pulmonary tissues.

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Angela Maria Rizzo

Full Text Available Adverse health effects of air pollution attributed mainly to airborne particulate matter have been well documented in the last couple of decades. Short term exposure, referring to a few hours exposure, to high ambient PM10 concentration is linked to increased hospitalization rates for cardiovascular events, typically 24 h after air pollution peaks. Particulate matter exposure is related to pulmonary and cardiovascular diseases, with increased oxidative stress and inflammatory status. Previously, we have demonstrated that repeated intratracheal instillation of PM10sum in BALB/c mice leads to respiratory tract inflammation, creating in lung a condition which could potentially evolve in a systemic toxic reaction. Additionally, plasma membrane and tissue lipids are easily affected by oxidative stress and directly correlated with inflammatory products. With this aim, in the present investigation using the same model, we analyzed the toxic potential of PM10sum exposure on lipid plasma membrane composition, lipid peroxidation and the mechanisms of cells protection in multiple organs such as lung, heart, liver and brain. Obtained results indicated that PM10 exposure led to lung lipid reshaping, in particular phospholipid and cholesterol content increases; concomitantly, the generation of oxidative stress caused lipid peroxidation. In liver we found significant changes in lipid content, mainly due to an increase of phosphatidylcholine, and in total fatty acid composition with a more pronounced level of docosahexaenoic acid; these changes were statistically correlated to lung molecular markers. Heart and brain were similarly affected; heart was significantly enriched in triglycerides in half of the PM10sum treated mice. These results demonstrated a direct involvement of PM10sum in affecting lipid metabolism and oxidative stress in peripheral tissues that might be related to the serious systemic air-pollution effects on human health.

HIV-1 phylogenetic analysis shows HIV-1 transits through the meninges to brain and peripheral tissues.

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Lamers, Susanna L; Gray, Rebecca R; Salemi, Marco; Huysentruyt, Leanne C; McGrath, Michael S

2011-01-01

Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

Lung involvement in systemic connective tissue diseases

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Plavec Goran

2008-01-01

Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

Changes in coagulation-fibrinolysis function in alveolar lavage fluid of endotoxemic dogs after partial removal of peripheral leukocytes

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Shun-gang ZHOU

2011-06-01

Full Text Available Objective To observe the effect of partial removal of peripheral leucocytes on the coagulation-fibrinolysis function of alveolar lavage fluid(ALF in endotoxemic dogs,and explore the influence and mechanisms of activated leucocytes on lung injury in endotoxemic dogs.Methods Thirty male mongrel dogs were involved in present study and randomly divided into 3 groups(10 each: LPS group(group L,sham leukocytapheresis group(group S and leukocytapheresis group(group T.Endotoxemic model was reproduced in group L by administration of LPS(2mg/kg,but the animals did not receive leukocytapheresis.Animals in group T received leukocytapheresis using a continuous-flow blood cell separator 12-14 hours after administration of LPS.Animals in group S received sham leukocytapheresis(the end products were transfused back into the dogs at 12-14 hours after administration of LPS.At 36h after administration of LPS,the lung tissues were harvested to obtain ALF,and the levels of neutrophil elastase(NE,soluble thrombomodulin(sTM,activated protein C(APC and plasminogen activator inhibitor-1(PAI-1 in ALF were determined,the expression of thrombomodulin in lung tissue was observed by immunohistochemical staining,while the routine pathological examination and wet/dry ratio of lung tissue were performed.Results The APC level in ALF was significantly higher,while the NE,sTM and PAI-1 levels in ALF and wet/dry ratio of lung tissue were significantly lower in group T than in group L and group S(P < 0.05.Immunohistochemical examination revealed that the expression of thrombomodulin in lung tissue was higher in group T than in group L and group S.No significant difference was found between group L and group S in the indexes mentioned above.Pathological observation showed the incidence of acute lung injury was significantly lower in group T(2/10 than in group L(7/10 and group S(8/10,P < 0.05.Conclusion Partial removal of peripheral leukocytes may lower the level of NE in ALF

Reduced generation of lung tissue-resident memory T cells during infancy.

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Zens, Kyra D; Chen, Jun Kui; Guyer, Rebecca S; Wu, Felix L; Cvetkovski, Filip; Miron, Michelle; Farber, Donna L

2017-10-02

Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults. However, infection during infancy generated markedly fewer lung TRMs, and heterosubtypic protection was reduced compared with adults. Impaired TRM establishment was infant-T cell intrinsic, and infant effectors displayed distinct transcriptional profiles enriched for T-bet-regulated genes. Notably, mouse and human infant T cells exhibited increased T-bet expression after activation, and reduction of T-bet levels in infant mice enhanced lung TRM establishment. Our findings reveal that infant T cells are intrinsically programmed for short-term responses, and targeting key regulators could promote long-term, tissue-targeted protection at this critical life stage. © 2017 Zens et al.

Measurement of lung tissue dynamics in artificially ventilated rats with optical coherence tomography

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Schnabel Christian

2017-09-01

Full Text Available Diseases of lung tissue and the airways become a major task for medical care and health care systems in modern industrial countries in the future. Suitable treatment methods and strategies for lung support and artificial ventilation are of dare need. Besides the obvious importance as life-saving intervention, the effects of usually used over-pressure ventilation onto the sensitive alveolar tissue are insufficiently understood. Therefore, it is of great interest to characterize lung tissue during artificial ventilation at the alveolar level. Those measurements can be used to link micromechanics of alveolar structures to mechanical properties of the whole lung like compliance and resistance measured at the ventilator device. This can be done only in animal experiments due to the fact that imaging techniques used in human diagnostics like CT or MRT fail to resolve alveolar tissue structures. The disadvantage of high-resolution techniques like optical coherence tomography (OCT or intravital microscopy (IVM is the need of a surgical access to the lung due to the limitation in penetration depth of these techniques. Furthermore, imaging dynamic processes with high-resolution imaging techniques during uninterrupted artificial ventilation is a challenging task. In this study, we present a measurement setup for combined imaging of conventional pressure-controlled ventilated rats and the visualization of volume changes of alveolar structures during one cycle of breath. A custom-made OCT system in combination with a triggered scanning algorithm was used to acquire time-resolved 3D OCT image data. Furthermore, this system was combined with a self-adapting autofocus function for intravital microscopy to track the lung surface keeping the tissue in focal plane. The combination of new dynamic measurement modes for OCT and IVM allows new insights into alveolar tissue and will promote the understanding of mechanical behavior during artificial ventilation.

Interstitial lung disease associated with connective tissue diseases

International Nuclear Information System (INIS)

Medina, Yimy F; Restrepo, Jose Felix; Iglesias, Antonio; Ojeda, Paulina; Matiz, Carlos

2007-01-01

An interstitial lung disease (ILD) belongs to a group of diffuse parenchyma lung diseases it should be differentiated from other pathologies among those are idiopathic and ILD associated to connective tissue diseases (CTD) New concepts have been developed in the last years and they have been classified in seven defined subgroups. It has been described the association of each one of these subgroups with CTD. Natural history and other aspects of its treatment is not known completely .For complete diagnose it is required clinical, image and histopathologic approaches. The biopsy lung plays an essential role. It is important to promote and to stimulate the subclasification of each subgroup with the purpose of knowing their natural history directing the treatment and to improve their outcome

Distribution of latex particles in lung and lymph node tissues of rats and dogs

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Mueller, H.L; Muggenburg, B.A.; Gillett, N.A.; Guilmette, R.A.

1988-01-01

The distribution of fluorescent poly sytrene microspheres in different lung compartments, with differing particle numbers within individual lung and lymph node cells was examined In methacrylate-embedded tissue slices. Rat tissues were analyzed at 1, 7 and 13 days after particle instillation, dog tissues at 7 and 13 days. A much higher fraction of particles was seen in the lung interstitium and in lung-associated lymph nodes in dogs than in rats. Particle concentrations in TBLN cells were generally very low in both species, but were high in free alveolar cells after high particle numbers were instilled, and increased from 1 to 13 days, suggesting that alveolar cells with few particles were cleared faster than those wth high ingested particle numbers. (author)

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus

Science.gov (United States)

Sparger, E. E.; Pitt, K. A.

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs. PMID:28384338

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

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C D Eckstrand

Full Text Available Feline immunodeficiency virus (FIV infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN, and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC-associated viral RNA (vRNA by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

Peripheral and central immune cell reservoirs in tissues from asymptomatic cats chronically infected with feline immunodeficiency virus.

Science.gov (United States)

Eckstrand, C D; Sparger, E E; Pitt, K A; Murphy, B G

2017-01-01

Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection. Results reported herein characterize important tissue reservoirs of active viral replication during the late asymptomatic phase by examining biopsied specimens of spleen, mesenteric lymph node (MLN), and intestine from FIV-infected and uninfected control cats. Peripheral blood collected coincident with harvest of tissues demonstrated severe CD4+ T-cell depletion, undetectable plasma viral gag RNA and rarely detectable peripheral blood mononuclear cell (PBMC)-associated viral RNA (vRNA) by real-time PCR. However, vRNA was detectable in all three tissue sites from three of four FIV-infected cats despite the absence of detectable vRNA in plasma. A novel in situ hybridization assay identified B cell lymphoid follicular domains as microanatomical foci of ongoing FIV replication. Additionally, we demonstrated that CD4+ leukocyte depletion in tissues, and CD4+ and CD21+ leukocytes as important cellular reservoirs of ongoing replication. These findings revealed that tissue reservoirs support foci of ongoing viral replication, in spite of highly restricted viral replication in blood. Lentiviral eradication strategies will need address tissue viral reservoirs.

A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

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Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

2017-03-23

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

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Salama, Samir A., E-mail: salama.3@buckeyemail.osu.edu [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751 (Egypt); Department of Pharmacology and GTMR Unit, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); Omar, Hany A. [Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514 (Egypt); Maghrabi, Ibrahim A. [Department of Clinical Pharmacy, College of Clinical Pharmacy, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); AlSaeed, Mohammed S. [Department of Surgery, College of Medicine, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia); EL-Tarras, Adel E. [High Altitude Research Center, Taif University, Al-Haweiah, Taif 21974 (Saudi Arabia)

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

International Nuclear Information System (INIS)

Salama, Samir A.; Omar, Hany A.; Maghrabi, Ibrahim A.; AlSaeed, Mohammed S.; EL-Tarras, Adel E.

2014-01-01

Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

Nonrespiratory lung function

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Isawa, Toyoharu [Tohoku University Research Institute for Chest Disease and Cancer, Sendai (Japan)

1994-07-01

The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo.

Nonrespiratory lung function

International Nuclear Information System (INIS)

Isawa, Toyoharu

1994-01-01

The function of the lungs is primarily the function as a gas exchanger: the venous blood returning to the lungs is arterialized with oxygen in the lungs and the arterialized blood is sent back again to the peripheral tissues of the whole body to be utilized for metabolic oxygenation. Besides the gas exchanging function which we call ''respiratory lung function'' the lungs have functions that have little to do with gas exchange itself. We categorically call the latter function of the lungs as ''nonrespiratory lung function''. The lungs consist of the conductive airways, the gas exchanging units like the alveoli, and the interstitial space that surrounds the former two compartments. The interstitial space contains the blood and lymphatic capillaries, collagen and elastic fibers and cement substances. The conductive airways and the gas exchanging units are directly exposed to the atmosphere that contains various toxic and nontoxic gases, fume and biological or nonbiological particles. Because the conductive airways are equipped with defense mechanisms like mucociliary clearance or coughs to get rid of these toxic gases, particles or locally produced biological debris, we are usually free from being succumbed to ill effects of inhaled materials. By use of nuclear medicine techniques, we can now evaluate mucociliary clearance function, and other nonrespiratory lung functions as well in vivo

Biochemical and morphological changes in rat lung tissue under the influence of external ionizing radiation

International Nuclear Information System (INIS)

Uzlenkova, N.Je.; Mamotyuk, Je.M.; Gusakova, V.A.; Kononenko, O.K.

2006-01-01

Single external x-ray exposure at minimum and mean lethal doses was established to cause a long activation of biochemical processes in the connective tissue of the rat lungs. Morphological and ultrastructure changes in the tissue of the lungs at early terms after x-ray and gamma-radiation exposure were due to development of destructive and degenerative reactions. The long-term changes were characterized by growth of connective tissue and formation of areas of fibrous changes in the structure of the lungs

An analysis of peripheral small lung carcinomas less than 20 mm in diameter in non-adenocarcinomas and carcinoids. Computed tomographic findings based on radiologic-pathologic correlation

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Tanaka, Gaku; Yamada, Kouzo; Oshita, Fumihiro; Nomura, Ikuo; Noda, Kazumasa; Nakayama, Haruhiko; Mitsuda, Aki; Kameda, Youichi; Yamakido, Michio

2000-01-01

With the introduction of computed tomography (CT) for chest screening in recent years, more cases of resected peripheral small lung carcinomas have been reported. Many of these were adenocarcinomas. To focus on CT findings of peripheral non-adenocarcinoma nodules, we performed a retrospective analysis based on radiographic-pathologic correlations. We analyzed CT findings based on the pathology of peripheral small lung carcinomas, excluding the histological type of adenocarcinomas. We compared our findings with those observed in adenocarcinomas. We reviewed 28 peripheral small lung carcinoma nodules less than 20 mm in diameter, including 13 squamous cell carcinomas, 4 small cell carcinomas, 2 adeno- squamous cell carcinomas, 1 large cell carcinoma, and 8 carcinoids. The carcinomas were classified into two different patterns; non-adenocarcinomas excluding carcinoids, and carcinoids. Both were solid-density types on high-resolution CT (HR-CT) images. The HR-CT findings regarding the shape and number of notching, and the presence or absence of ground glass opacity (GGO) were different between non-adenocarcinomas excluding carcinoids and adenocarcinomas. On the other hand, the HR-CT findings regarding spiculations, GGO and pleural indentations, and the absence of bronchial compression were different between carcinoids and adenocarcinomas. The shape characteristics and internal and marginal analysis on HR-CT images can contribute to the differential diagnosis of the histological type of peripheral small lung carcinomas. (author)

CT characteristics of peripheral organizing pneumonia

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Yang, Seong Oh; Choi, Chul Soon; Kim, Myung Joon; Lee, Kyung Soo; Choi, Hyung Sik; Jun, Young Hwan; Park, Yong Koo

1988-01-01

Diagnostic dilemma of persistent mass-forming parenchymal opacity in the lung periphery occurs occasionally in the realm of diagnostic radiology. Until recently, literature on the role of computed tomography in peripheral organizing pneumonia, which is difficult to differentiate from malignancy, has little been published. We experienced one case of pathologically proven organizing pneumonia diagnosed preoperatively by chest CT. When it comes to solitary peripheral mass density in the lung, we think that CT can be proved useful in the diagnosis of benign organizing pneumonia by showing regular and smoothly corrugate margin, peripheral contrast enhancement with inner low density, and air-trapping by intervening normal lung parenchyma.

Procoagulant, tissue factor-bearing microparticles in bronchoalveolar lavage of interstitial lung disease patients: an observational study.

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Federica Novelli

Full Text Available Coagulation factor Xa appears involved in the pathogenesis of pulmonary fibrosis. Through its interaction with protease activated receptor-1, this protease signals myofibroblast differentiation in lung fibroblasts. Although fibrogenic stimuli induce factor X synthesis by alveolar cells, the mechanisms of local posttranslational factor X activation are not fully understood. Cell-derived microparticles are submicron vesicles involved in different physiological processes, including blood coagulation; they potentially activate factor X due to the exposure on their outer membrane of both phosphatidylserine and tissue factor. We postulated a role for procoagulant microparticles in the pathogenesis of interstitial lung diseases. Nineteen patients with interstitial lung diseases and 11 controls were studied. All subjects underwent bronchoalveolar lavage; interstitial lung disease patients also underwent pulmonary function tests and high resolution CT scan. Microparticles were enumerated in the bronchoalveolar lavage fluid with a solid-phase assay based on thrombin generation. Microparticles were also tested for tissue factor activity. In vitro shedding of microparticles upon incubation with H₂O₂ was assessed in the human alveolar cell line, A549 and in normal bronchial epithelial cells. Tissue factor synthesis was quantitated by real-time PCR. Total microparticle number and microparticle-associated tissue factor activity were increased in interstitial lung disease patients compared to controls (84±8 vs. 39±3 nM phosphatidylserine; 293±37 vs. 105±21 arbitrary units of tissue factor activity; mean±SEM; p<.05 for both comparisons. Microparticle-bound tissue factor activity was inversely correlated with lung function as assessed by both diffusion capacity and forced vital capacity (r² = .27 and .31, respectively; p<.05 for both correlations. Exposure of lung epithelial cells to H₂O₂ caused an increase in microparticle-bound tissue factor

Early structural changes in sheep lung following thoracic irradiation

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Guerry-Force, M.L.; Perkett, E.A.; Brigham, K.L.; Meyrick, B.

1988-01-01

Using a large animal model of radiation lung injury--the sheep exposed to bilateral thoracic irradiation--we have recently shown the development of sustained pulmonary hypertension during the first 4 weeks following radiation. This is the period prior to the onset of pneumonitis and pulmonary fibrosis. In the present study, we have examined biopsy and autopsy lung tissue from these same sheep and assessed the sequential changes in lung morphology. Six unanesthetized sheep received bilateral thoracic irradiation (a total of 15 Gy); control sheep were sham irradiated. Lung biopsy tissue was taken prior to and at weekly or biweekly intervals during the 4 weeks immediately following radiation. The lungs were also removed at autopsy for light and electron microscopic examination. Our results show early (Week 1) interstitial and progressive intraalveolar edema accompanied by endothelial and epithelial injury. A gradual increase in number of interstitial mononuclear cells was evident from Week 1, both in the lung tissue and in perivascular cuffs. The number of peripheral lung interstitial mononuclear cells was twice baseline from Week 3 and included accumulation of lymphocytes, fibroblasts, and intravascular macrophages. The increased numbers of mononuclear cells paralleled the development of chronic pulmonary hypertension, perhaps suggesting their involvement in the pathogenesis of this disease. Alternatively, it may be that increased mononuclear cell number represents a stage of lung repair

Metal concentrations in homing pigeon lung tissue as a biomonitor of atmospheric pollution.

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Cui, Jia; Halbrook, Richard S; Zang, Shuying; Han, Shuang; Li, Xinyu

2018-03-01

Atmospheric pollution in urban areas is a major worldwide concern with potential adverse impacts on wildlife and humans. Biomonitoring can provide direct evidence of the bioavailability and bioaccumulation of toxic metals in the environment that is not available with mechanical air monitoring. The current study continues our evaluation of the usefulness of homing pigeon lung tissue as a biomonitor of atmospheric pollution. Homing pigeons (1-2, 5-6, and 9-10+ year old (yo)) collected from Guangzhou during 2015 were necropsied and concentrations of cadmium (Cd), lead (Pb), and mercury (Hg) were measured in lung tissue. Lung Cd and Pb concentrations were significantly greater in 9-10+-year-old pigeons compared with those in other age groups, indicating their bioavailability and bioaccumulation. Lung Pb and Cd concentrations measured in 5-yo pigeons collected from Guangzhou during 2015 were significantly lower than concentrations reported in 5-yo homing pigeons collected from Guangzhou during 2011 and correlated with concentrations measured using mechanical air monitoring. In addition to temporal differences, spatial differences in concentrations of Cd, Pb, and Hg reported in ambient air samples and in pigeon lung tissues collected from Beijing and Guangzhou are discussed.

Actinomycetoma in arm disseminated to lung with grains of Nocardia brasiliensis with peripheral filaments.

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Muñoz-Hernández, Bertha; Noyola, María Cecilia; Palma-Cortés, Gabriel; Rosete, Dora Patricia; Galván, Miguel Angel; Manjarrez, María Eugenia

2009-07-01

Actinomycetomas represent 97.8% of mycetomas in Mexico, where 86.6% are produced by Nocardia brasiliensis. We report a case of actinomycetoma in the arm by Nocardia brasiliensis disseminated to lung. Uncommon grains were observed which present outside peripheral filaments and also numerous filaments loosing the grains. These characteristics of the grains are due probably because for the long treatment with antibiotics of the patient. In situ antibiotic action against the microcolonies is discussed.

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.

Ectopic Intrathoracic Hepatic Tissue and Accessory Lung Lobe Aplasia in a Dog.

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Lande, Rachel; Dvorak, Laura; Gardiner, David W; Bahr, Anne

2015-01-01

A 6 yr old male Yorkshire terrier was presented for an ~6 yr history of progressive cough and dyspnea. Thoracic radiographs revealed a 6 cm diameter mass within the right caudal thorax. Thoracic ultrasound identified an intrathoracic mass ultrasonographically consistent with liver tissue and a chronic diaphragmatic hernia was suspected. Exploratory laparotomy was performed, but no evidence of a diaphragmatic hernia was identified. Thoracic exploration identified abnormal lung parenchyma. The accessory lung lobe was removed using a stapling devise near its base. The consolidated mass had the gross appearance of liver and was histologically identified as ectopic hepatic tissue. Ectopic hepatic tissue, unlike ectopic splenic and pancreatic tissue, is rare and generally has a subdiaphragmatic distribution. This solitary case report demonstrates that ectopic intrathoracic hepatic tissue should be considered a differential diagnosis for a caudal mediastinal mass.

Stages of the recognition and roentgenological semiotics of minimal peripheric lung cancer

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Lindenbraten, L.D.

1987-01-01

The system of diagnosis of peripheral cancer should be aimed at its detection at stage TI m , i.e. at the detection of a tumor whose shadow on a radiogram 70x70 mm was within 0.5-1.5 cm, and on a plain chest X-ray it was within. Fluorographic and roentgenographic semiotics of minimal peripheral cancer was considered on 40 cases. it was pointed out that the diagnosis of early stages of tumor development could be made only by improving the organizational basis of mass screening by setting up consultative cancer pulmonological commissions. Physicians should be aware of minimum changes in the pulmonary tissue

Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration.

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Chang, Wei; Shah, Munish B; Lee, Paul; Yu, Xiaojun

2018-06-01

Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve

Variable tidal volumes improve lung protective ventilation strategies in experimental lung injury.

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Spieth, Peter M; Carvalho, Alysson R; Pelosi, Paolo; Hoehn, Catharina; Meissner, Christoph; Kasper, Michael; Hübler, Matthias; von Neindorff, Matthias; Dassow, Constanze; Barrenschee, Martina; Uhlig, Stefan; Koch, Thea; de Abreu, Marcelo Gama

2009-04-15

Noisy ventilation with variable Vt may improve respiratory function in acute lung injury. To determine the impact of noisy ventilation on respiratory function and its biological effects on lung parenchyma compared with conventional protective mechanical ventilation strategies. In a porcine surfactant depletion model of lung injury, we randomly combined noisy ventilation with the ARDS Network protocol or the open lung approach (n = 9 per group). Respiratory mechanics, gas exchange, and distribution of pulmonary blood flow were measured at intervals over a 6-hour period. Postmortem, lung tissue was analyzed to determine histological damage, mechanical stress, and inflammation. We found that, at comparable minute ventilation, noisy ventilation (1) improved arterial oxygenation and reduced mean inspiratory peak airway pressure and elastance of the respiratory system compared with the ARDS Network protocol and the open lung approach, (2) redistributed pulmonary blood flow to caudal zones compared with the ARDS Network protocol and to peripheral ones compared with the open lung approach, (3) reduced histological damage in comparison to both protective ventilation strategies, and (4) did not increase lung inflammation or mechanical stress. Noisy ventilation with variable Vt and fixed respiratory frequency improves respiratory function and reduces histological damage compared with standard protective ventilation strategies.

Overall and peripheral lung function assessment by spirometry and forced oscillation technique in relation to asthma diagnosis and control.

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Heijkenskjöld Rentzhog, C; Janson, C; Berglund, L; Borres, M P; Nordvall, L; Alving, K; Malinovschi, A

2017-12-01

Classic spirometry is effort dependent and of limited value in assessing small airways. Peripheral airway involvement, and relation to poor control, in asthma, has been highlighted recently. Forced oscillation technique (FOT) offers an effort-independent assessment of overall and peripheral lung mechanics. We studied the association between lung function variables, obtained either by spirometry or multifrequency (5, 11 and 19 Hz) FOT, and asthma diagnosis and control. Spirometry measures, resistance at 5 (R5) and 19 Hz (R19), reactance at 5 Hz (X5), resonant frequency (f res ), resistance difference between 5-19 Hz (R5-R19) and Asthma Control Test scores were determined in 234 asthmatic and 60 healthy subjects (aged 13-39 years). We used standardized lung function variables in logistic regression analyses, unadjusted and adjusted for age, height, gender and weight. Lower FEV 1 /FVC (OR [95% CI] 0.47 [0.32, 0.69]) and FEF 50 (0.62 [0.46, 0.85]) per standard deviation increase, and higher R5 (3.31 [1.95, 5.62]) and R19 (2.54 [1.65, 3.91]) were associated with asthma diagnosis. Independent predictive effects of FEV 1 /FVC and R5 or R19, respectively, were found for asthma diagnosis. Lower FEV 1 /FVC and altered peripheral FOT measures (X5, f res and R5-R19) were associated with uncontrolled asthma (P-values < .05). Resistance FOT measures were equally informative as spirometry, related to asthma diagnosis, and, furthermore, offered additive information to FEV 1 /FVC, supporting a complementary role for FOT. Asthma control was related to FOT measures of peripheral airways, suggesting a potential use in identifying such involvement. Further studies are needed to determine a clinical value and relevant reference values in children, for the multifrequency FOT measurements. © 2017 John Wiley & Sons Ltd.

Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats.

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Dronjak, S; Gavrilovic, L

2006-06-01

Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days) and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4 degrees C, 2 h), were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(3H-methyl)-methionine was used. The O-methylated derivatives were oxidized to 3H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18%) and hippocampal dopamine (about 20%) stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39%) in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20%) as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

Effects of stress on catecholamine stores in central and peripheral tissues of long-term socially isolated rats

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Dronjak S.

2006-01-01

Full Text Available Both the peripheral sympatho-adrenomedullary and central catecholaminergic systems are activated by various psycho-social and physical stressors. Catecholamine stores in the hypothalamus, hippocampus, adrenal glands, and heart auricles of long-term socially isolated (21 days and control 3-month-old male Wistar rats, as well as their response to immobilization of all 4 limbs and head fixed for 2 h and cold stress (4ºC, 2 h, were studied. A simultaneous single isotope radioenzymatic assay based on the conversion of catecholamines to the corresponding O-methylated derivatives by catechol-O-methyl-transferase in the presence of S-adenosyl-l-(³H-methyl-methionine was used. The O-methylated derivatives were oxidized to ³H-vanilline and the radioactivity measured. Social isolation produced depletion of hypothalamic norepinephrine (about 18% and hippocampal dopamine (about 20% stores and no changes in peripheral tissues. Immobilization decreased catecholamine stores (approximately 39% in central and peripheral tissues of control animals. However, in socially isolated rats, these reductions were observed only in the hippocampus and peripheral tissues. Cold did not affect hypothalamic catecholamine stores but reduced hippocampal dopamine (about 20% as well as norepinephrine stores in peripheral tissues both in control and socially isolated rats, while epinephrine levels were unchanged. Thus, immobilization was more efficient in reducing catecholamine stores in control and chronically isolated rats compared to cold stress. The differences in rearing conditions appear to influence the response of adult animals to additional stress. In addition, the influence of previous exposure to a stressor on catecholaminergic activity in the brainstem depends on both the particular catecholaminergic area studied and the properties of additional acute stress. Therefore, the sensitivity of the catecholaminergic system to habituation appears to be tissue-specific.

[Effect of oxidative stress-associated damage to the lung tissue caused by different body mass index in the rat models].

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Li, X Y; Zhang, X J; Zhao, J H; Xu, J Y

2016-12-12

Objective: To investigate the influence of different diets on serum protein expression levels of 4-hydroxynonenal (4-HNE), thioredoxin (Trx), thioredoxin reductase (TrxR) and the activities of Trx and TrxR, and to explore the effect of damage to the lung tissue and the underlying mechanisms of different body mass index caused by different diets in the rat models . Method: Healthy clean male SD rats were randomly divided into normal group, emaciation group and fat group, which were raised by different diets for 6 months.Then the rats were sacrificed and the serum and lung tissue were prepared. The levels of 4-HNE, Trx and TrxR in peripheral blood were quantitatively analyzed by enzyme-linked immunosorbent assay(ELISA), and the activities of Trx and TrxR were measured by chemical methods. Results: Compared with the normal group, the lung tissue had more apparent emphysema in the emaciation and the fat groups under light microscope, and more inflammatory cell infiltration in alveolar septum was observed in the fat group.The levels of 4-HNE in the fat group[(24.7±8.7)mg/L]was significantly higher than that in the normal group[(15.4±4.7)mg/L, P 0.05)in the levels of 4-HNE between the emaciation and the normal groups. The levels of TrxR in the emaciation group[(7.7±1.4)μg/ml]was significantly higher than that in the normal and the fat groups[(6.2±1.1), (4.9±1.4)μg/ml, all P 0.05). The activity of Trx in the emaciation group[(32.4±8.5)×10 -3 A ·min -1 ·mg -1 ]was significantly higher than that in the normal group[(19.6±3.3)×10 -3 A ·min -1 ·mg -1 ]and the fat group[(11.3±7.5)×10 -3 A ·min -1 ·mg -1 , all P 0.05). Conclusion: Both high BMI and low BMI can affect the oxidative stress of the body, resulting in increased oxidants and decreased antioxidants, and can cause damage to the lung tissue in the rat models.

Peripheral CLOCK Regulates Target-Tissue Glucocorticoid Receptor Transcriptional Activity in a Circadian Fashion in Man

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Charmandari, Evangelia; Chrousos, George P.; Lambrou, George I.; Pavlaki, Aikaterini; Koide, Hisashi; Ng, Sinnie Sin Man; Kino, Tomoshige

2011-01-01

Context and Objective Circulating cortisol fluctuates diurnally under the control of the “master” circadian CLOCK, while the peripheral “slave” counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR) at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans. Design and Participants We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs) obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs) as non-synchronized controls. Results GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo. Conclusions Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night. PMID:21980503

Peripheral CLOCK regulates target-tissue glucocorticoid receptor transcriptional activity in a circadian fashion in man.

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Evangelia Charmandari

Full Text Available Circulating cortisol fluctuates diurnally under the control of the "master" circadian CLOCK, while the peripheral "slave" counterpart of the latter regulates the transcriptional activity of the glucocorticoid receptor (GR at local glucocorticoid target tissues through acetylation. In this manuscript, we studied the effect of CLOCK-mediated GR acetylation on the sensitivity of peripheral tissues to glucocorticoids in humans.We examined GR acetylation and mRNA expression of GR, CLOCK-related and glucocorticoid-responsive genes in peripheral blood mononuclear cells (PBMCs obtained at 8 am and 8 pm from 10 healthy subjects, as well as in PBMCs obtained in the morning and cultured for 24 hours with exposure to 3-hour hydrocortisone pulses every 6 hours. We used EBV-transformed lymphocytes (EBVLs as non-synchronized controls.GR acetylation was higher in the morning than in the evening in PBMCs, mirroring the fluctuations of circulating cortisol in reverse phase. All known glucocorticoid-responsive genes tested responded as expected to hydrocortisone in non-synchronized EBVLs, however, some of these genes did not show the expected diurnal mRNA fluctuations in PBMCs in vivo. Instead, their mRNA oscillated in a Clock- and a GR acetylation-dependent fashion in naturally synchronized PBMCs cultured ex vivo in the absence of the endogenous glucocorticoid, suggesting that circulating cortisol might prevent circadian GR acetylation-dependent effects in some glucocorticoid-responsive genes in vivo.Peripheral CLOCK-mediated circadian acetylation of the human GR may function as a target-tissue, gene-specific counter regulatory mechanism to the actions of diurnally fluctuating cortisol, effectively decreasing tissue sensitivity to glucocorticoids in the morning and increasing it at night.

Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors

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Chang Thomas

2007-10-01

Full Text Available Abstract Background Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. Methods Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3–5 were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45–60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. Results Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. Conclusion Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.

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.

BATTLE (Biomarker-based Approach of Targeted Therapy for Lung Cancer Elimination)

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2012-04-01

Pathol. Lab. Med. 1977; 101; 216–218. 12. Heilman E, Feiner H. The role of electron microscopy in the diagnosis of unusual peripheral lung tumors...predictor of poor overall sur- ival in both sets. Conclusions. The AP2, which is located in the nucle- plasm in normal lung tissue, is found in either...nucleo- plasm , where its telomere-lengthening activity occurs [2, 3]. In NSCLC patients, hTERT expression has been asso- ciated with lower rates of

A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters.

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Loubani, Osama M; Green, Robert S

2015-06-01

The aim of this study was to collect and describe all published reports of local tissue injury or extravasation from vasopressor administration via either peripheral intravenous (IV) or central venous catheter. A systematic search of Medline, Embase, and Cochrane databases was performed from inception through January 2014 for reports of adults who received vasopressor intravenously via peripheral IV or central venous catheter for a therapeutic purpose. We included primary studies or case reports of vasopressor administration that resulted in local tissue injury or extravasation of vasopressor solution. Eighty-five articles with 270 patients met all inclusion criteria. A total of 325 separate local tissue injury and extravasation events were identified, with 318 events resulting from peripheral vasopressor administration and 7 events resulting from central administration. There were 204 local tissue injury events from peripheral administration of vasopressors, with an average duration of infusion of 55.9 hours (±68.1), median time of 24 hours, and range of 0.08 to 528 hours. In most of these events (174/204, 85.3%), the infusion site was located distal to the antecubital or popliteal fossae. Published data on tissue injury or extravasation from vasopressor administration via peripheral IVs are derived mainly from case reports. Further study is warranted to clarify the safety of vasopressor administration via peripheral IVs. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues.

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Baltaci, A K; Mogulkoc, R; Salbacak, A; Celik, I; Sivrikaya, A

2012-01-01

The objective of the present study was to examine the effects of zinc supplementation on the oxidant damage in lung and liver tissues in rats exposed to a 50-Hz frequency magnetic field for 5 minutes every other day over a period of 6 months. The study included 24 adult male Sprague-Dawley rats, which were divided into the three groups in equal numbers: Group 1, the control group (G1); Group 2, the group exposed to an electromagnetic field (G2); and Group 3, the group, which was exposed to an EMF and supplemented with zinc (G3). At the end of the 6-month procedures, the animals were decapitated to collect lung and liver tissue samples, in which MDA was analyzed using the "TBARS method (nmol/g/protein)", GSH by the "biuret method (mg/g/protein)" and zinc levels by atomic emission (µg/dl). MDA levels in lung and liver tissues in G2 were higher than those in G1 and G3, and the levels in G3 were higher than those in G1 (pelectromagnetic field caused cellular damage in lung and liver tissues and zinc supplementation inhibited the inflicted cellular damage. Another important result of this study that needs emphasis was that exposure to an electromagnetic field led to a significant decrease in zinc levels in lung and liver tissues (Tab. 3, Ref. 23).

Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

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Viktor M Pastukh

2011-03-01

Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

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.).

SU-F-T-416: Dosimetric Comparison of Coplanar and Non-Coplanar IMRT Plans for Peripheral Lung Lesion

International Nuclear Information System (INIS)

Kang, J; Zhang, S; Philbrook, S; Paul, S; Wang, B

2016-01-01

Purpose: The purpose of this study was to compare dosimetric parameters of treatment plans between coplanar and non-coplanar techniques for treating peripheral lung lesions. Methods: The planning CT scans of 6 patients in supine positions were used in this study. The size of the PTV ranges from 163 c.c. to 782 c.c.. The locations of PTV are mostly at the peripheral of Lung, some spreading to the mediastinum. For each patient, we generated two IMRT plans, one with and the other without non-coplanar beams. The non-coplanar beams were carefully selected so that the beams would never exit patient bodies through the contralateral lung. The IMRT plans were generated with Pinnacle 9.8 treatment planning software. The IMRT optimization objectives were kept the same for the corresponding pairs of plans. All plans were normalized such that 95% of PTV receives the prescription dose (full dose). Results: The conformity index (mean±standard deviation of the mean) is 1.49±0.14 and 1.58±0.23 for the coplanar and noncoplanar plans, respectively. The heterogeneity index (mean±standard deviation of the mean) is 7.74 ±2.33 and 6.34±1.40 for the coplanar and non-coplanar plans, respectively. The maximum heart dose is 60.94±6.22 and 60.42±7.21 Gy, and mean heart dose is 10.22 ±7.57, 9.07 ±6.32 Gy, for the coplanar and non-coplanar plans, respectively. The ipsilateral lung V20 is 48.0%±2.4% and 47.5%±3.3%, and V5 is 68.2%±10.0% and 69.1%±7.3%, for the coplanar and noncoplanar plans, respectively. Furthermore, with the non-coplanar beam arrangement, the contralateral lung V20 was reduced from 3.3%±3.7% to 1.3%±0.8%, and the contralateral Lung V5 is reduced significantly from 65.6%±9.3% to 33.5%±20.9% (p value =0.008). Conclusion: The IMRT plans with non-coplanar beam arrangement could reduce the exit dose to the contralateral lung, and therefore reduce the contralateral lung V5 significantly. This method is especially helpful while the lung lesion doesn’t have a

A morphological study of bronchi and lung tissues in long-term survived dogs

OpenAIRE

松本, 伸

1984-01-01

Morphological changes of the bronchus and lung tissue of ten adult dogs were examined at various intervals after sleeve resection of the left upper lobe was performed in combination with bronchoplasty and pulmonary artery angioplasty. Postoperative changes in the bronchus and pulmonary artery were investigated by bronchoscopy and pulmonary angiography 8 months to 14 months after the operation. The dogs were sacrificed 9 months to 32 months after the operation, and the bronchus and lung tissue...

Expression and Significance of gp96 and Immune-related Gene CTLA-4, CD8 in Lung Cancer Tissues

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Haiyan ZHENG

2010-08-01

Full Text Available Background and objective It has been proven that gp96 plays an important role in specific cytotoxic immune response which is involved in anti-tumor effect in the body. The aim of this study is to investigate the biological significance of heat shock protein gp96 and immune-related gene CTLA-4, CD8 expressions in lung cancer tissues of different progressive stages. Methods We used Envision immunohistochemistry method to detect the levels of expression of gp96, CTLA-4, CD8 in tissue microarray, which contained 89 primary lung cancer tissues, 12 lymph node metastasis lung cancer tissues, 12 precancerous lesions and 10 normal lung tissues, and analyzed the relationship between their expressions and clinicopathological parameters. Results (1 The positive rate of gp96 in primary lung cancer was remarkably higher than that in precancerous lesion and normal lung tissue (P < 0.05. The positive rate of CTLA-4 in primary lung cancer tissue and precancerous lesion was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of CD8 in primary lung cancer tissue was significantly higher than that in normal lung tissue (P < 0.05. The positive rate of gp96 in CD8-positive lymphocytes in the high expression group was less than that in the low group (P < 0.05. (2 The positive rate of gp96 was closely related to sex, differentiation and clinical stage (P < 0.05, but not to age, gross type, histological type and lymph node metastasis (P > 0.05. The positive rate of CTLA-4 was closely related to age and differentiation (P < 0.05, but not to sex, gross type, histological type, clinical stage and lymph node metastasis (P > 0.05. CD8 expression was related to clinical stage (P < 0.05, but not to sex, age, gross type, histological type, differentiation and lymph node metastasis (P > 0.05. The positive rates of gp96, CTLA-4 were higher than that of CD8 in squamous cell carcinoma and SCLC, respectively. (3 There was positive correlation between gp

Progress in Tissue Specimens Alternative for the Driver Genes Testing of Non-small Cell Lung Cancer

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Yan SUN

2015-06-01

Full Text Available Target treatment based on driver genes in advanced non-small cell lung cancer is very important currently. Tumor tissues is the gold standard for driver genes testing. However, most of patients could not get the gene information for lack of enough tissues. To explore the tissue specimens alternatives is a hot spot in clinical work. This report reviews the tissue specimen alternatives of driver gene testing in non-small cell lung cancer.

Synovial tissue heterogeneity in rheumatoid arthritis in relation to disease activity and biomarkers in peripheral blood

NARCIS (Netherlands)

van Baarsen, Lisa G. M.; Wijbrandts, Carla A.; Timmer, Trieneke C. G.; van der Pouw Kraan, Tineke C. T. M.; Tak, Paul P.; Verweij, Cornelis L.

2010-01-01

OBJECTIVE: To investigate the clinical relevance of synovial tissue subtypes in rheumatoid arthritis (RA) and to search for peripheral blood (PB) markers that may serve as biomarkers for tissue subtypes. METHODS: Gene expression analysis using complementary DNA microarrays was applied on paired

Sympathetic reflex control of blood flow in human peripheral tissues

DEFF Research Database (Denmark)

Henriksen, O

1991-01-01

Sympathetic vasoconstrictor reflexes are essential for the maintenance of arterial blood pressure in upright position. It has been generally believed that supraspinal sympathetic vasoconstrictor reflexes elicited by changes in baroreceptor activity play an important role. Recent studies on human...... sympathetic vasoconstrictor reflexes are blocked. Blood flow has been measure by the local 133Xe-technique. The results indicate the presence of spinal as well as supraspinal sympathetic vasoconstrictor reflexes to human peripheral tissues. Especially is emphasized the presence of a local sympathetic veno...... skeletal muscle, cutaneous and subcutaneous tissues of the limbs indicate that the situation is more complex. Measurements have been carried out during acute as well as chronic sympathetic denervation. Spinal sympathetic reflex mechanisms have been evaluated in tetraplegic patients, where supraspinal...

Losartan Attenuates Degradation of Aorta and Lung Tissue Micromechanics in a Mouse Model of Severe Marfan Syndrome.

Science.gov (United States)

Lee, Jia-Jye; Galatioto, Josephine; Rao, Satish; Ramirez, Francesco; Costa, Kevin D

2016-10-01

Marfan syndrome (MFS) is an autosomal dominant disease of the connective tissue due to mutations in the fibrillin-1 gene (FBN1). This study aimed at characterizing microelastic properties of the ascending aortic wall and lung parenchyma tissues from wild type (WT) and age-matched Fbn1 hypomorphic mice (Fbn1(mgR/mgR) mice) to identify tissue-specific biomechanical effects of aging and disease in MFS. Atomic force microscopy was used to indent lung parenchyma and aortic wall tissues, using Hybrid Eshelby Decomposition analysis to extract layer-specific properties of the intima and media. The intima stiffened with age and was not different between WT and Fbn1(mgR/mgR) tissues, whereas the media layer of MFS aortas showed progressive structural and mechanical degradation with a modulus that was 50% softer than WT by 3.5 months of age. Similarly, MFS mice displayed progressive structural and mechanical deterioration of lung tissue, which was over 85% softer than WT by 3.5 months of age. Chronic treatment with the angiotensin type I receptor antagonist, losartan, attenuated the aorta and lung tissue degradation, resulting in structural and mechanical properties not significantly different from age-matched WT controls. By revealing micromechanical softening of elastin-rich aorta and lung tissues with disease progression in fibrillin-1 deficient mice, our findings support the use of losartan as a prophylactic treatment that may abrogate the life-threatening symptoms of MFS.

Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

Science.gov (United States)

Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

2013-10-01

Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality. Copyright © 2013 Elsevier GmbH. All rights reserved.

Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry.

Science.gov (United States)

Christensen, Gary E; Song, Joo Hyun; Lu, Wei; El Naqa, Issam; Low, Daniel A

2007-06-01

Breathing motion is one of the major limiting factors for reducing dose and irradiation of normal tissue for conventional conformal radiotherapy. This paper describes a relationship between tracking lung motion using spirometry data and image registration of consecutive CT image volumes collected from a multislice CT scanner over multiple breathing periods. Temporal CT sequences from 5 individuals were analyzed in this study. The couch was moved from 11 to 14 different positions to image the entire lung. At each couch position, 15 image volumes were collected over approximately 3 breathing periods. It is assumed that the expansion and contraction of lung tissue can be modeled as an elastic material. Furthermore, it is assumed that the deformation of the lung is small over one-fifth of a breathing period and therefore the motion of the lung can be adequately modeled using a small deformation linear elastic model. The small deformation inverse consistent linear elastic image registration algorithm is therefore well suited for this problem and was used to register consecutive image scans. The pointwise expansion and compression of lung tissue was measured by computing the Jacobian of the transformations used to register the images. The logarithm of the Jacobian was computed so that expansion and compression of the lung were scaled equally. The log-Jacobian was computed at each voxel in the volume to produce a map of the local expansion and compression of the lung during the breathing period. These log-Jacobian images demonstrate that the lung does not expand uniformly during the breathing period, but rather expands and contracts locally at different rates during inhalation and exhalation. The log-Jacobian numbers were averaged over a cross section of the lung to produce an estimate of the average expansion or compression from one time point to the next and compared to the air flow rate measured by spirometry. In four out of five individuals, the average log

Tracking lung tissue motion and expansion/compression with inverse consistent image registration and spirometry

International Nuclear Information System (INIS)

Christensen, Gary E.; Song, Joo Hyun; Lu, Wei; Naqa, Issam El; Low, Daniel A.

2007-01-01

Breathing motion is one of the major limiting factors for reducing dose and irradiation of normal tissue for conventional conformal radiotherapy. This paper describes a relationship between tracking lung motion using spirometry data and image registration of consecutive CT image volumes collected from a multislice CT scanner over multiple breathing periods. Temporal CT sequences from 5 individuals were analyzed in this study. The couch was moved from 11 to 14 different positions to image the entire lung. At each couch position, 15 image volumes were collected over approximately 3 breathing periods. It is assumed that the expansion and contraction of lung tissue can be modeled as an elastic material. Furthermore, it is assumed that the deformation of the lung is small over one-fifth of a breathing period and therefore the motion of the lung can be adequately modeled using a small deformation linear elastic model. The small deformation inverse consistent linear elastic image registration algorithm is therefore well suited for this problem and was used to register consecutive image scans. The pointwise expansion and compression of lung tissue was measured by computing the Jacobian of the transformations used to register the images. The logarithm of the Jacobian was computed so that expansion and compression of the lung were scaled equally. The log-Jacobian was computed at each voxel in the volume to produce a map of the local expansion and compression of the lung during the breathing period. These log-Jacobian images demonstrate that the lung does not expand uniformly during the breathing period, but rather expands and contracts locally at different rates during inhalation and exhalation. The log-Jacobian numbers were averaged over a cross section of the lung to produce an estimate of the average expansion or compression from one time point to the next and compared to the air flow rate measured by spirometry. In four out of five individuals, the average log

Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle,

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Samanta Portão de Carlos

2014-08-01

Full Text Available OBJECTIVE: To evaluate oxidative damage (lipid oxidation, protein oxidation, thiobarbituric acid-reactive substances [TBARS], and carbonylation and inflammation (expression of phosphorylated AMP-activated protein kinase and mammalian target of rapamycin [p-AMPK and p-mTOR, respectively] in the lung parenchyma and diaphragm muscles of male C57BL-6 mice exposed to cigarette smoke (CS for 7, 15, 30, 45, or 60 days. METHODS: Thirty-six male C57BL-6 mice were divided into six groups (n = 6/group: a control group; and five groups exposed to CS for 7, 15, 30, 45, and 60 days, respectively. RESULTS: Compared with control mice, CS-exposed mice presented lower body weights at 30 days. In CS-exposed mice (compared with control mice, the greatest differences (increases in TBARS levels were observed on day 7 in diaphragm-muscle, compared with day 45 in lung tissue; the greatest differences (increases in carbonyl levels were observed on day 7 in both tissue types; and sulfhydryl levels were lower, in both tissue types, at all time points. In lung tissue and diaphragm muscle, p-AMPK expression exhibited behavior similar to that of TBARS. Expression of p-mTOR was higher than the control value on days 7 and 15 in lung tissue, as it was on day 45 in diaphragm muscle. CONCLUSION: Our data demonstrate that CS exposure produces oxidative damage, not only in lung tissue but also (primarily in muscle tissue, having an additional effect on respiratory muscle, as is frequently observed in smokers with COPD.

Poster — Thur Eve — 65: A dosimetric comparison of isocentric and non-isocentric coplanar SBRT VMAT plans for peripheral lung tumours

International Nuclear Information System (INIS)

Conroy, L; Liu, HW; Lau, H; Smith, WL

2014-01-01

Volumetric modulated arc therapy (VMAT) delivers lung sterotactic body radiotherapy (SBRT) in shorter treatment time and less monitor units with comparable coverage and organ at risk sparing compared to conventional SBRT treatments. Isocentric VMAT treatment of peripheral lung tumours occasionally requires couch shifts that can inhibit 360° gantry rotation, resulting in additional imaging shifts for each treatment session, and increased potential for involuntary in-fraction motion. Here, we investigate whether non-isocentric VMAT plans can achieve comparable plan quality to isocentric plans for peripheral lung tumours. Three patient plans were selected with targets displaced > 8.5 cm (range: 8.8 – 9.9 cm) laterally from patient midline. For each patient, a plan with isocentre placed within the target volume (isocentric plan) was created and optimized. The same optimization parameters were then used to create a plan with the isocentre at patient midline (non-isocentric plan). Plan quality was evaluated and compared based on planning target volume (PTV) coverage, high dose spillage, dose homogeneity, intermediate dose spillage, dose fall-off gradient, and organ at risk contraints. Non-isocentric plans of equivalent plan quality to isocentric plans were achieved for all patients by optimizing collimator rotations. Field isocentres can be placed at patient midline, as opposed to inside the target volume, with no significant degradation in VMAT plan quality for lateral tumour displacements up to 10 cm. Non-isocentric treatment of peripheral lung tumours could result in decreased overall treatment session time and eliminate the need for imaging shifts prior to VMAT treatment

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...

Rapid detection of Mannheimia haemolytica in lung tissues of sheep and from bacterial culture

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Jyoti Kumar

2015-09-01

Full Text Available Aim: This study was aimed to detect Mannheimia haemolytica in lung tissues of sheep and from a bacterial culture. Introduction: M. haemolytica is one of the most important and well-established etiological agents of pneumonia in sheep and other ruminants throughout the world. Accurate diagnosis of M. haemolytica primarily relies on bacteriological examination, biochemical characteristics and, biotyping and serotyping of the isolates. In an effort to facilitate rapid M. haemolytica detection, polymerase chain reaction assay targeting Pasteurella haemolytica serotype-1 specific antigens (PHSSA, Rpt2 and 12S ribosomal RNA (rRNA genes were used to detect M. haemolytica directly from lung tissues and from bacterial culture. Materials and Methods: A total of 12 archived lung tissues from sheep that died of pneumonia on an organized farm were used. A multiplex polymerase chain reaction (mPCR based on two-amplicons targeted PHSSA and Rpt2 genes of M. haemolytica were used for identification of M. haemolytica isolates in culture from the lung samples. All the 12 lung tissue samples were tested for the presence M. haemolytica by PHSSA and Rpt2 genes based PCR and its confirmation by sequencing of the amplicons. Results: All the 12 lung tissue samples tested for the presence of PHSSA and Rpt2 genes of M. haemolytica by mPCR were found to be positive. Amplification of 12S rRNA gene fragment as internal amplification control was obtained with each mPCR reaction performed from DNA extracted directly from lung tissue samples. All the M. haemolytica were also positive for mPCR. No amplified DNA bands were observed for negative control reactions. All the three nucleotide sequences were deposited in NCBI GenBank (Accession No. KJ534629, KJ534630 and KJ534631. Sequencing of the amplified products revealed the identity of 99-100%, with published sequence of PHSSA and Rpt2 genes of M. haemolytica available in the NCBI database. Sheep specific mitochondrial 12S r

Development of an experimental model of brain tissue heterotopia in the lung

Science.gov (United States)

Quemelo, Paulo Roberto Veiga; Sbragia, Lourenço; Peres, Luiz Cesar

2007-01-01

Summary The presence of heterotopic brain tissue in the lung is a rare abnormality. The cases reported thus far are usually associated with neural tube defects (NTD). As there are no reports of experimental models of NTD that present this abnormality, the objective of the present study was to develop a surgical method of brain tissue heterotopia in the lung. We used 24 pregnant Swiss mice divided into two groups of 12 animals each, denoted 17GD and 18GD according to the gestational day (GD) when caesarean section was performed to collect the fetuses. Surgery was performed on the 15th GD, one fetus was removed by hysterectomy and its brain tissue was cut into small fragments and implanted in the lung of its litter mates. Thirty-four live fetuses were obtained from the 17GD group. Of these, eight (23.5%) were used as control (C), eight (23.5%) were sham operated (S) and 18 (52.9%) were used for pulmonary brain tissue implantation (PBI). Thirty live fetuses were obtained from the females of the 18GD group. Of these, eight (26.6%) were C, eight (26.6%) S and 14 (46.6%) were used for PBI. Histological examination of the fetal trunks showed implantation of GFAP-positive brain tissue in 85% of the fetuses of the 17GD group and in 100% of those of the 18GD group, with no significant difference between groups for any of the parameters analysed. The experimental model proved to be efficient and of relatively simple execution, showing complete integration of the brain tissue with pulmonary and pleural tissue and thus representing a model that will permit the study of different aspects of cell implantation and interaction. PMID:17877535

X-ray semiotics of radiations affections of the lungs

International Nuclear Information System (INIS)

Rabinovich, R.M.; Shapiro, I.V.

1976-01-01

On the hasis of analysis of roentgenograms, tomograms, and bronchograms in 189 patients a repeated study was made of the X-ray semiotics of radiation affections of the lungs. The leading roentgenological symptom of radiation affections of the lungs irrespective of their primary localization, was linear deformity and intensification of the broncho-vascular patten in the peripheral zone. This was expressed on roentgenograms in the form of radially- and cross- coursing shadows from the root: tomog.raphically it was manifested in narrowed shadows of the vessels, a change of their course, their approximation and a tendency to approach the centre; analogous disturbances of topography of the bronchi with phenomena of deforming bronchitis were seen in bronchography. A significant si.gn of radiation injuries of the lung tissue is a tendency to progressive development of connective tissue, which was expressed roentgenologically in extensive pneumosclerosis, sometimes with an outcome into fibrothorax with marked topographic disturbances. Radiation injuries are accompanied by an adhesive reaction of the pleura

Porcine endogenous retroviral nucleic acid in peripheral tissues is associated with migration of porcine cells post islet transplant.

Science.gov (United States)

Binette, Tanya M; Seeberger, Karen L; Lyon, James G; Rajotte, Ray V; Korbutt, Gregory S

2004-07-01

Porcine islets represent an alternative source of insulin-producing tissue, however, porcine endogenous retrovirus (PERV) remains a concern. In this study, SCID mice were transplanted with nonencapsulated (non-EC), microencapsulated (EC) or macroencapsulated (in a TheraCyte trade mark device) neonatal porcine islets (NPIs), and peripheral tissues were screened for presence of viral DNA and mRNA. To understand the role of an intact immune system in PERV incidence, mice with established NPI grafts were reconstituted with splenocytes. Peripheral tissues were screened for PERV and porcine DNA using PCR. Tissues with positive DNA were analyzed for PERV mRNA using RT-PCR. No significant difference was observed between non-EC and EC transplants regarding presence of PERV or porcine-specific DNA or mRNA. In reconstituted animals, little PERV or porcine DNA, and no PERV mRNA was detected. No PERV or porcine-specific DNA was observed in animals implanted with a TheraCyte trade mark device. In conclusion, an intact immune system significantly lowered the presence of PERV. Microencapsulation of islets did not alter PERV presence, however, macroencapsulation in the TheraCyte device did. Lower PERV incidence coincided with lower porcine DNA in peripheral tissues, linking the presence of PERV to migration of porcine cells.

Correlation of MLH1 and MGMT methylation levels between peripheral blood leukocytes and colorectal tissue DNA samples in colorectal cancer patients.

Science.gov (United States)

Li, Xia; Wang, Yibaina; Zhang, Zuoming; Yao, Xiaoping; Ge, Jie; Zhao, Yashuang

2013-11-01

CpG island methylation in the promoter regions of the DNA mismatch repair gene mutator L homologue 1 ( MLH1 ) and DNA repair gene O 6 -methylguanine-DNA methyltransferase ( MGMT ) genes has been shown to occur in the leukocytes of peripheral blood and colorectal tissue. However, it is unclear whether the methylation levels in the blood leukocytes and colorectal tissue are correlated. The present study analyzed and compared the levels of MGMT and MLH1 gene methylation in the leukocytes of peripheral blood and colorectal tissues obtained from patients with colorectal cancer (CRC). The methylation levels of MGMT and MLH1 were examined using methylation-sensitive high-resolution melting (MS-HRM) analysis. A total of 44 patients with CRC were selected based on the MLH1 and MGMT gene methylation levels in the leukocytes of the peripheral blood. Corresponding colorectal tumor and normal tissues were obtained from each patient and the DNA methylation levels were determined. The correlation coefficients were evaluated using Spearman's rank test. Agreement was determined by generalized κ-statistics. Spearman's rank correlation coefficients (r) for the methylation levels of the MGMT and MLH1 genes in the leukocytes of the peripheral blood and normal colorectal tissue were 0.475 and 0.362, respectively (P=0.001 and 0.016, respectively). The agreement of the MGMT and MLH1 gene methylation levels in the leukocytes of the peripheral blood and normal colorectal tissue were graded as fair and poor (κ=0.299 and 0.126, respectively). The methylation levels of MGMT and MLH1 were moderately and weakly correlated between the patient-matched leukocytes and the normal colorectal tissue, respectively. Blood-derived DNA methylation measurements may not always represent the levels of normal colorectal tissue methylation.

Proteomic Analysis of Lung Tissue in a Rat Acute Lung Injury Model: Identification of PRDX1 as a Promoter of Inflammation

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Dongdong Liu

2014-01-01

Full Text Available Acute respiratory distress syndrome (ARDS remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6, interleukin-8 (IL-8, and tumor necrosis factor-α (TNF-α, whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation.

Science.gov (United States)

Solleti, Siva Kumar; Srisuma, Sorachai; Bhattacharya, Soumyaroop; Rangel-Moreno, Javier; Bijli, Kaiser M; Randall, Troy D; Rahman, Arshad; Mariani, Thomas J

2016-07-01

Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin. Although SERPINE2 is a candidate susceptibility gene for chronic obstructive pulmonary disease, the physiologic role of this protease inhibitor in lung development and homeostasis is unknown. We observed spontaneous monocytic-cell infiltration in the lungs of Serpine2-deficient (SE2(-/-)) mice, beginning at or before the time of lung maturity, which resulted in lesions that resembled bronchus-associated lymphoid tissue (BALT). The initiation of lymphocyte accumulation in the lungs of SE2(-/-) mice involved the excessive expression of chemokines, cytokines, and adhesion molecules that are essential for BALT induction, organization, and maintenance. BALT-like lesion formation in the lungs of SE2(-/-) mice was also associated with a significant increase in the activation of thrombin, a recognized target of SE2, and excess stimulation of NF-κB, a major regulator of chemokine expression and inflammation. Finally, systemic delivery of thrombin rapidly stimulated lung chemokine expression in vivo These data uncover a novel mechanism whereby loss of serine protease inhibition leads to lung lymphocyte accumulation.-Solleti, S. K., Srisuma, S., Bhattacharya, S., Rangel-Moreno, J., Bijli, K. M., Randall, T. D., Rahman, A., Mariani, T. J. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. © FASEB.

Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.

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Wang, Yaping; Zhao, Zhen; Zhu, Zhiyong; Li, Pingying; Li, Xiaolin; Xue, Xiaohong; Duo, Jie; Ma, Yingcai

2018-02-17

The effects of acute hypoxia at high altitude on the telomere length of the cells in the heart and lung tissues remain unclear. This study aimed to investigate the change in telomere length of rat heart and lung tissue cells in response to acute exposure to severe hypoxia and its role in hypoxia-induced damage to heart and lung tissues. Forty male Wistar rats (6-week old) were randomized into control group (n = 10) and hypoxia group (n = 30). Rats in control group were kept at an altitude of 1500 m, while rats in hypoxia group were exposed to simulated hypoxia with an altitude of 5000 m in a low-pressure oxygen chamber for 1, 3, and 7 days (n = 10). The left ventricular and right middle lobe tissues of each rat were collected for measurement of telomere length and reactive oxygen species (ROS) content, and the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor1α (HIF-1α), and hypoxia-inducible factor1α (HIF-2α). Increased exposure to hypoxia damaged rat heart and lung tissue cells and increased ROS production and telomere length. The mRNA and protein levels of TERT and HIF-1α were significantly higher in rats exposed to hypoxia and increased with prolonged exposure; mRNA and protein levels of HIF-2α increased only in rats exposed to hypoxia for 7 days. TERT was positively correlated with telomere length and the levels of HIF-1α but not HIF-2α. Acute exposure to severe hypoxia causes damage to heart and lung tissues due to the production of ROS but promotes telomere length and adaptive response by upregulating TERT and HIF-1α, which protect heart and lung tissue cells from fatal damage.

Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats

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YU, HONG-REN; LI, SUNG-CHOU; TSENG, WAN-NING; TAIN, YOU-LIN; CHEN, CHIH-CHENG; SHEEN, JIUNN-MING; TIAO, MAO-MENG; KUO, HO-CHANG; HUANG, CHAO-CHENG; HSIEH, KAI-SHENG; HUANG, LI-TUNG

2016-01-01

Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required. PMID:26997989

Resolvin D1 prevents smoking-induced emphysema and promotes lung tissue regeneration.

Science.gov (United States)

Kim, Kang-Hyun; Park, Tai Sun; Kim, You-Sun; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

2016-01-01

Emphysema is an irreversible disease that is characterized by destruction of lung tissue as a result of inflammation caused by smoking. Resolvin D1 (RvD1), derived from docosahexaenoic acid, is a novel lipid that resolves inflammation. The present study tested whether RvD1 prevents smoking-induced emphysema and promotes lung tissue regeneration. C57BL/6 mice, 8 weeks of age, were randomly divided into four groups: control, RvD1 only, smoking only, and smoking with RvD1 administration. Four different protocols were used to induce emphysema and administer RvD1: mice were exposed to smoking for 4 weeks with poly(I:C) or to smoking only for 24 weeks, and RvD1 was injected within the smoking exposure period to prevent regeneration or after completion of smoking exposure to assess regeneration. The mean linear intercept and inflammation scores were measured in the lung tissue, and inflammatory cells and cytokines were measured in the bronchoalveolar lavage fluid. Measurements of mean linear intercept showed that RvD1 significantly attenuated smoking-induced lung destruction in all emphysema models. RvD1 also reduced smoking-induced inflammatory cell infiltration, which causes the structural derangements observed in emphysema. In the 4-week prevention model, RvD1 reduced the smoking-induced increase in eosinophils and interleukin-6 in the bronchoalveolar lavage fluid. In the 24-week prevention model, RvD1 also reduced the increased neutrophils and total cell counts induced by smoking. RvD1 attenuated smoking-induced emphysema in vivo by reducing inflammation and promoting tissue regeneration. This result suggests that RvD1 may be useful in the prevention and treatment of emphysema.

Varied effects of thoracic irradiation on peripheral lymphocyte subsets in lung cancer patients

International Nuclear Information System (INIS)

Nakayama, Yasuhiro; Makino, Shigeki; Fukuda, Yasuki; Min, Kyong-Yob; Ikemoto, Toshiyuki; Shimizu, Akira; Ohsawa, Nakaaki

1995-01-01

To investigate the influence of thoracic irradiation on immunological competence in patients with lung cancer, we examined the changes in peripheral blood lymphocyte subsets in 15 patients before and after radiation therapy by two-color flow cytometry techniques. After radiation therapy, the percentage and the absolute number of CD4+CD45RA+ cells (naive T cells) and CD56+and/orCD16+ cells (NK cells) decreased. The percentage of CD4+ human leukocyte antigen-DR(HLA-DR)+ cells (activated CD4T cells) and CD8+HLA-DR+ cells (activated CD8T cells) increased, although the absolute number did not change significantly. Naive T cells may be more selectively damaged than memory T cells by thoracic irradiation, through their recirculation behavior. The reduction of natural killer (NK) cells is disadvantageous for anti-tumor immunity. The percentage of HLA-DR positive T lymphocytes was significantly increased, and thus the possibility of HLA-DR enhancement by irradiation cannot be excluded. Therefore, thoracic irradiation has numerous varied effects on the immunological system of lung cancer patients. (author)

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

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Kami, Kenjiro; Fujimori, Tamaki; Sato, Hajime; Sato, Mutsuko; Yamamoto, Hiroyuki; Ohashi, Yoshiaki; Sugiyama, Naoyuki; Ishihama, Yasushi; Onozuka, Hiroko; Ochiai, Atsushi; Esumi, Hiroyasu; Soga, Tomoyoshi; Tomita, Masaru

2013-04-01

Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics.

Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice

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Chai, Y; Calaf, G M; Zhou, H; Ghandhi, S A; Elliston, C D; Wen, G; Nohmi, T; Amundson, S A; Hei, T K

2013-01-01

Background: Although radiation-induced bystander effects have been confirmed using a variety of endpoints, the mechanism(s) underlying these effects are not well understood, especially for in vivo study. Methods: A 1-cm2 area (1 cm × 1 cm) in the lower abdominal region of gpt delta transgenic mice was irradiated with 5 Gy of 300 keV X-rays, and changes in out-of-field lung and liver were observed. Results: Compared with sham-treated controls, the Spi− mutation frequency increased 2.4-fold in non-targeted lung tissues at 24 h after partial body irradiation (PBIR). Consistent with dramatic Cyclooxygenase 2 (COX-2) induction in the non-targeted bronchial epithelial cells, increasing levels of prostaglandin, together with 8-hydroxydeoxyguanosine, in the out-of-field lung tissues were observed after PBIR. In addition, DNA double-strand breaks and apoptosis were induced in bystander lung tissues after PBIR. Conclusion: The PBIR induces DNA damage and mutagenesis in non-targeted lung tissues, especially in bronchial epithelial cells, and COX-2 has an essential role in bystander mutagenesis. PMID:23321513

Critical transition in tissue homeostasis accompanies murine lung senescence.

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Carla L Calvi

Full Text Available BACKGROUND: Respiratory dysfunction is a major contributor to morbidity and mortality in aged populations. The susceptibility to pulmonary insults is attributed to "low pulmonary reserve", ostensibly reflecting a combination of age-related musculoskeletal, immunologic and intrinsic pulmonary dysfunction. METHODS/PRINCIPAL FINDINGS: Using a murine model of the aging lung, senescent DBA/2 mice, we correlated a longitudinal survey of airspace size and injury measures with a transcriptome from the aging lung at 2, 4, 8, 12, 16 and 20 months of age. Morphometric analysis demonstrated a nonlinear pattern of airspace caliber enlargement with a critical transition occurring between 8 and 12 months of age marked by an initial increase in oxidative stress, cell death and elastase activation which is soon followed by inflammatory cell infiltration, immune complex deposition and the onset of airspace enlargement. The temporally correlative transcriptome showed exuberant induction of immunoglobulin genes coincident with airspace enlargement. Immunohistochemistry, ELISA analysis and flow cytometry demonstrated increased immunoglobulin deposition in the lung associated with a contemporaneous increase in activated B-cells expressing high levels of TLR4 (toll receptor 4 and CD86 and macrophages during midlife. These midlife changes culminate in progressive airspace enlargement during late life stages. CONCLUSION/SIGNIFICANCE: Our findings establish that a tissue-specific aging program is evident during a presenescent interval which involves early oxidative stress, cell death and elastase activation, followed by B lymphocyte and macrophage expansion/activation. This sequence heralds the progression to overt airspace enlargement in the aged lung. These signature events, during middle age, indicate that early stages of the aging immune system may have important correlates in the maintenance of tissue morphology. We further show that time-course analyses of aging

Proteoglycan changes in the extracellular matrix of lung tissue from patients with pulmonary emphysema

NARCIS (Netherlands)

van Straaten, JFM; Coers, W; Noordhoek, JA; Flipsen, JTM; Kauffman, HF; Timens, W; Postma, DS

To characterize the changes in the extracellular matrix in smoking-related pulmonary emphysema, we undertook immunohistochemical studies in lung tissues from controls (n = 7), from patients with mild (n = 11) and severe (n = 8) emphysema, and from patients with lung fibrosis (n = 6). We studied

Tissue Clearance of {sup 131}I and Total Peripheral Resistance in Myocardial Infarction and Hypertension, and During Angiotensin Infusion

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Bauer, F. K.; Bors, K. J.; Long, T. E.; Lestina, J. [University of Southern California School of Medicine, Los Angeles, CA (United States)

1971-02-15

Tissue clearance of {sup 131}I from the thigh, cardiac output and peripheral resistance was determined in 25 patients: 13 normotensive with recent myocardial infarction but not in congestive heart failure, 7 with hypertension and 5 normotensive control subjects. The effect of the synthesized pressor agent Angiotensin II on the same three measurements was also studied. The present investigation continues a previous one of ours, where a tracer dose of {sup 131}I was injected into the thigh of patients with recent myocardial infarction without signs of heart failure, and its clearance was found to be longer than that of normal subjects. This was thought to be due to increased peripheral resistance or to reduced perfusion of the capillary bed secondary to lowered cardiac output, With the 25 subjects, injection into the thigh of tracer amounts of radioactive iodine was done by Hypospray, a method with distinct advantages over needle injection. After measuring tissue clearance of the tracer, cardiac output was determined by a method which records the transit of the injected radioactive bolus through the heart. The Angiotensin was administered by intravenous infusion to four of the normotensive and one of the hypertensive patients. Calculations of cardiac output, total peripheral resistance, mean blood pressure and blood volume were made by means of standard formulae. Results of the study confirmed expectations. Those patients with myocardial infarction who had delayed tissue clearance of {sup 131}I also had reduced cardiac output. The patients with hypertension had normal tissue clearance of {sup 131}I and normal cardiac output in the presence of increased peripheral resistance. Equivalent hypertension and increased peripheral resistance induced in normotensive subjects by Angiotensin resulted in lowered cardiac output and delayed tissue clearance of {sup 131}I. An increased sensitivity to Angiotensin was noted in hypertensive patients. The tissue clearance of {sup 131}I

Adenoviral vector-mediated expression of a foreign gene in peripheral nerve tissue bridges implanted in the injured peripheral and central nervous system

NARCIS (Netherlands)

Blits, B; Dijkhuizen, Paul A; Carlstedt, Thomas P; Poldervaart, H A; Schiemanck, S; Boer, G J; Verhaagen, J

1999-01-01

Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This is due to a different microenvironment at the site of the lesion as well as a particular intrinsic program of axonal regrowth. Although transplantation of peripheral nerve tissue bridges is perhaps the

TH-C-12A-02: Comparison of Two RapidArc Delivery Strategies in Stereotactic Body Radiotherapy of Stage I and II Peripheral Lung Tumors with Unflattened Beams

International Nuclear Information System (INIS)

Huang, B; Lu, J; Chen, J; Chen, C; Lin, P; Kuang, Y

2014-01-01

Purpose: The full arcs strategy used in SBRT with RapidArc and unflattened (FFF) beams in large and heterogeneous peripheral non-smallcell lung cancer (NSCLC) appears to be suboptimal as it increases the disadvantageous dose to the contralateral lung, which potentially increases the toxicity to surrounding tissues. In this study, we investigated, for the first time, the dose delivery strategies using partial arcs (PA) and the fully rotational arcs with avoidance sectors (FAAS) for SBRT with FFF beams in peripheral NSCLC patients. Methods: Eighteen patients with NSCLC (stage I and II) were selected for this study. Nine patients with a GTV <= 10cc were designated as the small tumor group. The remaining nine patients with a GTV between 10 cc and 44 cc were assigned to the large tumor group. The treatment plans were generated in eighteen patients using PA and FAAS, respectively, and delivered with a Varian TrueBeam Linac. Dosimetry of the target and organs at risk (OAR), total MU, out-of-field dose, and delivery time were analyzed. Delta4 and Portal dosimetry were employed to evaluate the delivery accuracy. Results: or the small tumor group, the FAAS plans significantly achieved a better conformity index, the lower total MU and out-of-field dose, a shorter treatment time, and the reduced doses to cord, heart, and lung (p < 0.05). But the target doses were slightly higher than that delivered by PA plans. For the large tumor group, the PA plans significantly attained a better conformity index and a shorter treatment time (p < 0.05). Furthermore, all plans achieved a high pass rate, with all the gamma indices greater than 97% at the Γ 3mm, 3% threshold. Conclusion: This study suggests that FAAS strategy is more beneficial for small tumor patients undergoing lung SBRT with FFF beams. However, for large tumor patients, PA strategy is recommended. NIH/NIGMS grant U54 GM104944, Lincy Endowed Assistant Professorship

Polydeoxyribonucleotide Improves Peripheral Tissue Oxygenation and Accelerates Angiogenesis in Diabetic Foot Ulcers

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Seoyoung Kim

2017-11-01

Full Text Available Background Polydeoxyribonucleotide (PDRN is known to have anti-inflammatory and angiogenic effects and to accelerate wound healing. The aim of this study was to investigate whether PDRN could improve peripheral tissue oxygenation and angiogenesis in diabetic foot ulcers. Methods This was a prospective randomized controlled clinical trial. Twenty patients with a non-healing diabetic foot ulcer were randomly distributed into a control group (n=10 and a PDRN group (n=10. Initial surgical debridement and secondary surgical procedures such as a split-thickness skin graft, primary closure, or local flap were performed. Between the initial surgical debridement and secondary surgical procedures, 0.9% normal saline (3 mL or PDRN was injected for 2 weeks by the intramuscular (1 ampule, 3 mL, 5.625 mg, 5 days per week and perilesional routes (1 ampule, 3 mL, 5.625 mg, 2 days per week. Transcutaneous oxygen tension (TcPO2 was evaluated using the Periflux System 5000 with TcPO2/CO2 unit 5040 before the injections and on days 1, 3, 7, 14, and 28 after the start of the injections. A pathologic review (hematoxylin and eosin stain of the debrided specimens was conducted by a pathologist, and vessel density (average number of vessels per visual field was calculated. Results Compared with the control group, the PDRN-treated group showed improvements in peripheral tissue oxygenation on day 7 (P<0.01, day 14 (P<0.001, and day 28 (P<0.001. The pathologic review of the specimens from the PDRN group showed increased angiogenesis and improved inflammation compared with the control group. No statistically significant difference was found between the control group and the PDRN group in terms of vessel density (P=0.094. Complete healing was achieved in every patient. Conclusions In this study, PDRN improved peripheral tissue oxygenation. Moreover, PDRN is thought to be effective in improving inflammation and angiogenesis in diabetic foot ulcers.

Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration

NARCIS (Netherlands)

Meek, MF; den Dunnen, WFA; Schakenraad, JM; Robinson, PH

The aim of this study was to (1) evaluate the effect of several preparation techniques of denatured muscle tissue to obtain an open three-dimensional structure, and (2) test if this scaffold is suitable for peripheral nerve regeneration. Four samples (A-D) of muscle tissue specimens were evaluated

Use of radioimmunodetection of carcinoembryonic antigen (CEA) and ferritin in diagnosis of lung cancer

International Nuclear Information System (INIS)

Zamyatin, S.S.; Zakharychev, V.D.

1989-01-01

To study the diagnostic value of radioimmunoassay (RIA) of carcinoembryonic antigen (CEA) and ferritin the level of this markers under lung cancer depending on the tumor localization and the process stage is determined. It is shown that determination of CEA and ferritin level in a number of patients with the peripheral lung cancer allows on the confirm the diagnosis. In case of the central cancer an increase of CEA level testifies to the tumor germination into the adjacent organs and lung tissue and allows one to determine the stage and operability of the disease. 10 refs.; 3 tabs

Response of rat lung tissue to short-term hyperoxia: a proteomic approach.

Science.gov (United States)

Spelten, Oliver; Wetsch, Wolfgang A; Wrettos, Georg; Kalenka, Armin; Hinkelbein, Jochen

2013-11-01

An inspiratory oxygen fraction of 1.0 is often required to avoid hypoxia both in many pre- and in-hospital situations. On the other hand, hyperoxia may lead to deleterious consequences (cell growth inhibition, inflammation, and apoptosis) for numerous tissues including the lung. Whereas clinical effects of hyperoxic lung injury are well known, its impact on the expression of lung proteins has not yet been evaluated sufficiently. The aim of this study was to analyze time-dependent alterations of protein expression in rat lung tissue after short-term normobaric hyperoxia (NH). After approval of the local ethics committee for animal research, N = 36 Wistar rats were randomized into six different groups: three groups with NH with exposure to 100 % oxygen for 3 h and three groups with normobaric normoxia (NN) with exposure to room air (21 % oxygen). After the end of the experiments, lungs were removed immediately (NH0 and NN0), after 3 days (NH3 and NN3) and after 7 days (NH7 and NN7). Lung lysates were analyzed by two-dimensional gel electrophoresis (2D-GE) followed by peptide mass fingerprinting using mass spectrometry. Statistical analysis was performed with Delta 2D (DECODON GmbH, Greifswald, Germany; ANOVA, Bonferroni correction, p pO2 was significantly higher in NH-groups compared to NN-groups (581 ± 28 vs. 98 ± 12 mmHg; p < 0.01), all other physiological parameters did not differ. Expression of 14 proteins were significantly altered: two proteins were up-regulated and 12 proteins were down-regulated. Even though NH was comparatively short termed, significant alterations in lung protein expression could be demonstrated up to 7 days after hyperoxia. The identified proteins indicate an association with cell growth inhibition, regulation of apoptosis, and approval of structural cell integrity.

Peripheral soft tissue hemangioma: MRI and histo-pathologic correlation (a report of 32 cases)

International Nuclear Information System (INIS)

Hu Xiaojun; Zhou Haiwei; Shao Haijun; Li Chunsheng

2007-01-01

Objective: To analyze the MRI findings of hemangiomas derived from soft tissue. Methods: MRI was performed on 32 cases with mass in the peripheral soft tissue. All cases were confirmed to be hemangioma histo-pathologically. Results: The masses were classified as four patterns on this series, namely: cavernous hemangiomas, 15 cases (46.9%), displayed as a spindle-shaped or irregular mass; Racemose, 9 cases (28%), had an honeycombed or racemose appearance; Capillary, 5 cases (15.6%), with an elongated mass-like configuration; Mixed, 3 case(9.4%), showed as an amouphus mass. The masses usually had equal or higher signal intensity as compared to muscle on T 1 WI and markedly high signal intensity on T 2 WI. Focal inhomogeneities of the lesions in pathological study represent areas of fibrosia, fat, thrombosis, smooth muscle or calcificatin. Conclusion: MRI is an useful tool not only to identifying the locatoion of the mass but also could specify the peripheral soft tisure hemangioma. (authors)

Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

Science.gov (United States)

Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

2014-01-01

The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

5-Aza-2'-deoxycytidine protects against emphysema in mice via suppressing p16Ink4a expression in lung tissue

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He ZH

2017-10-01

Full Text Available Zhi-Hui He,1 Yan Chen,2 Ping Chen,2 Sheng-Dong He,2 Hui-Hui Zeng,2 Ji-Ru Ye,2 Da Liu,2 Jun Cao3 1Intensive Care Unit, 2Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha, 3Department of Respiratory Medicine, Hunan Provincial People’s Hospital, Changsha, China Background: There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs contribute to neovascularization and play an important role in the development of COPD. The gene for p16Ink4a is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16Ink4a in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE, and further to search for a potential candidate agent protecting against emphysema induced by CSE. Materials and methods: An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16Ink4a protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively. Results: CSE induced emphysema with increased p16Ink4a expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16Ink4a in EPCs and lung tissue induced by CSE. Conclusion: 5-Aza-CdR partly protected against emphysema in mice via suppressing p16Ink4a expression in EPCs and lung tissue. Keywords: 5-Aza-2'-deoxycytidine, cigarette smoke, emphysema, endothelial progenitor cells, p16Ink4a

[Expression of high mobility group box-1 in the lung tissue and serum of patients with pulmonary tuberculosis].

Science.gov (United States)

Yang, Xiao-min; Yang, Hua

2013-07-01

To explore the expression of high mobility group box-1 (HMGB1) in the lung tissue and serum of patients with pulmonary tuberculosis and to explore its relationship with tumor necrosis factor (TNF)-α and interleukin(IL)-1β. Sixty samples of lung tissues were obtained from patients with pulmonary tuberculosis who had underwent pneumonectomy in Department of Chest Surgery, First Affiliated Hospital of Zunyi Medical College from June 2010 to December 2011. At the same period, 40 normal lung samples were also obtained from patients with pulmonary contusion and lung cancer by surgical resections as the control group. The mRNA expressions of HMGB1 was detected by reverse transcription-polymerase chain reaction (RT-PCR), and the protein level of HMGB1 was measured by immunohistochemical staining of tissue microarrays in lung tissue. Blood samples were taken from 89 patients with active pulmonary tuberculosis (pulmonary tuberculosis group), including hematogenous disseminated pulmonary tuberculosis (type II) in 35 cases and secondary pulmonary tuberculosis (type III) in 54 cases, and 50 healthy volunteers (control group). Furthermore, the 54 patients with secondary pulmonary tuberculosis were divided into different subgroups according to cavity formation and the lung fields involved: patients without lung cavity (35 cases) vs those with lung cavity (19 cases), patients with involvement of pulmonary tuberculosis (69 ± 29) was significantly higher than that in normal lung tissue (22 ± 12) (t = 2.389, P pulmonary tuberculosis (786 ± 86) was significantly higher than that in normal lung tissue (202 ± 60) (t = 3.872, P pulmonary tuberculosis group were (5.0 ± 3.2) µg/L, (118 ± 77) ng/L and (33 ± 20) ng/L, respectively, which were significantly higher than those in the control group [(1.7 ± 1.0) µg/L, (40 ± 11) ng/L and (18 ± 12) ng/L, respectively], the respective t values being -0.928, 4.268 and 11.064, all P pulmonary tuberculosis, the serum concentration of HMGB

Histochemical, light and electron microscopic study of polonium-210 induced peripheral tumours in hamster lungs -evidence implicating the Clara Cell as the cell of origin

International Nuclear Information System (INIS)

Kennedy, A.R.; McGandy, R.B.; Little, J.B.

1977-01-01

Peripheral lung tumors induced in Syrian golden hamsters by intratracheally administered polonium-210 ( 210 Po) are similar to the peripheral lung tumours induced in many species by a variety of carcinogens. In addition, they show many of the histopathological features observed in human bronchiolar-alveolar carcinomas. Serial sacrifice studies of hamsters exposed to multiple instillations of 210 Po have been carried our to identify the cell of origin of these tumors. By means of thin, plastic (glycol methacrylate) sections, electron microscopy, and histochemistry, it is concluded that the bronchiolar Clara cell is the probable cell of origin, and that this view is generally compatible with many of the reported cytological characteristics of the human tumor. (author)

Pulmonary lymphangioleiomyomatosis: Analysis of disease manifestation by region-based quantification of lung parenchyma

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Theilig, D., E-mail: dorothea.theilig@charite.de [Charité, Universitätsmedizin Berlin, Department of Radiology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Doellinger, F. [Charité, Universitätsmedizin Berlin, Department of Radiology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany); Kuhnigk, J.M. [Fraunhofer MEVIS, Universitaetsallee 29, 28359 Bremen (Germany); Temmesfeld-Wollbrueck, B.; Huebner, R.H. [Charité, Department of Pneumology, Augustenburger Platz 1, 13353 Berlin (Germany); Schreiter, N.; Poellinger, A. [Charité, Universitätsmedizin Berlin, Department of Radiology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin (Germany)

2015-04-15

Highlights: •The distribution of cystic lesions in LAM was evaluated with quantitative CT. •There were more cystic lesions in the central lung compared to peripheral areas. •Cystic changes were more frequent in apical two thirds compared to lower third. •Results might help to obviate the need for biopsy in more cases. -- Abstract: Purpose: Lymphangioleiomyomatosis (LAM) is characterized by proliferation of smooth muscle tissue that causes bronchial obstruction and secondary cystic destruction of lung parenchyma. The aim of this study was to evaluate the typical distribution of cystic defects in LAM with quantitative volumetric chest computed tomography (CT). Materials and methods: CT examinations of 20 patients with confirmed LAM were evaluated with region-based quantification of lung parenchyma. Additionally, 10 consecutive patients were identified who had recently undergone CT imaging of the lung at our institution, in which no pathologies of the lung were found, to serve as a control group. Each lung was divided into three regions (upper, middle and lower thirds) with identical number of slices. In addition, we defined a “peel” and “core” of the lung comprising the 2 cm subpleural space and the remaining inner lung area. Computerized detection of lung volume and relative emphysema was performed with the PULMO 3D software (v3.42, Fraunhofer MEVIS, Bremen, Germany). This software package enables the quantification of emphysematous lung parenchyma by calculating the pixel index, which is defined as the ratio of lung voxels with a density <−950 HU to the total number of voxels in the lung. Results: Cystic changes accounted for 0.1–39.1% of the total lung volume in patients with LAM. Disease manifestation in the central lung was significantly higher than in peripheral areas (peel median: 15.1%, core median: 20.5%; p = 0.001). Lower thirds of lung parenchyma showed significantly less cystic changes than upper and middle lung areas combined (lower

Influence of industrial dust of uranium ore on rats' lung tissue

International Nuclear Information System (INIS)

Jumasheva, R.T.

2010-01-01

Under the conditions of radiotoxic influence of uranium ore dust (UOD), the respiratory organs are the main system specifically responsible for adaptation to this factor. At the same time, there are not sufficient studies regarding the morphological aspects of structural lung distortions due to inhalational influence by UOD. To identify the nature of morphological changes in the animals' lung tissue at the cellular and subcellular levels under the influence of industrial dust of uranium ore in a dose of 50 MPC. Experimental studies were conducted on 80 white rats (tom) with a body mass of 120-180 g. The experimental animals were subjected to chronic inhalation of UOD in a dose of 50 MPC (107.75 mg/m 3 ). The animals that were kept in similar chambers but that were not exposed to UOD served as control animals. Material from the animals for research was withdrawn in 3, 7, 30 and 60 days after the beginning of the experiment. The animals were withdrawn from the experiment by decapitation after a brief ether anesthesia. The lung tissue was subjected to conventional histological processing. Sections were stained with haematoxylin and eosin according to van Gieson's method. For electronic microscopic examination the lung tissue slices were fixed and embedded by conventional methods. Obtained blocks were used to prepare ultrathin sections. An impact of UOD in a dose of 50 MPC was accompanied by the development of acute focal serous inflammation in the wall of the small bronchi and lung parenchyma in the early stages of the experiment (3-7 days), pneumonic foci of fibrosis, and the development of marked sclerotic changes in the peribronchial lymphoid tissue by the 30-th day. By the 60-th day, an increase of sclerotic changes in the bronchial wall accompanied by inhibition of the reaction on the part of interstitial macrophages and bronchus associated lymphoid tissue were reported. These indicate the intense course of the compensatory processes. Conducted electron

An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries.

Science.gov (United States)

Patel, Nitesh P; Lyon, Kristopher A; Huang, Jason H

2018-05-01

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

Science.gov (United States)

Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

2018-06-01

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy

The relationship among human papilloma virus infection, survivin, and p53 gene in lung squamous carcinoma tissue

International Nuclear Information System (INIS)

Yue-Hua Wang; De-jie Chen; Tie-Nan Yi

2010-01-01

To study the relationship between the infection of human papillomavirus (HPV) type 16, type 18, the expression of survivin, and the mutation of p53 gene in lung squamous carcinoma tissue for the research of pathogenesis of lung carcinoma.This study was carried out at the Laboratory of Molecular Biology, Xiangfan Central Hospital of Hubei Province, China from September 2008 to May 2010. Forty-five specimens of lung squamous carcinoma tissue confirmed by histopathology were the excisional specimens taken by the Thoracic Surgery of Xiangfan Central Hospital. Normal tissue, closely adjacent to the fresh carcinoma specimens, was used as the control group for p53 gene mutation analysis. Sixteen surgical excisional specimens of benign lung disease were used as a control group of non-carcinomatous diseases. Human papillomavirus DNA were detected by polymerase chain reaction (PCR), and we used the PCR-single-strand conformation polymorphism-ethidium bromide (PCR-SSCP-EB) method to detect the mutations of the p53 gene. The expression of the survivin gene was detected by immunohistochemistry methods. Approximately 68.9% of 45 lung squamous carcinoma tissue had p53 gene mutations. The mutation rate of exon 5-8 p53 were 15.6%, 17.8%, 15.6% and 20%. Approximately 42.2% of lung squamous cell carcinoma samples were shown to be positive for HPV DNA expression and 62.2% were positive for survivin expression. There was an inverse correlation between the presence of HPV infections and mutations of p53 gene; and the mutations of p53 gene and expression of survivin had a positive relationship. Mutation of p53 gene and HPV infection may facilitate each other in the generation of lung squamous cell carcinoma. Abnormal expression of the survivin gene may take part in the onset and progression of lung squamous cell carcinoma (Author).

Absorbed dose calculation of the energy deposition close to bone, lung and soft tissue interfaces in molecular radiotherapy

International Nuclear Information System (INIS)

Fernandez, M.; Lassman, M.

2015-01-01

Full text of publication follows. Aim: for voxel-based dosimetry in molecular radiotherapy (MRT) based on tabulated voxel S-values these values are usually obtained only for soft tissue. In order to study the changes in the dose deposition patterns at interfaces between different materials we have performed Monte Carlo simulations. Methods: the deposited energy patterns were obtained using the Monte-Carlo radiation code MCNPX v2.7 for Lu 177 (medium-energy) and Y 90 (high-energy). The following interfaces were studied: soft tissue-bone and soft tissue-lungs. For this purpose a volume of soft tissue homogeneously filled with Lu 177 or Y 90 was simulated at the interface to 3 different volumes containing no activity: soft tissue, lungs and bone. The emission was considered to be isotropic. The dimensions were chosen to ensure that the energy deposited by all generated particles was scored. The materials were defined as recommended by ICPR46; the decay schemes of Eckerman and Endo were used. With these data the absorbed dose patterns normalized to the maximum absorbed dose in the source region (soft tissue) were calculated. Results: the absorbed dose fractions in the boundary with soft tissue, bone and lungs are 50%, 47% and 57%, respectively, for Lu 177 and 50%, 47% and 51% for Y 90 . The distances to the interface at which the absorbed fractions are at 0.1% are 1.0, 0.6 and 3.0 mm for Lu 177 and 7.0, 4.0 and 24 mm for Y 90 , for soft tissue, bone and lungs respectively. Conclusions: in MRT, the changes in the absorbed doses at interfaces between soft tissue and bone/lungs need to be considered for isotopes emitting high energy particles. (authors)

Differential N-glycan patterns identified in lung adenocarcinoma by N-glycan profiling of formalin-fixed paraffin-embedded (FFPE) tissue sections.

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Wang, Xiaoning; Deng, Zaian; Huang, Chuncui; Zhu, Tong; Lou, Jiatao; Wang, Lin; Li, Yan

2018-02-10

N-glycan profiling is a powerful approach for analyzing the functional relationship between N-glycosylation and cancer. Current methods rely on either serum or fresh tissue samples; however, N-glycan patterns may differ between serum and tissue, as the proteins of serum originate from a variety of tissues. Furthermore, fresh tissue samples are difficult to ship and store. Here, we used a profiling method based on formalin-fixed paraffin-embedded (FFPE) tissue sections from lung adenocarcinoma patients. We found that our method was highly reproducible. We identified 58 N-glycan compositions from lung adenocarcinoma FFPE samples, 51 of which were further used for MS n -based structure prediction. We show that high mannose type N-glycans are upregulated, while sialylated N-glycans are downregulated in our FFPE lung adenocarcinoma samples, compared to the control samples. Our receiver operating characteristic (ROC) curve analysis shows that high mannose type and sialylated N-glycans are useful discriminators to distinguish between lung adenocarcinoma and control tissue. Together, our results indicate that expression levels of specific N-glycans correlate well with lung adenocarcinoma, and strongly suggest that our FFPE-based method will be useful for N-glycan profiling of cancer tissues. Glycosylation is one of the most important post-translational protein modifications, and is associated with several physiopathological processes, including carcinogenesis. In this study, we tested the feasibility of using formalin-fixed paraffin-embedded (FFPE) tissue sections to identify changes in N-glycan patterns and identified the differentially expressed N-glycans of lung adenocarcinoma. Our study shows that the FFPE-based N-glycan profiling method is useful for clinical diagnosis as well as identification of potential biomarkers, and our data expand current knowledge of differential N-glycan patterns of lung adenocarcinoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues

OpenAIRE

Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R; Romer, Micah; Tufik, Sergio; Pack, Allan I

2013-01-01

Background Many have assumed that the primary function of sleep is for the brain. We evaluated the molecular consequences of sleep and sleep deprivation outside the brain, in heart and lung. Using microarrays we compared gene expression in tissue from sleeping and sleep deprived mice euthanized at the same diurnal times. Results In each tissue, nearly two thousand genes demonstrated statistically significant differential expression as a function of sleep/wake behavioral state. To mitigate the...

Impact of 4D-(18)FDG-PET/CT imaging on target volume delineation in SBRT patients with central versus peripheral lung tumors. Multi-reader comparative study.

Science.gov (United States)

Chirindel, Alin; Adebahr, Sonja; Schuster, Daniel; Schimek-Jasch, Tanja; Schanne, Daniel H; Nemer, Ursula; Mix, Michael; Meyer, Philipp; Grosu, Anca-Ligia; Brunner, Thomas; Nestle, Ursula

2015-06-01

Evaluation of the effect of co-registered 4D-(18)FDG-PET/CT for SBRT target delineation in patients with central versus peripheral lung tumors. Analysis of internal target volume (ITV) delineation of central and peripheral lung lesions in 21 SBRT-patients. Manual delineation was performed by 4 observers in 2 contouring phases: on respiratory gated 4DCT with diagnostic 3DPET available aside (CT-ITV) and on co-registered 4DPET/CT (PET/CT-ITV). Comparative analysis of volumes and inter-reader agreement. 11 cases of peripheral and 10 central lesions were evaluated. In peripheral lesions, average CT-ITV was 6.2 cm(3) and PET/CT-ITV 8.6 cm(3), resembling a mean change in hypothetical radius of 2 mm. For both CT-ITVs and PET/CT-ITVs inter reader agreement was good and unchanged (0.733 and 0.716; p=0.58). All PET/CT-ITVs stayed within the PTVs derived from CT-ITVs. In central lesions, average CT-ITVs were 42.1 cm(3), PET/CT-ITVs 44.2 cm(3), without significant overall volume changes. Inter-reader agreement improved significantly (0.665 and 0.750; p1 ml in average for all observers. The addition of co-registered 4DPET data to 4DCT based target volume delineation for SBRT of centrally located lung tumors increases the inter-observer agreement and may help to avoid geographic misses. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Transgenic Mice Overexpressing Vitamin D Receptor (VDR) Show Anti-Inflammatory Effects in Lung Tissues.

Science.gov (United States)

Ishii, Masaki; Yamaguchi, Yasuhiro; Isumi, Kyoko; Ogawa, Sumito; Akishita, Masahiro

2017-12-01

Vitamin D insufficiency is increasingly recognized as a prevalent problem worldwide, especially in patients with a chronic lung disease. Chronic obstructive pulmonary disease (COPD) is a type of chronic inflammatory lung disease. Previous clinical studies have shown that COPD leads to low vitamin D levels, which further increase the severity of COPD. Vitamin D homeostasis represents one of the most important factors that potentially determine the severity of COPD. Nonetheless, the mechanisms underlying the anti-inflammatory effects of vitamin D receptor (VDR) in lung tissues are still unclear. To investigate the anti-inflammatory effects of VDR, we generated transgenic mice that show lung-specific VDR overexpression under the control of the surfactant protein C promoter (TG mice). The TG mice were used to study the expression patterns of proinflammatory cytokines using real-time polymerase chain reaction and immunohistochemistry. The TG mice had lower levels of T helper 1 (Th1)-related cytokines than wild-type (WT) mice did. No significant differences in the expression of Th2 cytokines were observed between TG and WT mice. This study is the first to achieve lung-specific overexpression of VDR in TG mice: an interesting animal model useful for studying the relation between airway cell inflammation and vitamin D signaling. VDR expression is an important factor that influences anti-inflammatory responses in lung tissues. Our results show the crucial role of VDR in anti-inflammatory effects in lungs; these data are potentially useful for the treatment or prevention of COPD.

[Molecular markers of Alzheimer disease early diagnostic: investigation perspectives of peripheral tissues.

Science.gov (United States)

Paltsev, M A; Zuev, V A; Kozhevnikova, E O; Linkova, N S; Kvetnaia, T V; Polyakova, V O; Kvetnoy, I M

2017-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of elderly and old age people. For intravital diagnosis of the expression of signaling molecules - AD markers, cerebrospinal fluid (CSF) and peripheral tissues are used: lymphocytes and blood platelets, buccal and olfactory epithelium, skin fibroblasts. There are several changes in the production of hyper phosphorylated form of τ-protein, BACE1 and peptide Аβ42 in CSF in case of AD, but CSF taking may have a number of side effects. Less traumatic taking of sampling tissues for the diagnosis of AD is in use of epithelium biopsy and blood portion. An increase in the expression of the hyper phosphorylated form of τ-protein is shown in blood lymphocytes of AD patients. An increase in the content of high molecular weight forms of phosphorylated t-protein and amyloid precursor protein-APP was also revealed in blood platelets of AD patients. Changes in the amount of 2 miRNA families - miR-132 family and miR-134 family were revealed in blood cells 1-5 years before the manifestation of clinical signs of AD. An increase in the concentration of bound calcium, synthesis of peptides Aβ40 and Aβ42, τ protein was observed in AD skin fibroblasts. In the olfactory and buccal epithelium an increase in the expression of hyper phosphorylated form of τ-protein and Aβ peptide was detected in patients with AD. Verification of AD markers in peripheral tissues for biopsy have the important significant for life diagnostics, prevention and and target AD treatment.

Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

Science.gov (United States)

Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

2015-05-01

Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 - 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery.

Decellularized Rat Lung Scaffolds Using Sodium Lauryl Ether Sulfate for Tissue Engineering.

Science.gov (United States)

Ma, Jinhui; Ju, Zhihai; Yu, Jie; Qiao, Yeru; Hou, Chenwei; Wang, Chen; Hei, Feilong

Perfusion decellularization with detergents is effective to maintain the architecture and proteins of extracellular matrix (ECM) for use in the field of lung tissue engineering (LTE). However, it is unclear which detergent is ideal to produce an acellular lung scaffold. In this study, we obtained two decellularized rat lung scaffolds using a novel detergent sodium lauryl ether sulfate (SLES) and a conventional detergent sodium dodecyl sulfate (SDS). Both decellularized lung scaffolds were assessed by histology, immunohistochemistry, scanning electron microscopy, DNA quantification, sulfated glycosaminoglycans (GAGs) quantification and western blot. Subsequently, the scaffolds were implanted subcutaneously in rats for 6 weeks and were evaluated via hematoxylin and eosin staining and Masson staining. Results indicated that SLES was effective to remove cells; moreover, lungs decellularized with SLES showed better preservation of sulfated GAGs, lung architecture, and ECM proteins than SDS. After 6 weeks, SLES scaffolds demonstrated a significantly greater potential for cell infiltration and blood vessel formation compared with SDS scaffolds. Taken together, we conclude that SLES is a promising detergent to produce an acellular scaffold using LTE for eventual transplantation.

Distribution of soya-saponin in brain and peripheral tissue after peritoneal injection

International Nuclear Information System (INIS)

Zhu Shigong; Wang Jianchun; Zhang Peiyin

1997-01-01

125 I-soya-saponin was prepared to study the distribution of soya-saponin in body of rat, as well as in different areas of brain when peritoneal injection. The results showed that the peak value of radioactive soya-saponin in all tissue appeared at 30 min after peritoneal injection. There were higher radioactivities in brain and suprarene comparing with other organs. The highest radioactivity was seen in hypothalamus among the every brain areas. It is a first report that soyasaponin can pass through the blood brain barrier when peripheral injection. The result also supported the opinion that soyasaponin might act on the hypothalamus and central regulation of cardiovascular system. Another finding was that soyasaponin also showed a higher affinity with adrenal gland, which indicated that the soyasaponin might possess of peripheral effect for regulation of cardiovascular system as well

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

DEFF Research Database (Denmark)

Skjøt-Arkil, Helene; Clausen, Rikke E; Nguyen, Quoc Hai Trieu

2012-01-01

Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part...... are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases....

Expression of Nitric Oxide Synthase Isoenzyme in Lung Tissue of Smokers with and without Chronic Obstructive Pulmonary Disease

Directory of Open Access Journals (Sweden)

Wen-Ting Jiang

2015-01-01

Full Text Available Background: It has been demonstrated that only 10%-20% cigarette smokers finally suffer chronic obstructive pulmonary disease (COPD. The underlying mechanism of development remains uncertain so far. Nitric oxide (NO has been found to be closely associated with the pathogenesis of COPD, the alteration of NO synthase (NOS expression need to be revealed. The study aimed to investigate the alterations of NOS isoforms expressions between smokers with and without COPD, which might be helpful for identifying the susceptibility of smokers developing into COPD. Methods: Peripheral lung tissues were obtained from 10 nonsmoker control subjects, 15 non-COPD smokers, and 15 smokers with COPD. Neuronal NOS (nNOS, inducible NOS (iNOS, and endothelial NOS (eNOS mRNA and protein levels were measured in each sample by using real-time polymerase chain reaction and Western blotting. Results: INOS mRNA was significantly increased in patients with COPD compared with nonsmokers and smokers with normal lung function (P < 0.001, P = 0.001, respectively. iNOS protein was also higher in COPD patients than nonsmokers and smokers with normal lung function (P < 0.01 and P = 0.01, respectively. However, expressions of nNOS and eNOS did not differ among nonsmokers, smokers with and without COPD. Furthermore, there was a negative correlation between iNOS protein level and lung function parameters forced expiratory volume in 1 s (FEV 1 (% predicted (r = −0.549, P = 0.001 and FEV 1 /forced vital capacity (%, r = −0.535, P = 0.001. Conclusions: The expression of iNOS significantly increased in smokers with COPD compared with that in nonsmokers or smokers without COPD. The results suggest that iNOS might be involved in the pathogenesis of COPD, and may be a potential marker to identify the smokers who have more liability to suffer COPD.

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery.

Science.gov (United States)

Rottmann, Joerg; Keall, Paul; Berbeco, Ross

2013-09-01

To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient. 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps. Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

Activation of SF1 Neurons in the Ventromedial Hypothalamus by DREADD Technology Increases Insulin Sensitivity in Peripheral Tissues.

Science.gov (United States)

Coutinho, Eulalia A; Okamoto, Shiki; Ishikawa, Ayako Wendy; Yokota, Shigefumi; Wada, Nobuhiro; Hirabayashi, Takahiro; Saito, Kumiko; Sato, Tatsuya; Takagi, Kazuyo; Wang, Chen-Chi; Kobayashi, Kenta; Ogawa, Yoshihiro; Shioda, Seiji; Yoshimura, Yumiko; Minokoshi, Yasuhiko

2017-09-01

The ventromedial hypothalamus (VMH) regulates glucose and energy metabolism in mammals. Optogenetic stimulation of VMH neurons that express steroidogenic factor 1 (SF1) induces hyperglycemia. However, leptin acting via the VMH stimulates whole-body glucose utilization and insulin sensitivity in some peripheral tissues, and this effect of leptin appears to be mediated by SF1 neurons. We examined the effects of activation of SF1 neurons with DREADD (designer receptors exclusively activated by designer drugs) technology. Activation of SF1 neurons by an intraperitoneal injection of clozapine- N -oxide (CNO), a specific hM3Dq ligand, reduced food intake and increased energy expenditure in mice expressing hM3Dq in SF1 neurons. It also increased whole-body glucose utilization and glucose uptake in red-type skeletal muscle, heart, and interscapular brown adipose tissue, as well as glucose production and glycogen phosphorylase a activity in the liver, thereby maintaining blood glucose levels. During hyperinsulinemic-euglycemic clamp, such activation of SF1 neurons increased insulin-induced glucose uptake in the same peripheral tissues and tended to enhance insulin-induced suppression of glucose production by suppressing gluconeogenic gene expression and glycogen phosphorylase a activity in the liver. DREADD technology is thus an important tool for studies of the role of the brain in the regulation of insulin sensitivity in peripheral tissues. © 2017 by the American Diabetes Association.

Silver Nanoparticles in the Lung: Toxic Effects and Focal Accumulation of Silver in Remote Organs

Directory of Open Access Journals (Sweden)

Martin Wiemann

2017-12-01

Full Text Available The distribution of silver (Ag into remote organs secondary to the application of Ag nanoparticles (Ag-NP to the lung is still incompletely understood and was investigated in the rat with imaging methods. Dose-finding experiments were carried out with 50 nm- or 200 nm-sized polyvinyl pyrrolidine (PVP-coated Ag-NP using alveolar macrophages in vitro and female rats, which received Ag-NP via intratracheal instillation. In the main study, we administered 37.5–300 µg per rat lung of the more toxic Ag50-PVP and assessed the broncho-alveolar lavage fluid (BALF for inflammatory cells, total protein and fibronectin after three and 21 days. In parallel, lung tissue was analysed for DNA double-strand breaks and altered cell proliferation. While 75–150 µg Ag50-PVP per rat lung caused a reversible inflammation, 300 µg led to DNA damage, accelerated cell proliferation and progressively increasing numbers of neutrophilic granulocytes. Ag accumulation was significant in homogenates of liver and other peripheral organs upon lung dose of ≥75 µg. Quantitative laser-ablation inductively-coupled plasma mass spectrometry (LA-ICP-MS combined with enhanced dark field microscopy and autometallography revealed focal accumulations of Ag and/or Ag-NP in sections of peripheral organs: mediastinal lymph nodes contained Ag-NP especially in peripheral macrophages and Ag in argyrophilic fibres. In the kidney, Ag had accumulated within proximal tubuli, while renal filter structures contained no Ag. Discrete localizations were also observed in immune cells of liver and spleen. Overall, the study shows that concentrations of Ag-NP, which elicit a transient inflammation in the rat lung, lead to focal accumulations of Ag in peripheral organs, and this might pose a risk to particular cell populations in remote sites.

Investigating the bioavailability of graphene quantum dots in lung tissues via Fourier transform infrared spectroscopy.

Science.gov (United States)

Tabish, Tanveer A; Lin, Liangxu; Ali, Muhammad; Jabeen, Farhat; Ali, Muhammad; Iqbal, Rehana; Horsell, David W; Winyard, Paul G; Zhang, Shaowei

2018-06-06

Biomolecular fractions affect the fate and behaviour of quantum dots (QDs) in living systems but how the interactions between biomolecules and QDs affect the bioavailability of QDs is a major knowledge gap in risk assessment analysis. The transport of QDs after release into a living organism is a complex process. The majority accumulate in the lungs where they can directly affect the inhalation process and lung architecture. Here, we investigate the bioavailability of graphene quantum dots (GQDs) to the lungs of rats by measuring the alterations in macromolecular fractions via Fourier transform infrared spectroscopy (FTIR). GQDs were intravenously injected into the rats in a dose-dependent manner (low (5 mg kg -1 ) and high (15 mg kg -1 ) doses of GQDs per body weight of rat) for 7 days. The lung tissues were isolated, processed and haematoxylin-eosin stained for histological analysis to identify cell death. Key biochemical differences were identified by spectral signatures: pronounced changes in cholesterol were found in two cases of low and high doses; a change in phosphorylation profile of substrate proteins in the tissues was observed in low dose at 24 h. This is the first time biomolecules have been measured in biological tissue using FTIR to investigate the biocompatibility of foreign material. We found that highly accurate toxicological changes can be investigated with FTIR measurements of tissue sections. As a result, FTIR could form the basis of a non-invasive pre-diagnostic tool for predicting the toxicity of GQDs.

Metallic artifact mitigation and organ-constrained tissue assignment for Monte Carlo calculations of permanent implant lung brachytherapy

Energy Technology Data Exchange (ETDEWEB)

Sutherland, J. G. H.; Miksys, N.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca [Carleton Laboratory for Radiotherapy Physics, Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Furutani, K. M. [Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905 (United States)

2014-01-15

Purpose: To investigate methods of generating accurate patient-specific computational phantoms for the Monte Carlo calculation of lung brachytherapy patient dose distributions. Methods: Four metallic artifact mitigation methods are applied to six lung brachytherapy patient computed tomography (CT) images: simple threshold replacement (STR) identifies high CT values in the vicinity of the seeds and replaces them with estimated true values; fan beam virtual sinogram replaces artifact-affected values in a virtual sinogram and performs a filtered back-projection to generate a corrected image; 3D median filter replaces voxel values that differ from the median value in a region of interest surrounding the voxel and then applies a second filter to reduce noise; and a combination of fan beam virtual sinogram and STR. Computational phantoms are generated from artifact-corrected and uncorrected images using several tissue assignment schemes: both lung-contour constrained and unconstrained global schemes are considered. Voxel mass densities are assigned based on voxel CT number or using the nominal tissue mass densities. Dose distributions are calculated using the EGSnrc user-code BrachyDose for{sup 125}I, {sup 103}Pd, and {sup 131}Cs seeds and are compared directly as well as through dose volume histograms and dose metrics for target volumes surrounding surgical sutures. Results: Metallic artifact mitigation techniques vary in ability to reduce artifacts while preserving tissue detail. Notably, images corrected with the fan beam virtual sinogram have reduced artifacts but residual artifacts near sources remain requiring additional use of STR; the 3D median filter removes artifacts but simultaneously removes detail in lung and bone. Doses vary considerably between computational phantoms with the largest differences arising from artifact-affected voxels assigned to bone in the vicinity of the seeds. Consequently, when metallic artifact reduction and constrained tissue

Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

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Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

2018-01-03

Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

Percentages of NKT cells in the tissues of patients with non-small cell lung cancer who underwent surgical treatment.

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Pyszniak, Maria; Rybojad, Paweł; Pogoda, Katarzyna; Jabłonka, Andrzej; Bojarska-Junak, Agnieszka; Tabarkiewicz, Jacek

2014-03-01

Natural killer T (NKT) cells are involved in the antitumor response by direct cytotoxicity and indirectly through activation of effector cells. Recent studies have shown a relationship between the number and function of NKT cells and clinical outcomes. NKT cells seem to represent a promising tool for immunotherapy of cancer. The aim of the study was to evaluate the distribution of NKT cells in peripheral blood, lymph nodes and tumor tissue of non-small cell lung cancer (NSCLC) patients, as well as development of the most efficient set of cytokines stimulating differentiation of NKT cells. We evaluated the percentage of iNKT+CD3+ cells in the tissues collected from patients with NSCLC. For the generation of NKT cells, we cultured cells isolated from the blood of 20 healthy donors and from the tissues of 4 NSCLC patients. Cells were stimulated with α-GalCer in combinations with cytokines. We noted significant differences in the percentages of NKT cells in the patients' tissues. The highest percentage of these cells was observed in the tumor tissue and the lowest in the lymph nodes. In vitro, in healthy donors all α-GalCer-cytokine combinations were effective in stimulation of NKT cells' proliferation. NKT cells' proliferation was the most efficiently stimulated by α-GalCer+IL-2+IL-7 and α-GalCer+IL-2+IFN-γ. Our results suggest that in the course of NSCLC, NKT cells migrate to the primary tumor and accumulate therein. All tested combinations of α-GalCer and cytokines were capable of generation of NKT cells in vitro.

Over-expression of thymosin β4 in granulomatous lung tissue with active pulmonary tuberculosis.

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Kang, Yun-Jeong; Jo, Jin-Ok; Ock, Mee Sun; Yoo, Young-Bin; Chun, Bong-Kwon; Oak, Chul-Ho; Cha, Hee-Jae

2014-05-01

Recent studies have shown that thymosin β4 (Tβ4) stimulates angiogenesis by inducing vascular endothelial growth factor (VEGF) expression and stabilizing hypoxia inducible factor-1α (HIF-1α) protein. Pulmonary tuberculosis (TB), a type of granulomatous disease, is accompanied by intense angiogenesis and VEGF levels have been reported to be elevated in serum or tissue inflamed by pulmonary tuberculosis. We investigated the expression of Tβ4 in granulomatous lung tissues at various stages of active pulmonary tuberculosis, and we also examined the expression patterns of VEGF and HIF-1α to compare their Tβ4 expression patterns in patients' tissues and in the tissue microarray of TB patients. Tβ4 was highly expressed in both granulomas and surrounding lymphocytes in nascent granulomatous lung tissue, but was expressed only surrounding tissues of necrotic or caseous necrotic regions. The expression pattern of HIF-1α was similar to that of Tβ4. VEGF was expressed in both granulomas and blood vessels surrounding granulomas. The expression pattern of VEGF co-localized with CD31 (platelet endothelial cell adhesion molecule, PECAM-1), a blood endothelial cell marker, and partially co-localized with Tβ4. However, the expression of Tβ4 did not co-localize with alveolar macrophages. Stained alveolar macrophages were present surrounding regions of granuloma highly expressing Tβ4. We also analyzed mRNA expression in the sputum of 10 normal and 19 pulmonary TB patients. Expression of Tβ4 was significantly higher in patients with pulmonary tuberculosis than in normal controls. These data suggest that Tβ4 is highly expressed in granulomatous lung tissue with active pulmonary TB and is associated with HIF-1α- and VEGF-mediated inflammation and angiogenesis. Furthermore, the expression of Tβ4 in the sputum of pulmonary tuberculosis patients can be used as a potential marker for diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Endogenous peripheral hydrogen sulfide is propyretic: its permissive role in brown adipose tissue thermogenesis in rats.

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Soriano, Renato N; Braga, Sara P; Breder, Jéssica S C; Batalhao, Marcelo E; Oliveira-Pelegrin, Gabriela R; Ferreira, Luiz Fernando R; Rocha, Maria José A; Carnio, Evelin C; Branco, Luiz G S

2018-03-01

What is the central question of this study? In fever, the most striking response in the acute phase reaction of systemic inflammation, plasma H 2 S concentration increases. However, the role of endogenous peripheral H 2 S in fever is unknown. What is the main finding and its importance? Endogenous peripheral H 2 S is permissive for increased brown adipose tissue thermogenesis to maintain thermal homeostasis in cold environments as well as to mount fever. This finding expands the physiological role of the gaseous modulator as a key regulator of thermal control in health (thermal homeostasis) and disease (fever in systemic inflammation). In recent years, hydrogen sulfide (H 2 S) has been reported as a gaseous modulator acting in several tissues in health and disease. In animal models of systemic inflammation, the plasma H 2 S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but we found no reports of the peripheral action of H 2 S on this thermoregulatory response. We aimed at investigating whether endogenous systemic H 2 S modulates LPS-induced fever. A temperature datalogger capsule was inserted in the abdominal cavity of male Wistar rats (220-270 g) to record body core temperature. These animals received an i.p. injection of a systemic H 2 S inhibitor (propargylglycine; 50 or 75 mg kg -1 ), immediately followed by an i.p. injection of LPS (50 or 2500 μg kg -1 ), and were exposed to different ambient temperatures (16, 22 or 27°C). At 22°C, but not at 27°C, propargylglycine at 75 mg kg -1 significantly attenuated (P endogenous peripheral H 2 S on brown adipose tissue (BAT) thermogenesis. Evidence on the modulatory role of peripheral H 2 S in BAT thermogenesis was strengthened when we discarded (i) the possible influence of the gas on febrigenic signalling (when measuring plasma cytokines), and (ii) its interaction with the nitric

HU deviation in lung and bone tissues: Characterization and a corrective strategy.

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Ai, Hua A; Meier, Joseph G; Wendt, Richard E

2018-05-01

In the era of precision medicine, quantitative applications of x-ray Computed Tomography (CT) are on the rise. These require accurate measurement of the CT number, also known as the Hounsfield Unit. In this study, we evaluated the effect of patient attenuation-induced beam hardening of the x-ray spectrum on the accuracy of the HU values and a strategy to correct for the resulting deviations in the measured HU values. A CIRS electron density phantom was scanned on a Siemens Biograph mCT Flow CT scanner and a GE Discovery 710 CT scanner using standard techniques that are employed in the clinic to assess the HU deviation caused by beam hardening in different tissue types. In addition, an anthropomorphic ATOM adult male upper torso phantom was scanned on the GE Discovery 710 scanner. Various amounts of Superflab bolus material were wrapped around the phantoms to simulate different patient sizes. The mean HU values that were measured in the phantoms were evaluated as a function of the water-equivalent area (A w ), a parameter that is described in the report of AAPM Task Group 220. A strategy by which to correct the HU values was developed and tested. The variation in the HU values in the anthropomorphic ATOM phantom under different simulated body sizes, both before and after correction, were compared, with a focus on the lung and bone tissues. Significant HU deviations that depended on the simulated patient size were observed. A positive correlation between HU and A w was observed for tissue types that have an HU of less than zero, while a negative correlation was observed for tissue types with HU values that are greater than zero. The magnitude of the difference increases as the underlying attenuation property deviates further away from that of water. In the electron density phantom study, the maximum observed HU differences between the measured and reference values in the cortical bone and lung materials were 426 and 94 HU, respectively. In the anthropomorphic phantom

Detection of EGFR and COX-2 Expression by Immunohistochemical Method on a Tissue Microarray Section in Lung Cancer and Biological Significance

Directory of Open Access Journals (Sweden)

Xinyun WANG

2010-02-01

Full Text Available Background and objective Epidermal growth factor receptor (EGFR and cyclooxygenase-2 (COX-2, which can regulate growth, invasion and metastasis of tumor through relevant signaling pathway, have been detected in a variety of solid tumors. The aim of this study is to investigate the biological significance of EGFR and COX-2 expression in lung cancer and the relationship between them. Methods The expression of EGFR and COX-2 was detected in 89 primary lung cancer tissues, 12 premaliganant lesions, 12 lymph node metastases, and 10 normal lung tissues as the control by immunohistochemical method on a tissue microarray section. Results EGFR protein was detectable in 59.6%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively; COX-2 protein was detectable in 52.8%, 41.7%, and 66.7% of primary lung cancer tissues, premalignant lesions and lymph node metastases, respectively, which were significantly higher than those of the control (P 0.05. COX-2 expression was related to gross type (P < 0.05. A highly positive correlation was observed between EGFR and COX-2 expression (P < 0.01. Conclusion Overexpression of EGFR and COX-2 may play an important role in the tumorgenesis, progression and malignancy of lung cancer. Detection of EGFR and COX-2 expression might be helpful to diagnosis and prognosis of lung cancer.

Radiological characteristics, histological features and clinical outcomes of lung cancer patients with coexistent idiopathic pulmonary fibrosis.

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Khan, K A; Kennedy, M P; Moore, E; Crush, L; Prendeville, S; Maher, M M; Burke, L; Henry, M T

2015-02-01

Despite advances in diagnosis and management, the outcomes for both lung cancer and idiopathic pulmonary fibrosis (IPF) are still unfavourable. The pathophysiology and outcomes for patients with concomitant lung cancer and IPF remains unclear. A retrospective analysis was performed of all patients presenting with concomitant IPF and lung cancer to our centre over a 3-year period. Patients with connective tissue disease, asbestos exposure, sarcoidosis, previous thoracic radiation, radiological evidence of fibrosis but no histological confirmation of lung cancer, or the use of medications known to cause pulmonary fibrosis were excluded. We describe clinical, radiological and pathological characteristics of this group. We also report the response to standardized lung cancer therapy in this cohort. Of 637 lung cancer patients, 34 were identified with concomitant IPF (5.3 %) and all were smokers. 85 % had non-small cell lung cancer, 41 % were squamous cell cancers. The majority of tumours were located in the lower lobes, peripheral and present in an area of honeycombing. Despite the fact that approximately 2/3rds of the patients had localised or locally advanced lung cancer, the outcome of therapy for lung cancer was extremely poor regardless of tumour stage or severity of IPF. At our centre, 1/20 patients with lung cancer have concomitant IPF. The majority of these tumours are small in size, peripheral in location and squamous cell carcinoma; in an area of honey combing. The outcome for concomitant lung cancer and IPF regardless of stage or therapy is poor.

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

International Nuclear Information System (INIS)

Rottmann, Joerg; Berbeco, Ross; Keall, Paul

2013-01-01

Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time

Real-time soft tissue motion estimation for lung tumors during radiotherapy delivery

Energy Technology Data Exchange (ETDEWEB)

Rottmann, Joerg; Berbeco, Ross [Brigham and Women' s Hospital, Dana Farber-Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Keall, Paul [Radiation Physics Laboratory, Sydney Medical School, University of Sydney, Sydney NSW 2006 (Australia)

2013-09-15

Purpose: To provide real-time lung tumor motion estimation during radiotherapy treatment delivery without the need for implanted fiducial markers or additional imaging dose to the patient.Methods: 2D radiographs from the therapy beam's-eye-view (BEV) perspective are captured at a frame rate of 12.8 Hz with a frame grabber allowing direct RAM access to the image buffer. An in-house developed real-time soft tissue localization algorithm is utilized to calculate soft tissue displacement from these images in real-time. The system is tested with a Varian TX linear accelerator and an AS-1000 amorphous silicon electronic portal imaging device operating at a resolution of 512 × 384 pixels. The accuracy of the motion estimation is verified with a dynamic motion phantom. Clinical accuracy was tested on lung SBRT images acquired at 2 fps.Results: Real-time lung tumor motion estimation from BEV images without fiducial markers is successfully demonstrated. For the phantom study, a mean tracking error <1.0 mm [root mean square (rms) error of 0.3 mm] was observed. The tracking rms accuracy on BEV images from a lung SBRT patient (≈20 mm tumor motion range) is 1.0 mm.Conclusions: The authors demonstrate for the first time real-time markerless lung tumor motion estimation from BEV images alone. The described system can operate at a frame rate of 12.8 Hz and does not require prior knowledge to establish traceable landmarks for tracking on the fly. The authors show that the geometric accuracy is similar to (or better than) previously published markerless algorithms not operating in real-time.

Monoclonal antibody to a subset of human monocytes found only in the peripheral blood and inflammatory tissues

Energy Technology Data Exchange (ETDEWEB)

Zwadlo, G.; Schlegel, R.; Sorg, C.

1986-07-15

A monoclonal antibody is described that was generated by immunizing mice with cultured human blood monocytes. The antibody (27E10) belongs to the IgG1 subclass and detects a surface antigen at M/sub r/ 17,000 that is found on 20% of peripheral blood monocytes. The antigen is increasingly expressed upon culture of monocytes, reaching a maximum between days 2 and 3. Stimulation of monocytes with interferon-..gamma.. (IFN-..gamma..), 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and lipopolysaccharide (LPS) Ylalanine (fMLP) increased the 27E10 antigen density. The amount of 27E10-positive cells is not or is only weakly affected. The antigen is absent from platelets, lymphotyces, and all tested human cell lines, yet it cross-reacts with 15% of freshly isolated granulocytes. By using the indirect immunoperoxidase technique, the antibody is found to be negative on cryostat sections of normal human tissue (skin, lung, and colon) and positive on only a few monocyte-like cells in liver and on part of the cells of the splenic red pulp. In inflammatory tissue, however, the antibody is positive on monocytes/macrophages and sometimes on endothelial cells and epidermal cells, depending on the stage and type of inflammation, e.g., BCG ranulomas are negative, whereas psoriasis vulgaris, atopic dermatitis, erythrodermia, pressure urticaria, and periodontitis contain positively staining cells. In contact eczemas at different times after elicitation (6 hr, 24 hr, and 72 hr), the 27E10 antigen is seen first after 24 hr on a few infiltrating monocytes/macrophages, which increase in numbers after 72 hr.

[The effects of postconditioning with propofol on Toll-like receptor 4 expression in the lung tissue of rat with acute lung injury].

Science.gov (United States)

Li, Guo-Fu; Tong, Xin; Luan, Ting; Zang, Bin

2012-10-01

To investigate the effect of postconditioning with propofol on Toll-like receptor 4 (TLR4) expression in the lung tissue in lipopolysaccharide (LPS)-induced acute lung injury (ALI) rats. Thirty Sprague-Dawley (SD) rats were randomly assigned to control group, ALI group, and propofol postcondition group (each n=10). The model of ALI was reproduced by intravenous injection of LPS (8 mg/kg for 30 minutes) into the rats, equivalent normal saline was injected into the rats of control group. The rats were postconditioned with propofol injected intravenously by 20 mg/kg bolus dose and then continuously by 40 mg×kg(-1)×h(-1) with a constant speed for 1 hour. The rats were sacrificed 6 hours after drug injection. Lung wet/dry weight (W/D) ratio and lung permeability index (LPI) was taken. Tumor necrosis factor-α (TNF-α) level in bronchoalveolar lavage fluid (BALF) was detected using enzyme linked immunosorbent assay (ELISA) method and TLR4 mRNA expression in lung tissue was assessed by reverse transcription-polymerase chain reaction (RT-PCR). The lung W/D ratio, LPI, TLR4 mRNA and TNF-α in BALF were all increased in ALI group compared with control group [lung W/D ratio: 5.30±0.28 vs. 4.21±0.14, LPI (×10(-3)): 8.7±2.2 vs. 3.3±2.0, TLR4 mRNA: 2.451±0.028 vs. 0.998±0.021, TNF-α: 643.46±62.31 ng/L vs. 120.43±12.65 ng/L, all Pwaterfall-like inflammatory reaction.

An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

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Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

2015-01-01

Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons. PMID:26200940

Isolation of Blastomyces dermatitidis yeast from lung tissue during murine infection for in vivo transcriptional profiling.

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Marty, Amber J; Wüthrich, Marcel; Carmen, John C; Sullivan, Thomas D; Klein, Bruce S; Cuomo, Christina A; Gauthier, Gregory M

2013-07-01

Blastomyces dermatitidis belongs to a group of thermally dimorphic fungi that grow as sporulating mold in the soil and convert to pathogenic yeast in the lung following inhalation of spores. Knowledge about the molecular events important for fungal adaptation and survival in the host remains limited. The development of high-throughput analytic tools such as RNA sequencing (RNA-Seq) has potential to provide novel insight on fungal pathogenesis especially if applied in vivo during infection. However, in vivo transcriptional profiling is hindered by the low abundance of fungal cells relative to mammalian tissue and difficulty in isolating fungal cells from the tissues they infect. For the purpose of obtaining B. dermatitidis RNA for in vivo transcriptional analysis by RNA-Seq, we developed a simple technique for isolating yeast from murine lung tissue. Using a two-step approach of filtration and centrifugation following lysis of murine lung cells, 91% of yeast cells causing infection were isolated from lung tissue. B. dermatitidis recovered from the lung yielded high-quality RNA with minimal murine contamination and was suitable for RNA-Seq. Approximately 87% of the sequencing reads obtained from the recovered yeast aligned with the B. dermatitidis genome. This was similar to 93% alignment for yeast grown in vitro. The use of near-freezing temperature along with short ex vivo time minimized transcriptional changes that would have otherwise occurred with higher temperature or longer processing time. In conclusion, we have developed a technique that recovers the majority of yeast causing pulmonary infection and yields high-quality fungal RNA with minimal contamination by mammalian RNA. Copyright © 2013 Elsevier Inc. All rights reserved.

Abnormalities in lung volumes and airflow in children with newly diagnosed connective tissue disease.

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Peradzyńska, Joanna; Krenke, Katarzyna; Szylling, Anna; Kołodziejczyk, Beata; Gazda, Agnieszka; Rutkowska-Sak, Lidia; Kulus, Marek

2016-01-01

Connective tissue diseases (CTDs) of childhood are rare inflammatory disorders, involving various organs and tissues including respiratory system. Pulmonary involvement in patients with CTDs is uncommon but may cause functional impairment. Data on prevalence and type of lung function abnormalities in children with CTDs are scarce. Thus, the aim of this study was to asses pulmonary functional status in children with newly diagnosed CTD and follow the results after two years of the disease course. There were 98 children (mean age: 13 ± 3; 76 girls), treated in Department of Pediatric Rheumatology, Institute of Rheumatology, Warsaw and 80 aged-matched, healthy controls (mean age 12.7 ± 2.4; 50 girls) included into the study. Study procedures included medical history, physical examination, chest radiograph and PFT (spirometry and whole body-plethysmography). Then, the assessment of PFT was performed after 24 months. FEV₁, FEV₁/FVC and MEF50 were significantly lower in CTD as compared to control group, there was no difference in FVC and TLC. The proportion of patients with abnormal lung function was significantly higher in the study group, 41 (42%) vs 9 (11%). 24-months observation didn't reveal progression in lung function impairment. Lung function impairment is relatively common in children with CTDs. Although restrictive ventilatory pattern is considered typical feature of lung involvement in CTDs, airflow limitation could also be an initial abnormality.

Photoperiodic regulation of PER1 and PER2 protein expression in rat peripheral tissues

Czech Academy of Sciences Publication Activity Database

Bendová, Zdeňka; Sumová, Alena

2006-01-01

Roč. 55, č. 6 (2006), s. 623-632 ISSN 0862-8408 R&D Projects: GA ČR(CZ) GP309/02/D093; GA MŠk(CZ) LC554 Grant - others:EUCLOCK(XE) 018741 Institutional research plan: CEZ:AV0Z50110509 Keywords : circadian rhythms * peripheral tissue * PER proteins Subject RIV: FH - Neurology Impact factor: 2.093, year: 2006

Explicit formula of finite difference method to estimate human peripheral tissue temperatures during exposure to severe cold stress.

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Khanday, M A; Hussain, Fida

2015-02-01

During cold exposure, peripheral tissues undergo vasoconstriction to minimize heat loss to preserve the maintenance of a normal core temperature. However, vasoconstricted tissues exposed to cold temperatures are susceptible to freezing and frostbite-related tissue damage. Therefore, it is imperative to establish a mathematical model for the estimation of tissue necrosis due to cold stress. To this end, an explicit formula of finite difference method has been used to obtain the solution of Pennes' bio-heat equation with appropriate boundary conditions to estimate the temperature profiles of dermal and subdermal layers when exposed to severe cold temperatures. The discrete values of nodal temperature were calculated at the interfaces of skin and subcutaneous tissues with respect to the atmospheric temperatures of 25 °C, 20 °C, 15 °C, 5 °C, -5 °C and -10 °C. The results obtained were used to identify the scenarios under which various degrees of frostbite occur on the surface of skin as well as the dermal and subdermal areas. The explicit formula of finite difference method proposed in this model provides more accurate predictions as compared to other numerical methods. This model of predicting tissue temperatures provides researchers with a more accurate prediction of peripheral tissue temperature and, hence, the susceptibility to frostbite during severe cold exposure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Peripheral laser iridoplasty opens angle in plateau iris by thinning the cross-sectional tissues

Directory of Open Access Journals (Sweden)

Liu J

2013-09-01

Full Text Available Ji Liu,1,2 Tania Lamba,1 David A Belyea1 1Department of Ophthalmology, The George Washington University, Washington DC, USA; 2Yale Eye Center, Yale University, New Haven, CT, USA Abstract: Plateau iris syndrome has been described as persistent angle narrowing or occlusion with intraocular pressure elevation after peripheral iridotomy due to the abnormal plateau iris configuration. Argon laser peripheral iridoplasty (ALPI is an effective adjunct procedure to treat plateau iris syndrome. Classic theory suggests that the laser causes the contraction of the far peripheral iris stroma, "pulls" the iris away from the angle, and relieves the iris-angle apposition. We report a case of plateau iris syndrome that was successfully treated with ALPI. Spectral domain optical coherence tomography confirmed the angle was open at areas with laser treatment but remained appositionally closed at untreated areas. Further analysis suggested significant cross-sectional thinning of the iris at laser-treated areas in comparison with untreated areas. The findings indicate that APLI opens the angle, not only by contracting the iris stroma, but also by thinning the iris tissue at the crowded angle. This is consistent with the ALPI technique to aim at the iris as far peripheral as possible. This case also suggests that spectral domain optical coherence tomography is a useful adjunct imaging tool to gonioscopy in assessing the angle condition. Keywords: plateau iris, optic coherence tomography, argon laser peripheral iridoplasty, angle-closure glaucoma

Characterisation of lung tumour under dosage for interpretation of clinical trial data

International Nuclear Information System (INIS)

Taylor, M.L.; Dunn, L.; Franich, R.D.; Kron, T.; Height, F.

2010-01-01

Full text: It is well known that the periphery of lung tumours is under-dosed in radiotherapy as a result of electronic disequilibrium at the interface of lung and tumour tissue. Clinical trials often employ dose calculation algorithms which poorly approximate the dose to peripheral regions of tumour volumes. The aim of this study was to develop a set of systematic under-dosage estimates corresponding to various clinical parameters. High resolution Monte Carlo radiation transport calculations were undertaken for a systematic set of generic lung tumours irradiated with an external photon beam. Varied parameters include beam energy, field size, tumour size and distance to chest wall. Calculations were undertaken using both EGSnrc and GEAI T4. A 'Dose Reduction Factor' is defined which describes the dose to the peripheral 'shell' 01 the tumour, as relevant for multiple-field and arc therapy. For a 6 MV beam, under-dosage is typically between 2 and 5% for the different arrangements investigated, and for a 15 MV beam it is between 5 and 8% (relative to the central dose). Good agreement between EGSnrc and GEANT4 was demonstrated. Comparisons with pencil beam convolution calculations indicate that the treatment planning system does not identify this under-dosage. A systematic set of data has been obtained that characterises the extent of peripheral under-dosage in lung tumours for the retrospective evaluation of clinical trial data. The data presented i: also informative for clinics using less sophisticated planning algorithms, particularly when dose is being prescribed to covering isodoses. (author)

Human adipose tissue mesenchymal stromal cells and their extracellular vesicles act differentially on lung mechanics and inflammation in experimental allergic asthma.

Science.gov (United States)

de Castro, Ligia Lins; Xisto, Debora Gonçalves; Kitoko, Jamil Zola; Cruz, Fernanda Ferreira; Olsen, Priscilla Christina; Redondo, Patricia Albuquerque Garcia; Ferreira, Tatiana Paula Teixeira; Weiss, Daniel Jay; Martins, Marco Aurélio; Morales, Marcelo Marcos; Rocco, Patricia Rieken Macedo

2017-06-24

Asthma is a chronic inflammatory disease that can be difficult to treat due to its complex pathophysiology. Most current drugs focus on controlling the inflammatory process, but are unable to revert the changes of tissue remodeling. Human mesenchymal stromal cells (MSCs) are effective at reducing inflammation and tissue remodeling; nevertheless, no study has evaluated the therapeutic effects of extracellular vesicles (EVs) obtained from human adipose tissue-derived MSCs (AD-MSC) on established airway remodeling in experimental allergic asthma. C57BL/6 female mice were sensitized and challenged with ovalbumin (OVA). Control (CTRL) animals received saline solution using the same protocol. One day after the last challenge, each group received saline, 10 5 human AD-MSCs, or EVs (released by 10 5  AD-MSCs). Seven days after treatment, animals were anesthetized for lung function assessment and subsequently euthanized. Bronchoalveolar lavage fluid (BALF), lungs, thymus, and mediastinal lymph nodes were harvested for analysis of inflammation. Collagen fiber content of airways and lung parenchyma were also evaluated. In OVA animals, AD-MSCs and EVs acted differently on static lung elastance and on BALF regulatory T cells, CD3 + CD4 + T cells, and pro-inflammatory mediators (interleukin [IL]-4, IL-5, IL-13, and eotaxin), but similarly reduced eosinophils in lung tissue, collagen fiber content in airways and lung parenchyma, levels of transforming growth factor-β in lung tissue, and CD3 + CD4 + T cell counts in the thymus. No significant changes were observed in total cell count or percentage of CD3 + CD4 + T cells in the mediastinal lymph nodes. In this immunocompetent mouse model of allergic asthma, human AD-MSCs and EVs effectively reduced eosinophil counts in lung tissue and BALF and modulated airway remodeling, but their effects on T cells differed in lung and thymus. EVs may hold promise for asthma; however, further studies are required to elucidate the different

Development of a multivariate model to predict the likelihood of carcinoma in patients with indeterminate peripheral lung nodules after a nondiagnostic bronchoscopic evaluation.

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Voss, Jesse S; Iqbal, Seher; Jenkins, Sarah M; Henry, Michael R; Clayton, Amy C; Jett, James R; Kipp, Benjamin R; Halling, Kevin C; Maldonado, Fabien

2014-01-01

Studies have shown that fluorescence in situ hybridization (FISH) testing increases lung cancer detection on cytology specimens in peripheral nodules. The goal of this study was to determine whether a predictive model using clinical features and routine cytology with FISH results could predict lung malignancy after a nondiagnostic bronchoscopic evaluation. Patients with an indeterminate peripheral lung nodule that had a nondiagnostic bronchoscopic evaluation were included in this study (N = 220). FISH was performed on residual bronchial brushing cytology specimens diagnosed as negative (n = 195), atypical (n = 16), or suspicious (n = 9). FISH results included hypertetrasomy (n = 30) and negative (n = 190). Primary study end points included lung cancer status along with time to diagnosis of lung cancer or date of last clinical follow-up. Hazard ratios (HRs) were calculated using Cox proportional hazards regression model analyses, and P values < .05 were considered statistically significant. The mean age of the 220 patients was 66.7 years (range, 35-91), and most (58%) were men. Most patients (79%) were current or former smokers with a mean pack year history of 43.2 years (median, 40; range, 1-200). After multivariate analysis, hypertetrasomy FISH (HR = 2.96, P < .001), pack years (HR = 1.03 per pack year up to 50, P = .001), age (HR = 1.04 per year, P = .02), atypical or suspicious cytology (HR = 2.02, P = .04), and nodule spiculation (HR = 2.36, P = .003) were independent predictors of malignancy over time and were used to create a prediction model (C-statistic = 0.78). These results suggest that this multivariate model including test results and clinical features may be useful following a nondiagnostic bronchoscopic examination. © 2013.

The cryoablation of lung tissue using liquid nitrogen in gel and in the ex vivo pig lung.

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Nomori, Hiroaki; Yamazaki, Ikuo; Kondo, Toshiya; Kanno, Masaya

2017-02-01

To examine the efficiency of cryoablation using liquid nitrogen in lung tissue, we measured the size and temperature distribution of the frozen area (iceball) in gel and in the ex vivo pig lungs. Cryoprobes with diameters of 2.4 and 3.4 mm (2.4D and 3.4D, respectively) were used. Three temperature sensors were positioned at the surface of the cryoprobe and at distances of 0.5 and 1.5 cm from the cryoprobe. The ex vivo pig lungs were perfused with 37 °C saline and inflated using ventilator to simulate in vivo lung conditions. In gel, the 2.4D and 3.4D probes made iceballs of 3.9 ± 0.1 and 4.8 ± 0.3 cm in diameter, respectively, and the temperature at 1.5 cm from those probes reached -32 ± 8 and -53 ± 5 °C, respectively. In the pig lung, the 2.4D and 3.4D probes made iceballs of 5.2 ± 0.1 and 5.5 ± 0.4 cm in diameter, respectively, and the temperature at 1.5 cm from these probes reached -49 ± 5 and -58 ± 3 °C, respectively. Liquid nitrogen cryoablation using both 2.4D and 3.4D probes made iceballs that were of sufficient size, and effective temperatures were reached in both gel and the ex vivo pig lung.

Cell structure and proliferative activity of organ cultures of normal embryonic lung tissue of mice resistant (C57BL) and predisposed (A) to lung tumors

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Kolesnichenko, T.S.; Gor'kova, T.G.

1985-01-01

Local factors such as proliferative activity and the numerical ratio between epithelial and mesenchymal cells, and also the character of interaction between the tissue components in ontogeny may play an important role in the realization of sensitivity of mice of a particular line to the development of lung tumors. These characteristics of lung tissue in mice of lines A and C57BL are investigated under normal conditions and during induced carcinogenesis. Results are given of a comparative study of the relative numbers of epithelial and mesenchymal cells in organ cultures of embryonic lungs. 3 H-thymidine was added to the cultures on the 14th day of the experiment in a concentration of 1 microCi/m1 medium. An autoradiographic study of the cultures was performed

Lung Cancer Signature Biomarkers: tissue specific semantic similarity based clustering of Digital Differential Display (DDD data

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Srivastava Mousami

2012-11-01

Full Text Available Abstract Background The tissue-specific Unigene Sets derived from more than one million expressed sequence tags (ESTs in the NCBI, GenBank database offers a platform for identifying significantly and differentially expressed tissue-specific genes by in-silico methods. Digital differential display (DDD rapidly creates transcription profiles based on EST comparisons and numerically calculates, as a fraction of the pool of ESTs, the relative sequence abundance of known and novel genes. However, the process of identifying the most likely tissue for a specific disease in which to search for candidate genes from the pool of differentially expressed genes remains difficult. Therefore, we have used ‘Gene Ontology semantic similarity score’ to measure the GO similarity between gene products of lung tissue-specific candidate genes from control (normal and disease (cancer sets. This semantic similarity score matrix based on hierarchical clustering represents in the form of a dendrogram. The dendrogram cluster stability was assessed by multiple bootstrapping. Multiple bootstrapping also computes a p-value for each cluster and corrects the bias of the bootstrap probability. Results Subsequent hierarchical clustering by the multiple bootstrapping method (α = 0.95 identified seven clusters. The comparative, as well as subtractive, approach revealed a set of 38 biomarkers comprising four distinct lung cancer signature biomarker clusters (panel 1–4. Further gene enrichment analysis of the four panels revealed that each panel represents a set of lung cancer linked metastasis diagnostic biomarkers (panel 1, chemotherapy/drug resistance biomarkers (panel 2, hypoxia regulated biomarkers (panel 3 and lung extra cellular matrix biomarkers (panel 4. Conclusions Expression analysis reveals that hypoxia induced lung cancer related biomarkers (panel 3, HIF and its modulating proteins (TGM2, CSNK1A1, CTNNA1, NAMPT/Visfatin, TNFRSF1A, ETS1, SRC-1, FN1, APLP2, DMBT1

Monocyte Chemoattractant Protein-1 in the choroid plexus: a potential link between vascular pro-inflammatory mediators and the CNS during peripheral tissue inflammation

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Mitchell, K.; Yang, H.-Y. T.; Berk, J. D.; Tran, J. H.; Iadarola, M. J.

2009-01-01

During peripheral tissue inflammation, inflammatory processes in the CNS can be initiated by blood-borne pro-inflammatory mediators. The choroid plexus, the site of CSF production, is a highly specialized interface between the vascular system and CNS, and thus, this structure may be an important element in communication between the vascular compartment and the CNS during peripheral tissue inflammation. We investigated the potential participation of the choroid plexus in this process during peripheral tissue inflammation by examining expression of the SCYA2 gene which codes for monocyte chemoattractant protein-1 (MCP-1). MCP-1 protein was previously reported to be induced in a variety of cells during peripheral tissue inflammation. In the basal state, SCYA2 is highly expressed in the choroid plexus as compared to other CNS tissues. During hind paw inflammation, SCYA2 expression was significantly elevated in choroid plexus, whereas it remained unchanged in a variety of brain regions. The SCYA2-expressing cells were strongly associated with the choroid plexus as vascular depletion of blood cells by whole-body saline flush did not significantly alter SCYA2 expression in the choroid plexus. In situ hybridization suggested that the SCYA2-expressing cells were localized to the choroid plexus stroma. To elucidate potential molecular mechanisms of SCYA2 increase, we examined genes in the NF-κβ signaling cascade including TNF-α, IL-1β and IκBα in choroid tissue. Given that we also detected increased levels of MCP-1 protein by ELISA, we sought to identify potential downstream targets of MCP-1 and observed altered expression levels of mRNAs encoding tight junction proteins TJP2 and claudin 5. Finally, we detected a substantial up-regulation of the transcript encoding E-selectin, a molecule which could participate in leukocyte recruitment to the choroid plexus along with MCP-1. Together, these results suggest that profound changes occur in the choroid plexus during

A mast cell secretagogue, compound 48/80, prevents the accumulation of hyaluronan in lung tissue injured by ionizing irradiation

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Nilsson, K.; Bjermer, L.; Hellstroem, S.H.; Henriksson, R.; Haellgren, R.

1990-01-01

Irradiation with a single dose of 30 Grey on the basal regions of the lungs of Sprague-Dawley rats induced a peribronchial and alveolar inflammation. Infiltration of mast cells in the edematous alveolar interstitial tissue and also in the peribronchial tissue were characteristic features of the lesion. The appearance of mast cells was already seen 4 wk after irradiation and by weeks 6 to 8 there was a heavy infiltration. The staining properties suggested that they were connective tissue-type mast cells. The infiltration of mast cells was paralleled by an accumulation of hyaluronan (hyaluronic acid) in the alveolar interstitial tissue 6 and 8 wk after irradiation. The recovery of hyaluronan (HA) during bronchoalveolar lavage (BAL) of the lungs also increased at this time. Treatment with a mast cell secretagogue, compound 48/80, induced a distinct reduction of granulated mast cells in the alveolar tissue. Regular treatment with compound 48/80 from the time of irradiation considerably reduced the HA recovery during BAL and the HA accumulation in the interstitial tissue but did not affect the interstitial infiltration of mononuclear cells and polymorphonuclear leukocytes. By contrast, an accumulation of HA in the alveolar interstitial space was induced when compound 48/80 was given not until mast cell infiltration of the lung had started. The effects of compound 48/80 indicate that the connective tissue response after lung irradiation is dependent on whether or not mast cell degranulation is induced before or after the mast cell infiltration of the alveolar tissue

Analysis of factors causing signal loss in the measurement of lung tissue water by nuclear magnetic resonance

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Fukuzaki, Minoru; Shioya, Sumie; Haida, Munetaka

1997-01-01

The water content of lung, brain, and muscle tissue was measured by nuclear magnetic resonance (NMR) and compared with gravimetric determinations. The NMR signal intensity of water was measured by a single 90 degree pulse and by a spin-echo sequence. The absolute water content was determined by the difference in the sample's weight before and after desiccation. The NMR detectable water in each tissue was expressed as a percentage of the signal intensity for an equal weight of distilled water. Using the single pulse measurement, 67% of the gravimetrically-measured water was detected in collapsed lung samples (consisting of about 47% retained air), in contrast to 96% for brain and 98% for muscle. For degassed lung samples, the NMR detectability of water increased to 87% with the single pulse measurement and to 90% with the spin-echo measurement, but the values remained significantly less than those of brain or muscle. Factors that caused the NMR signal loss of 33% in collapsed lung samples were: air-tissue interfaces (20%), microscopic field inhomogeneity (3%), and a water component with an extremely short magnetization decay time constant (10%). (author)

Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

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Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

2015-07-01

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

Does Three-Dimensional External Beam Partial Breast Irradiation Spare Lung Tissue Compared With Standard Whole Breast Irradiation?

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Jain, Anudh K.; Vallow, Laura A.; Gale, Ashley A.; Buskirk, Steven J.

2009-01-01

Purpose: To determine whether three-dimensional conformal partial breast irradiation (3D-PBI) spares lung tissue compared with whole breast irradiation (WBI) and to include the biologically equivalent dose (BED) to account for differences in fractionation. Methods and Materials: Radiotherapy treatment plans were devised for WBI and 3D-PBI for 25 consecutive patients randomized on the NSABP B-39/RTOG 0413 protocol at Mayo Clinic in Jacksonville, Florida. WBI plans were for 50 Gy in 25 fractions, and 3D-PBI plans were for 38.5 Gy in 10 fractions. Volume of ipsilateral lung receiving 2.5, 5, 10, and 20 Gy was recorded for each plan. The linear quadratic equation was used to calculate the corresponding dose delivered in 10 fractions and volume of ipsilateral lung receiving these doses was recorded for PBI plans. Ipsilateral mean lung dose was recorded for each plan and converted to BED. Results: There was a significant decrease in volume of lung receiving 20 Gy with PBI (median, 4.4% vs. 7.5%; p 3 vs 4.85 Gy 3 , p = 0.07). PBI plans exposed more lung to 2.5 and 5 Gy. Conclusions: 3D-PBI exposes greater volumes of lung tissue to low doses of radiation and spares the amount of lung receiving higher doses when compared with WBI.

CT imaging of coexisting pulmonary tuberculosis and lung cancer

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Lv Yan; Xie Ruming; Zhou Xinhua; Zhou Zhen; Xu Jinping; He Wei; Guo Lifang; Ning Fenggang

2013-01-01

Objective: To study the CT characteristics of coexisting pulmonary tuberculosis and lung cancer. Methods: One hundred and four patients of coexisting pulmonary tuberculosis and lung cancer proved by histology, cytology or clinical underwent CT examination. All patients were divided into two groups, group Ⅰ were the patients with the lung cancer after tuberculosis or both found simultaneously (group Ⅰ a with peripheral lung cancer and group Ⅰ b with central lung cancer), group Ⅱ with tuberculosis during lung cancer chemotherapy (group Ⅱ a with peripheral lung cancer and group Ⅱ b with central lung cancer). Imaging characteristics of tuberculosis and lung cancer were compared. χ"2 test and t test were used for the statistical analysis. Results: Of 104 patients, there were 92 patients (88.5%) in group Ⅰ and 12 patients (11.5%) in group Ⅱ. Seventy patients (76.1%) of lung cancer and tuberculosis were located in the same lobe and 22 patients (23.9%) in the different lobes in group Ⅰ. There was no significant difference in distribution of tuberculosis between group Ⅰ and group Ⅱ (χ"2 = 4.302, P = 0.507). The fibrous stripes, nodules of calcification and pleural adhesion of tuberculosis were statistically significant between the two groups (χ"2 = 22.737, 15.193, 27.792, P < 0.05). There were 33 central lung cancers and 71 peripheral lung cancers. In group Ⅰ a (64 patients of peripheral lung cancers), 39 patients (60.9%) had typical manifestations and most of the lesions were ≥ 3 cm (n = 49, 76.6%), solid lesions showed variable enhancement. Conclusions: Secondary tuberculosis during lung cancer chemotherapy has the same CT characteristics with the common active tuberculosis. The morphology, enhancement pattern of lesion and follow-up are helpful for the diagnosis of lung cancer after tuberculosis. (authors)

Protective ventilation reduces Pseudomonas aeruginosa growth in lung tissue in a porcine pneumonia model.

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Sperber, Jesper; Nyberg, Axel; Lipcsey, Miklos; Melhus, Åsa; Larsson, Anders; Sjölin, Jan; Castegren, Markus

2017-08-31

Mechanical ventilation with positive end expiratory pressure and low tidal volume, i.e. protective ventilation, is recommended in patients with acute respiratory distress syndrome. However, the effect of protective ventilation on bacterial growth during early pneumonia in non-injured lungs is not extensively studied. The main objectives were to compare two different ventilator settings on Pseudomonas aeruginosa growth in lung tissue and the development of lung injury. A porcine model of severe pneumonia was used. The protective group (n = 10) had an end expiratory pressure of 10 cm H 2 O and a tidal volume of 6 ml x kg -1 . The control group (n = 10) had an end expiratory pressure of 5 cm H 2 O and a tidal volume of 10 ml x kg -1 . 10 11 colony forming units of Pseudomonas aeruginosa were inoculated intra-tracheally at baseline, after which the experiment continued for 6 h. Two animals from each group received only saline, and served as sham animals. Lung tissue samples from each animal were used for bacterial cultures and wet-to-dry weight ratio measurements. The protective group displayed lower numbers of Pseudomonas aeruginosa (p protective group was unchanged (p protective ventilation with lower tidal volume and higher end expiratory pressure has the potential to reduce the pulmonary bacterial burden and the development of lung injury.

Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

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Zhang, Ye; Lam, Chiu-Wing; Zalesak, Selina M.; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Scully, Robert R.; Williams, Kyle; Wu, Honglu; James, John T.

2014-01-01

The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

Radiation-induced changes in production of prostaglandins Fsub(2α), E, and thromboxane B2 in guinea pig parenchymal lung tissues

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Steel, L.K.; Catravas, G.N.

1982-01-01

At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2α), PGE, and thromboxane B 2 were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB 2 synthesis at 24 hours and for PGFsub(2α) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur

Clinical significance of LUNX mRNA, CK19 mRNA, CEA mRNA expression in detecting micrometastasis from lung cancer

International Nuclear Information System (INIS)

Zhu Guangying; Liu Delin; Chen Jie

2003-01-01

Objective: To evaluate the sensitivity, specificity and clinical significance of CK19 mRNA, CEA mRNA and LUNX mRNA for detecting micrometastasis by sampling the peripheral blood and regional lymph nodes of lung cancer patients. Methods: Reverse transcriptase chain reaction (RT-PCR) was used to detect LUNX mRNA, CK19 mRNA, CEA mRNA for micrometastasis by sampling the peripheral blood of 48 lung cancer patients and 44 regional lymph nodes of such patients treated by curative resection. Peripheral blood of 30 patients with pulmonary benign lesions and 10 normal healthy volunteers and lymph nodes of 6 patients with benign pulmonary diseases served as control. Results: 1) LUNX mRNA, CK19 mRNA, CEA mRNA were expressed in all (35/35) lung cancer tissues. 2) In the peripheral blood from 48 lung cancer patients, 30 (62.5%) were positive for LUNX mRNA, 24 (50.0%) positive for CK19 mRNA and 32(66.7%) positive for CEA mRNA. The positive detection rates of micrometastasis in 44 lymph nodes from lung cancer patients were 36.4% (16 out of 44) for LUNX mRNA, 27.3% (12 out of 44) for CK19 mRNA and 40.9% (18 out of 44) for CEA mRNA. 3) In the 30 blood samples from patients with pulmonary benign diseases, 2 (6.7%) expressed CK19 mRNA, but none expressed LUNX mRNA or CEA mRNA. All the 3 molecular markers were negative in the 10 blood samples from healthy volunteers. In 11 lymph nodes from patients with pulmonary benign lesions, none was positive for any of the three markers. 4) In 44 regional lymph nodes from lung cancer patients, 6 (13.6%) were positive for metastasis by histopathological examination, with a positive rate significantly lower than that of the RT-PCR (P<0.05). 5) The micrometastatic positive rate in the peripheral blood of 40 non-small cell lung cancer (NSCLC) patients was significantly related to TNM stage (P=0.01). Conclusions: LUNX mRNA, CK19 MRNA, CEA mRNA are all appropriate target genes for the detection of micrometastasis from lung cancer. LUNX mRNA and CEA m

Low or undetectable TPO receptor expression in malignant tissue and cell lines derived from breast, lung, and ovarian tumors

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Erickson-Miller Connie L

2012-09-01

Full Text Available Abstract Background Numerous efficacious chemotherapy regimens may cause thrombocytopenia. Thrombopoietin receptor (TPO-R agonists, such as eltrombopag, represent a novel approach for the treatment of chemotherapy-induced thrombocytopenia. The TPO-R MPL is expressed on megakaryocytes and megakaryocyte precursors, although little is known about its expression on other tissues. Methods Breast, lung, and ovarian tumor samples were analyzed for MPL expression by microarray and/or quantitative reverse transcription-polymerase chain reaction (qRT-PCR, and for TPO-R protein expression by immunohistochemistry (IHC. Cell line proliferation assays were used to analyze the in vitro effect of eltrombopag on breast, lung, and ovarian tumor cell proliferation. The lung carcinoma cell lines were also analyzed for TPO-R protein expression by Western blot. Results MPL mRNA was not detectable in 118 breast tumors and was detectable at only very low levels in 48% of 29 lung tumors studied by microarray analysis. By qRT-PCR, low but detectable levels of MPL mRNA were detectable in some normal (14-43% and malignant (3-17% breast, lung, and ovarian tissues. A comparison of MPL to EPOR, ERBB2, and IGF1R mRNA demonstrates that MPL mRNA levels were far lower than those of EPOR and ERBB2 mRNA in the same tissues. IHC analysis showed negligible TPO-R protein expression in tumor tissues, confirming mRNA analysis. Culture of breast, lung, and ovarian carcinoma cell lines showed no increase, and in fact, showed a decrease in proliferation following incubation with eltrombopag. Western blot analyses revealed no detectable TPO-R protein expression in the lung carcinoma cell lines. Conclusions Multiple analyses of breast, lung, and ovarian tumor samples and/or cell lines show no evidence of MPL mRNA or TPO-R protein expression. Eltrombopag does not stimulate growth of breast, lung, or ovarian tumor cell lines at doses likely to exert their actions on megakaryocytes and

Tissue ablation accelerated by peripheral scanning mode with high-intensity focused ultrasound: a study on isolated porcine liver perfusion.

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Bu, Rui; Yin, Li; Yang, Han; Wang, Qi; Wu, Feng; Zou, Jian Zhong

2013-08-01

The aims of this study were to investigate the feasibility of accelerated tissue ablation using a peripheral scanning mode with high-intensity focused ultrasound (HIFU) and to explore the effect of flow rate on total energy consumption of the target tissues. Using a model of isolated porcine liver perfusion via the portal vein and hepatic artery, we conducted a scanning protocol along the periphery of the target tissues using linear-scanned HIFU to carefully adjust the varying focal depth, generator power, scanning velocity and line-by-line interval over the entire ablation range. Porcine livers were divided into four ablation groups: group 1, n = 12, with dual-vessel perfusion; group 2, n = 11, with portal vein perfusion alone; group 3, n = 10, with hepatic artery perfusion alone; and group 4, n = 11, control group with no-flow perfusion. The samples were cut open consecutively at a thickness of 3 mm, and the actual ablation ranges were calculated along the periphery of the target tissues after triphenyl tetrazolium chloride staining. Total energy consumption was calculated as the sum of the energy requirements at various focal depths in each group. On the basis of the pre-supposed scanning protocol, the peripheral region of the target tissue formed a complete coagulation necrosis barrier in each group with varying dose combinations, and the volume of the peripheral necrotic area did not differ significantly among the four groups (p > 0.05). Furthermore, total energy consumption in each group significantly decreased with the corresponding decrease in flow rate (p Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

On Predicting lung cancer subtypes using ‘omic’ data from tumor and tumor-adjacent histologically-normal tissue

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Pineda, Arturo López; Ogoe, Henry Ato; Balasubramanian, Jeya Balaji; Rangel Escareño, Claudia; Visweswaran, Shyam; Herman, James Gordon; Gopalakrishnan, Vanathi

2016-01-01

Adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the most prevalent histological types among lung cancers. Distinguishing between these subtypes is critically important because they have different implications for prognosis and treatment. Normally, histopathological analyses are used to distinguish between the two, where the tissue samples are collected based on small endoscopic samples or needle aspirations. However, the lack of cell architecture in these small tissue samples hampers the process of distinguishing between the two subtypes. Molecular profiling can also be used to discriminate between the two lung cancer subtypes, on condition that the biopsy is composed of at least 50 % of tumor cells. However, for some cases, the tissue composition of a biopsy might be a mix of tumor and tumor-adjacent histologically normal tissue (TAHN). When this happens, a new biopsy is required, with associated cost, risks and discomfort to the patient. To avoid this problem, we hypothesize that a computational method can distinguish between lung cancer subtypes given tumor and TAHN tissue. Using publicly available datasets for gene expression and DNA methylation, we applied four classification tasks, depending on the possible combinations of tumor and TAHN tissue. First, we used a feature selector (ReliefF/Limma) to select relevant variables, which were then used to build a simple naïve Bayes classification model. Then, we evaluated the classification performance of our models by measuring the area under the receiver operating characteristic curve (AUC). Finally, we analyzed the relevance of the selected genes using hierarchical clustering and IPA® software for gene functional analysis. All Bayesian models achieved high classification performance (AUC > 0.94), which were confirmed by hierarchical cluster analysis. From the genes selected, 25 (93 %) were found to be related to cancer (19 were associated with ADC or SCC), confirming the biological relevance of our

Overexpression of IL-38 protein in anticancer drug-induced lung injury and acute exacerbation of idiopathic pulmonary fibrosis.

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Tominaga, Masaki; Okamoto, Masaki; Kawayama, Tomotaka; Matsuoka, Masanobu; Kaieda, Shinjiro; Sakazaki, Yuki; Kinoshita, Takashi; Mori, Daisuke; Inoue, Akira; Hoshino, Tomoaki

2017-09-01

Interleukin (IL)-38, a member of the IL-1 family, shows high homology to IL-1 receptor antagonist (IL-1Ra) and IL-36 receptor antagonist (IL-36Ra). Its function in interstitial lung disease (ILD) is still unknown. To determine the expression pattern of IL-38 mRNA, a panel of cDNAs derived from various tissues was analyzed by quantitative real-time PCR. Immunohistochemical reactivity with anti-human IL-38 monoclonal antibody (clone H127C) was evaluated semi-quantitatively in lung tissue samples from 12 patients with idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), 5 with acute exacerbation of IPF, and 10 with anticancer drug-induced ILD (bleomycin in 5 and epidermal growth factor receptor-tyrosine kinase inhibitor in 5). Control lung tissues were obtained from areas of normal lung in 22 lung cancer patients who underwent extirpation surgery. IL-38 transcripts were strongly expressed in the lung, spleen, synoviocytes, and peripheral blood mononuclear cells, and at a lower level in pancreas and muscle. IL-38 protein was not strongly expressed in normal pulmonary alveolar tissues in all 22 control lungs. In contrast, IL-38 was overexpressed in the lungs of 4 of 5 (80%) patients with acute IPF exacerbation and 100% (10/10) of the patients with drug-induced ILD. IL-38 overexpression was limited to hyperplastic type II pneumocytes, which are considered to reflect regenerative change following diffuse alveolar damage in ILD. IL-38 may play an important role in acute and/or chronic inflammation in anticancer drug-induced lung injury and acute exacerbation of IPF. Copyright © 2017 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

Pseudofracture: an acute peripheral tissue trauma model.

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Darwiche, Sophie S; Kobbe, Philipp; Pfeifer, Roman; Kohut, Lauryn; Pape, Hans-Christoph; Billiar, Timothy

2011-04-18

pseudofracture, as we wanted a sterile yet proportionally severe peripheral tissue trauma model. Hemorrhagic shock is a common finding in the setting of severe trauma, and the global hypoperfusion adds a very relevant element to a trauma model. The pseudofracture model can be easily combined with a hemorrhagic shock model for a multiple trauma model of high severity.

Three-dimensional simultaneous optical coherence tomography and confocal fluorescence microscopy for investigation of lung tissue.

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Gaertner, Maria; Cimalla, Peter; Meissner, Sven; Kuebler, Wolfgang M; Koch, Edmund

2012-07-01

Although several strategies exist for a minimal-invasive treatment of patients with lung failure, the mortality rate of acute respiratory distress syndrome still reaches 30% at minimum. This striking number indicates the necessity of understanding lung dynamics on an alveolar level. To investigate the dynamical behavior on a microscale, we used three-dimensional geometrical and functional imaging to observe tissue parameters including alveolar size and length of embedded elastic fibers during ventilation. We established a combined optical coherence tomography (OCT) and confocal fluorescence microscopy system that is able to monitor the distension of alveolar tissue and elastin fibers simultaneously within three dimensions. The OCT system can laterally resolve a 4.9 μm line pair feature and has an approximately 11 μm full-width-half-maximum axial resolution in air. confocal fluorescence microscopy visualizes molecular properties of the tissue with a resolution of 0.75 μm (laterally), and 5.9 μm (axially) via fluorescence detection of the dye sulforhodamine B specifically binding to elastin. For system evaluation, we used a mouse model in situ to perform lung distension by application of different constant pressure values within the physiological regime. Our method enables the investigation of alveolar dynamics by helping to reveal basic processes emerging during artificial ventilation and breathing.

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

International Nuclear Information System (INIS)

Rangel, M.P.; Sá, V.K. de; Martins, V.; Martins, J.R.M.; Parra, E.R.; Mendes, A.; Andrade, P.C.; Reis, R.M.; Longatto-Filho, A.; Oliveira, C.Z.; Takagaki, T.; Carraro, D.M.; Nader, H.B.; Capelozzi, V.L.

2015-01-01

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Energy Technology Data Exchange (ETDEWEB)

Rangel, M.P.; Sá, V.K. de; Martins, V. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Martins, J.R.M. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Disciplina de Endocrinologia e Metabolismo, Laboratório de Endocrinologia Molecular e Translacional-LEMT, Departamento de Medicina, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Parra, E.R. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Mendes, A. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Andrade, P.C. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Reis, R.M. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Longatto-Filho, A. [Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Guimarães (Portugal); Laboratório de Investigação Médica (LIM 14), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Oliveira, C.Z. [Centro de Pesquisa em Oncologia Molecular, Hospital de Câncer de Barretos, Fundação Pio XII, Barretos, SP (Brazil); Takagaki, T. [Divisão de Pneumologia, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Carraro, D.M. [Centro Internacional de Pesquisa/CIPE, AC Camargo Cancer Center, São Paulo, SP (Brazil); Nader, H.B. [Disciplina de Biologia Molecular, Departamento de Bioquímica, Faculdade de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Capelozzi, V.L. [Departamento de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2015-05-08

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.

Peripheral blood stem cell harvest in patients with limited stage small-cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Katakami, Nobuyuki; Takakura, Shunji; Fujii, Hiroshi; Nishimura, Takashi; Umeda, Bunichi [Kobe City General Hospital (Japan)

2000-06-01

Chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood stem cells (PBSC) was performed in patients with limited stage small-cell lung cancer. Chemotherapy consisted of cisplatin/etoposide or cisplatin/adriamycin/etoposide. The amounts of CD34 positive cells and granulocyte-macrophage colony forming units (CFU-GM) collected during 2-3 courses of apheresis were 3.1{+-}2.9 x 10{sup 6}/kg (n=10) and 3.1{+-}1.5 x 10{sup 5}/kg (n=8) , respectively. Adequate amounts of PBSC were also harvested even in patients treated with concurrent chemoradiotherapy. Eight patients were successfully treated with high-dose chemotherapy consisting of ifosfamide, carboplatin and etoposide with PBSC transfusion. The patients'-bone marrow reconstruction was rapid and no treatment-related death was observed. (author)

Age-dependent accumulation of heavy metals in liver, kidney and lung tissues of homing pigeons in Beijing, China.

Science.gov (United States)

Cui, Jia; Wu, Bin; Halbrook, Richard S; Zang, Shuying

2013-12-01

Biomonitoring provides direct evidence of the bioavailability and accumulation of toxic elements in the environment. In the current study, 1-2, 5-6, and 9-10+ year old homing pigeons collected from the Haidian District of Beijing during 2011 were necropsied and concentrations of cadmium, lead, and mercury were measured in liver, lung, and kidney tissue. At necropsy, gray/black discoloration of the margins of the lungs was observed in 98 % of the pigeons. There were no significant differences in metal concentrations as a function of gender. Cadmium concentrations in all tissues and Pb concentrations in the lung tissues were significantly greater in 9-10+ year old pigeons compared to other age groups indicating that Cd and Pb were bioavailable. Mercury concentrations were not significantly different among age groups. Cadmium concentrations in kidney and lung tissues of 9-10+ year old pigeons were similar to or exceeded concentrations of Cd reported in pigeons from another high traffic urban area and most wild avian species from Korea suggesting that Cd in this region of Beijing may be of concern. Homing pigeons provide valuable exposure and bioaccumulation data not readily available from air monitoring alone, thus providing information regarding potential health effects in wildlife and humans in urban areas. As environmental quality standards are implemented in China, homing pigeons will serve as a valuable bio-monitor of the efficacy of these actions.

Quantification of heterogeneity in lung disease with image-based pulmonary function testing.

Science.gov (United States)

Stahr, Charlene S; Samarage, Chaminda R; Donnelley, Martin; Farrow, Nigel; Morgan, Kaye S; Zosky, Graeme; Boucher, Richard C; Siu, Karen K W; Mall, Marcus A; Parsons, David W; Dubsky, Stephen; Fouras, Andreas

2016-07-27

Computed tomography (CT) and spirometry are the mainstays of clinical pulmonary assessment. Spirometry is effort dependent and only provides a single global measure that is insensitive for regional disease, and as such, poor for capturing the early onset of lung disease, especially patchy disease such as cystic fibrosis lung disease. CT sensitively measures change in structure associated with advanced lung disease. However, obstructions in the peripheral airways and early onset of lung stiffening are often difficult to detect. Furthermore, CT imaging poses a radiation risk, particularly for young children, and dose reduction tends to result in reduced resolution. Here, we apply a series of lung tissue motion analyses, to achieve regional pulmonary function assessment in β-ENaC-overexpressing mice, a well-established model of lung disease. The expiratory time constants of regional airflows in the segmented airway tree were quantified as a measure of regional lung function. Our results showed marked heterogeneous lung function in β-ENaC-Tg mice compared to wild-type littermate controls; identified locations of airway obstruction, and quantified regions of bimodal airway resistance demonstrating lung compensation. These results demonstrate the applicability of regional lung function derived from lung motion as an effective alternative respiratory diagnostic tool.

Peripheral Vestibular System Disease in Vestibular Schwannomas

DEFF Research Database (Denmark)

Møller, Martin Nue; Hansen, Søren; Caye-Thomasen, Per

2015-01-01

density of the peripheral vestibular nerve branches, and atrophy of the neuroepithelium of the vestibular end organs. In cases with small tumors, peripheral disease occurred only in the tissue structures innervated by the specific nerve from which the tumor originated. CONCLUSION: Vestibular schwannomas...... are associated with distinctive disease of the peripheral vestibular tissue structures, suggesting anterograde degeneration and that dizziness in these patients may be caused by deficient peripheral vestibular nerve fibers, neurons, and end organs. In smaller tumors, a highly localized disease occurs, which...

Peripheral-type benzodiazepine receptors in bronchoalveolar lavage cells of patients with interstitial lung disease

International Nuclear Information System (INIS)

Branley, Howard M.; Bois, Roland M. du; Wells, Athol U.; Jones, Hazel A.

2007-01-01

Introduction: PK11195 is a ligand with high affinity for peripheral benzodiazepine receptors (PBRs), which are present in large numbers in macrophages. PBRs play a role in antioxidant pathways and apoptosis, key factors in control of lung health. Intrapulmonary PBRs, assessed in vivo by positron emission tomography (PET), are decreased in interstitial lung disease (ILD) despite increased macrophage numbers. We wished to ascertain whether the observed decrease in in vivo expression of PBRs in the PET scans could be accounted for by a reduction in PBRs per cell by saturation-binding assays of R-PK11195 in cells obtained by bronchoalveolar lavage (BAL). Methods: We performed receptor saturation-binding assays with [ 3 H]-R-PK11195 on a mixed population of cells recovered by BAL to quantify the number of R-PK11195 binding sites per macrophage in 10 subjects with ILD and 10 normal subjects. Results: Receptor affinity [dissociation constant (Kd)] was similar in ILD patients and controls. However, R-PK11195 binding sites per cell [(maximal binding sites available (B max )] were decreased in macrophages obtained by BAL from subjects with ILD compared to normal (P<.0005). Microautoradiography confirmed localization of R-PK11195 to macrophages in a mixed inflammatory cell population obtained by BAL. Conclusion: These results demonstrate that in vitro PBR expression per cell on macrophages obtained by BAL is reduced in patients with ILD indicating a potentially functionally different macrophage phenotype. As PBRs are involved in the orchestration of lung inflammatory responses, this finding offers further insight into the role of macrophages in the pathogenesis of ILDs and offers a potential avenue for pharmacological strategy

Precision cut lung slices as an efficient tool for in vitro lung physio-pharmacotoxicology studies.

Science.gov (United States)

Morin, Jean-Paul; Baste, Jean-Marc; Gay, Arnaud; Crochemore, Clément; Corbière, Cécile; Monteil, Christelle

2013-01-01

1.We review the specific approaches for lung tissue slices preparation and incubation systems and the research application fields in which lung slices proved to be a very efficient alternative to animal experimentation for biomechanical, physiological, pharmacological and toxicological approaches. 2.Focus is made on air-liquid interface dynamic organ culture systems that allow direct tissue exposure to complex aerosol and that best mimic in vivo lung tissue physiology. 3.A compilation of research applications in the fields of vascular and airway reactivity, mucociliary transport, polyamine transport, xenobiotic biotransformation, chemicals toxicology and complex aerosols supports the concept that precision cut lung slices are a very efficient tool maintaining highly differentiated functions similar to in vivo lung organ when kept under dynamic organ culture. They also have been successfully used for lung gene transfer efficiency assessment, for lung viral infection efficiency assessment, for studies of tissue preservation media and tissue post-conditioning to optimize lung tissue viability before grafting. 4.Taken all together, the reviewed studies point to a great interest for precision cut lung slices as an efficient and valuable alternative to in vivo lung organ experimentation.

Acute effects of thoracic irradiation on lung function and structure in awake sheep

International Nuclear Information System (INIS)

Loyd, J.E.; Bolds, J.M.; Sheller, J.R.; Duke, S.S.; Gillette, A.W.; Malcolm, A.W.; Meyrick, B.O.; Brigham, K.L.

1987-01-01

To investigate the acute physiological and structural changes after lung irradiation, the effects of whole-lung irradiation were investigated in fourteen sheep. Ten sheep were prepared with vascular and chronic lung lymph catheters, then a week later were given 1,500 rad whole-lung radiation and monitored for 2 days. Four sheep were given the same dose of radiation and were killed 4 h later for structural studies. Lung lymph flow increased at 3 h after radiation (14.6 +/- 2.1 ml/h) to twice the base-line flow rate (7.5 +/- 1.3), with a high lymph-to-plasma protein concentration. Pulmonary arterial pressure increased twofold from base line (18 +/- 1.6 cmH2O) at 2 h after radiation (33 +/- 3.8). Cardiac output and systemic pressure in the aorta did not change after lung radiation. Arterial O 2 tension decreased from 85 +/- 3 to 59 +/- 4 Torr at 1 day after radiation. Lymphocyte counts in both blood and lung lymph decreased to a nadir by 4 h and remained low. Thromboxane B2 concentration in lung lymph increased from base line (0.07 +/- 0.03 ng/ml) to peak at 3 h after radiation (8.2 +/- 3.7 ng/ml). The structural studies showed numerous damaged lymphocytes in the peripheral lung and bronchial associated lymphoid tissue. Quantitative analysis of the number of granulocytes in peripheral lung showed no significant change (base line 6.2 +/- 0.8 granulocytes/100 alveoli, 4 h = 10.3 +/- 2.3). The most striking change involved lung airways. The epithelial lining of the majority of airways from intrapulmonary bronchus to respiratory bronchiolus revealed damage with the appearance of intracellular and intercellular cell fragments and granules. This new large animal model of acute radiation lung injury can be used to monitor physiological, biochemical, and morphological changes after lung radiation. It is relevant to the investigation of diffuse oxidant lung injury as well as to radiobiology per se

Protective effect of gel form of gastric gavage applicated aloe vera on ischemia reperfusion injury in renal and lung tissue.

Science.gov (United States)

Sahin, Hasan; Yener, Ali Umit; Karaboga, Ihsan; Sehitoglu, Muserref Hilal; Dogu, Tugba; Altinisik, Hatice Betul; Altinisik, Ugur; Simsek, Tuncer

2017-12-30

The aloe vera plant has become increasingly popular in recent years. This study aimed to research the effect of aloe vera to prevent renal and lung tissue damage in an experimental ischemia-reperfusion (I/R) injury model. The study included 21 male Wistar Albino rats, which were categorized into control group, n = 7 (no procedures), Sham group n = 7 (I/R); and aloe vera therapy group, n = 7 (aloe vera and I/R). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were evaluated from lung and kidney tissues for biochemical investigations. As histopathological, hematoxylin and eosin and anti-iNOS were also examined. In biochemical investigations, SOD, CAT, and GPx levels of the Sham group were found to be lower compared with the other groups (P < 0.05). The aloe vera therapy group was not statistically different from control groups but significantly different compared with the Sham group. In the same way, the MDA levels of kidney and lung tissues were statistically significant in the aloe vera therapy group, compared to the Sham group. In the Sham group, the peribronchial and perialveolar edema were observed in lung parenchyma. Also, excess interstitial hemorrhage, leukocyte infiltration, and alveolar wall thickening were identified in ischemic groups. The histopathological changes were much lighter than in the aloe vera therapy group. In renal tissues, excess epithelial cell deterioration, tubular desqumination, and glomerular atrophy were observed in the Sham group. The histopathological changes were markedly reduced in the aloe vera therapy  group. In the kidney and lung tissue, the level of iNOS activity in the Sham group was significantly higher than in the control and aloe vera therapy group. This study indicated that aloe vera is protective against oxidative damage formed by I/R in distant organs like the lungs and kidneys.

Leptin receptor in peripheral adipose tissues of obese subjects

International Nuclear Information System (INIS)

Du Tongxin; Sun Junjiang; Wang Zizheng; Wang Shukui; Fu Lei; Han Liu

2002-01-01

Objective: To investigate the relationship between leptin receptor and obesity by studying the leptin receptor density B max and dissociation constant K d in peripheral adipose tissue in subjects with different body weight mass (BMI). Methods: Leptin receptor density B max and K d were assayed via radioligand method in 71 cases, including 32 classified as obese, 19 over-weight and 20 normal control. Results: With the escalating of BMI, the leptin receptor density significantly decreased in obese and over-weight group compared with that in normal control (both P d values were of no differences among all three groups suggesting no correlation between the binding ability of leptin to its receptor and BMI. A negative correlation between BMI and B max (r=-0.76, P<0.01) displayed after all. Conclusion: Leptin receptor density correlates with the BMI in obese cases and it suggests that the down-regulation of leptin receptor may contribute to the occurrence of leptin resistance and obesity after-wards

Melatonin membrane receptors in peripheral tissues: Distribution and functions

Science.gov (United States)

Slominski, Radomir M.; Reiter, Russel J.; Schlabritz-Loutsevitch, Natalia; Ostrom, Rennolds S.; Slominski, Andrzej T.

2012-01-01

Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes. PMID:22245784

Hydrogels for lung tissue engineering: Biomechanical properties of thin collagen-elastin constructs.

Science.gov (United States)

Dunphy, Siobhán E; Bratt, Jessica A J; Akram, Khondoker M; Forsyth, Nicholas R; El Haj, Alicia J

2014-10-01

In this study, collagen-elastin constructs were prepared with the aim of producing a material capable of mimicking the mechanical properties of a single alveolar wall. Collagen has been used in a wide range of tissue engineering applications; however, due to its low mechanical properties its use is limited to non load-bearing applications without further manipulation using methods such as cross-linking or mechanical compression. Here, it was hypothesised that the addition of soluble elastin to a collagen hydrogel could improve its mechanical properties. Hydrogels made from collagen only and collagen plus varying amounts elastin were prepared. Young׳s modulus of each membrane was measured using the combination of a non-destructive indentation and a theoretical model previously described. An increase in Young׳s modulus was observed with increasing concentration of elastin. The use of non-destructive indentation allowed for online monitoring of the elastic moduli of cell-seeded constructs over 8 days. The addition of lung fibroblasts into the membrane increased the stiffness of the hydrogels further and cell-seeded collagen hydrogels were found to have a stiffness equal to the theoretical value for a single alveolar wall (≈5kPa). Through provision of some of the native extracellular matrix components of the lung parenchyma these scaffolds may be able to provide an initial building block toward the regeneration of new functional lung tissue. Copyright © 2014 Elsevier Ltd. All rights reserved.

Expression and clinical significance of NF-毷B, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy

Directory of Open Access Journals (Sweden)

Cheng-Luo Hao

2016-06-01

Full Text Available Objective: To study the expression and clinical significance of NF-kB, CTGF and OPN in mononuclear cells in peripheral blood as well as renal tissues in patients with IgA nephropathy. Methods: A total of 25 nephropathy patients diagnosed with IgA nephropathy and 25 patients receiving nephrectomy due to trauma or tumor in our hospital were studied. Peripheral blood and kidney tissues were collected to test NF-kB, CTGF, OPN, T-bet, GATA-3, RORγT and Foxp3 expressions. Results: CTGF and OPN percentages in peripheral blood mononuclear cells and kidney tissues of nephropathy patients were higher than those of the control group. NF-kB, CTGF and OPN expressions were significantly higher in M1, E1, S1 group patients’ peripheral blood mononuclear cells and renal tissues than those in M0, E1 and S1 group. T-bet, GATA-3 and RORγT expressions in nephropathy patients’ peripheral blood were significantly higher than those in the control group, and were positively correlated with NF-kB, CTGF and OPN expressions. The expression of Foxp3 was significantly lower than that of control group, and was negatively correlated with NF-kB, CTGF and OPN expressions. Conclusions: The expression of NF-kB, CTGF and OPN in peripheral blood mononuclear cells and renal tissue in patients with IgA nephropathy is abnormally high and can evaluate the prognosis of the disease and the differentiation of CD4+T cells.

Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation

Science.gov (United States)

2012-01-01

Background Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in part are responsible for tissue damage during disease progression. Thus, we hypothesized that a MMP-9/-12 generated fragment of elastin may be a relevant biochemical maker for lung diseases. Methods Elastin fragments were identified by mass-spectrometry and one sequence, generated by MMP-9 and -12 (ELN-441), was selected for monoclonal antibody generation and used in the development of an ELISA. Soluble and insoluble elastin from lung was cleaved in vitro and the time-dependent release of fragments was assessed in the ELN-441 assay. The release of ELN-441 in human serum from patients with chronic obstructive pulmonary disease (COPD) (n = 10) and idiopathic pulmonary fibrosis (IPF) (n = 29) were compared to healthy matched controls (n = 11). Results The sequence ELN-441 was exclusively generated by MMP-9 and -12 and was time-dependently released from soluble lung elastin. ELN-441 levels were 287% higher in patients diagnosed with COPD (p elastin. This fragment was elevated in serum from patients with the lung diseases IPF and COPD, however these data needs to be validated in larger clinical settings. PMID:22818364

DNA methylation changes measured in pre‐diagnostic peripheral blood samples are associated with smoking and lung cancer risk

Science.gov (United States)

Baglietto, Laura; Ponzi, Erica; Haycock, Philip; Hodge, Allison; Bianca Assumma, Manuela; Jung, Chol‐Hee; Chung, Jessica; Fasanelli, Francesca; Guida, Florence; Campanella, Gianluca; Chadeau‐Hyam, Marc; Grankvist, Kjell; Johansson, Mikael; Ala, Ugo; Provero, Paolo; Wong, Ee Ming; Joo, Jihoon; English, Dallas R.; Kazmi, Nabila; Lund, Eiliv; Faltus, Christian; Kaaks, Rudolf; Risch, Angela; Barrdahl, Myrto; Sandanger, Torkjel M.; Southey, Melissa C.; Giles, Graham G.; Johansson, Mattias; Vineis, Paolo; Polidoro, Silvia; Relton, Caroline L.

2016-01-01

DNA methylation changes are associated with cigarette smoking. We used the Illumina Infinium HumanMethylation450 array to determine whether methylation in DNA from pre‐diagnostic, peripheral blood samples is associated with lung cancer risk. We used a case‐control study nested within the EPIC‐Italy cohort and a study within the MCCS cohort as discovery sets (a total of 552 case‐control pairs). We validated the top signals in 429 case‐control pairs from another 3 studies. We identified six CpGs for which hypomethylation was associated with lung cancer risk: cg05575921 in the AHRR gene (p‐valuepooled = 4 × 10−17), cg03636183 in the F2RL3 gene (p‐valuepooled = 2 × 10 − 13), cg21566642 and cg05951221 in 2q37.1 (p‐valuepooled = 7 × 10−16 and 1 × 10−11 respectively), cg06126421 in 6p21.33 (p‐valuepooled = 2 × 10−15) and cg23387569 in 12q14.1 (p‐valuepooled = 5 × 10−7). For cg05951221 and cg23387569 the strength of association was virtually identical in never and current smokers. For all these CpGs except for cg23387569, the methylation levels were different across smoking categories in controls (p‐valuesheterogeneity ≤ 1.8 x10 − 7), were lowest for current smokers and increased with time since quitting for former smokers. We observed a gain in discrimination between cases and controls measured by the area under the ROC curve of at least 8% (p‐values ≥ 0.003) in former smokers by adding methylation at the 6 CpGs into risk prediction models including smoking status and number of pack‐years. Our findings provide convincing evidence that smoking and possibly other factors lead to DNA methylation changes measurable in peripheral blood that may improve prediction of lung cancer risk. PMID:27632354

Radiation-induced changes in production of prostaglandins Fsub(2. cap alpha. ), E, and thromboxane B/sub 2/ in guinea pig parenchymal lung tissues

Energy Technology Data Exchange (ETDEWEB)

Steel, L K; Catravas, G N [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

1982-11-01

At 1 hour to 4 days after unilateral exposure of guinea pigs to a single dose (0.5, 1.5, or 3.0 Gy) of gamma-radiation, changes were detected in prostaglandin and thromboxane concentrations in parenchymal lung tissues. At 1-3 hours after exposure, tissue levels of PGFsub(2..cap alpha..), PGE, and thromboxane B/sub 2/ were significantly elevated in animals receiving 3.0 Gy, with the magnitude of alteration revealing a radiation dose effect. By 24 hours, tissue prostaglandin and thromboxane levels returned to near control values. Lung tissue synthesis of prostaglandins in response to H-1 receptor stimulation by the exogenous addition of histamine revealed similar radiation dose effects. The carboxylic acid ionophore A23187, exogenously applied to lung tissues, revealed a transient peak of increased sensitivity to ionophore stimulation for TxB/sub 2/ synthesis at 24 hours and for PGFsub(2..cap alpha..) at 72 hours post-irradiation. The data suggest that significant alterations in prostaglandin and thromboxane concentrations in parenchymal lung tissues occur following irradiation, in a dose-dependent manner, and that altered responsiveness to H-1 receptor stimulation and divalent cation transport also occur.

Lung vitamin E transport processes are affected by both age and environmental oxidants in mice

International Nuclear Information System (INIS)

Valacchi, Giuseppe; Vasu, Vihas T.; Yokohama, Wallace; Corbacho, Ana M.; Phung, Anh; Lim, Yunsook; Aung, Hnin Hnin; Cross, Carroll E.; Davis, Paul A.

2007-01-01

Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies the effects of age and two environmental oxidants ozone (O 3 ) (0.25 ppm 6 h/day) and cigarette smoke (CS) (60 mg/m 3 6 h/day) for 4 days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (p 3 or CS at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, CD36, ATP binding cassette 3 (ABCA3) and ABCA1 and protein levels, determined by Western blots for SRB1, ATTP and ABCA1 were assessed. Aged mouse lung showed a lower levels of ATTP, ABCA3 and SRB1 and a higher level CD36 and ABCA1. Acute exposure to either O 3 or CS induced declines in ATTP and SRB1 in both aged and young mice lung. CD36 increased in both young and aged mice lung upon exposure to O 3 and CS. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types

Interobserver delineation variation in lung tumour stereotacticbody radiotherapy

DEFF Research Database (Denmark)

Persson, G. F.; Nygaard, D. E.; Hollensen, Christian

2012-01-01

the interobserver delineation variation for stereotactic body radiotherapy (SBRT) of peripheral lung tumours using a cross-sectional study design. Methods 22 consecutive patients with 26 tumours were included. Positron emission tomography/CT scans were acquired for planning of SBRT. Three oncologists and three......-sectional analysis of delineation variation for peripheral lung tumours referred for SBRT, establishing the evidence that interobserver variation is very small for these tumours....

Silica inhalation altered telomere length and gene expression of telomere regulatory proteins in lung tissue of rats.

Science.gov (United States)

Shoeb, Mohammad; Joseph, Pius; Kodali, Vamsi; Mustafa, Gul; Farris, Breanne Y; Umbright, Christina; Roberts, Jenny R; Erdely, Aaron; Antonini, James M

2017-12-11

Exposure to silica can cause lung fibrosis and cancer. Identification of molecular targets is important for the intervention and/or prevention of silica-induced lung diseases. Telomeres consist of tandem repeats of DNA sequences at the end of chromosomes, preventing chromosomal fusion and degradation. Regulator of telomere length-1 (RTEL1) and telomerase reverse transcriptase (TERT), genes involved in telomere regulation and function, play important roles in maintaining telomere integrity and length. The goal of this study was to assess the effect of silica inhalation on telomere length and the regulation of RTEL1 and TERT. Lung tissues and blood samples were collected from rats at 4, 32, and 44 wk after exposure to 15 mg/m 3 of silica × 6 h/d × 5 d. Controls were exposed to air. At all-time points, RTEL1 expression was significantly decreased in lung tissue of the silica-exposed animals compared to controls. Also, significant increases in telomere length and TERT were observed in the silica group at 4 and 32 wk. Telomere length, RTEL1 and TERT expression may serve as potential biomarkers related to silica exposure and may offer insight into the molecular mechanism of silica-induced lung disease and tumorigeneses.

X-Ray longitudinal and computed tomography in the diagnosis of peripheral tumor-like formations of the lungs

International Nuclear Information System (INIS)

Sokolov, V.A.; Kartashov, V.M.; Piven', A.I.; Krasnoborova, S.Yu.; Blinova, L.V.; Savel'ev, A.V.

1997-01-01

Fifty eight patients with peripheral tumor-like formations of the lung (33 with cancer and 25 with benign formations) were examined by longitudinal tomography and CT. The potentialities f the two techniques in detecting the major semiotic signs of cancer and malignant formations were compared. The main or major signs, such as the shape of shadow and the pattern of outlines, which make it possible to differentiate bening and malignant formations, are virtually equally imaged by the two techniques. CT is superior to X-ray longitudinal tomography in revealing minor calcifications and microdestructions, hyperplastic intrathoracic lymph nodes. The significance of some symptoms for differential diagnosis calls for further clarification

Pulmonary infiltration with eosinophilia complicated with mucosa-associated lymphoid tissue lymphoma: A case report.

Science.gov (United States)

Liu, Yin; Tangsun, Yinyan; Xiao, Yonglong; Zhang, Deping; Cao, Min

2016-09-01

Tissue eosinophilia is rarely observed in cases of non-Hodgkin's lymphoma of B cell origin. The present study describes a rare case of mucosa-associated lymphoid tissue (MALT) lymphoma, which was initially misdiagnosed as eosinophilic pneumonia. The initial diagnosis was formed based on the results of chest radiography, peripheral eosinophilia tests and bronchoalveolar lavage, and the clinical course of the patient. Following administration of methylprednisolone (40 mg/day) for 4 days and oral administration of prednisolone (30 mg/day), the clinical course rapidly improved and the eosinophil count immediately decreased a to normal level. However, abnormal shadows observed on computed tomography (CT) scans of the chest did not diminish. At 6 months after the initiation of treatment, CT-guided percutaneous lung biopsy was performed, and a final diagnosis of primary pulmonary mucosa-associated lymphoid tissue lymphoma was made based on immunohistochemical examination. Primary lung MALT lymphoma remains a rare entity, with an indolent course and a reasonably favorable prognosis, whose diagnosis may be challenging.

Optimization of CT image reconstruction algorithms for the lung tissue research consortium (LTRC)

Science.gov (United States)

McCollough, Cynthia; Zhang, Jie; Bruesewitz, Michael; Bartholmai, Brian

2006-03-01

To create a repository of clinical data, CT images and tissue samples and to more clearly understand the pathogenetic features of pulmonary fibrosis and emphysema, the National Heart, Lung, and Blood Institute (NHLBI) launched a cooperative effort known as the Lung Tissue Resource Consortium (LTRC). The CT images for the LTRC effort must contain accurate CT numbers in order to characterize tissues, and must have high-spatial resolution to show fine anatomic structures. This study was performed to optimize the CT image reconstruction algorithms to achieve these criteria. Quantitative analyses of phantom and clinical images were conducted. The ACR CT accreditation phantom containing five regions of distinct CT attenuations (CT numbers of approximately -1000 HU, -80 HU, 0 HU, 130 HU and 900 HU), and a high-contrast spatial resolution test pattern, was scanned using CT systems from two manufacturers (General Electric (GE) Healthcare and Siemens Medical Solutions). Phantom images were reconstructed using all relevant reconstruction algorithms. Mean CT numbers and image noise (standard deviation) were measured and compared for the five materials. Clinical high-resolution chest CT images acquired on a GE CT system for a patient with diffuse lung disease were reconstructed using BONE and STANDARD algorithms and evaluated by a thoracic radiologist in terms of image quality and disease extent. The clinical BONE images were processed with a 3 x 3 x 3 median filter to simulate a thicker slice reconstructed in smoother algorithms, which have traditionally been proven to provide an accurate estimation of emphysema extent in the lungs. Using a threshold technique, the volume of emphysema (defined as the percentage of lung voxels having a CT number lower than -950 HU) was computed for the STANDARD, BONE, and BONE filtered. The CT numbers measured in the ACR CT Phantom images were accurate for all reconstruction kernels for both manufacturers. As expected, visual evaluation of the

Post-mortem detection of gasoline residues in lung tissue and heart blood of fire victims.

Science.gov (United States)

Pahor, Kevin; Olson, Greg; Forbes, Shari L

2013-09-01

The purpose of this study was to determine whether gasoline residues could be detected post-mortem in lung tissue and heart blood of fire victims. The lungs and heart blood were investigated to determine whether they were suitable samples for collection and could be collected without contamination during an autopsy. Three sets of test subjects (pig carcasses) were investigated under two different fire scenarios. Test subjects 1 were anaesthetized following animal ethics approval, inhaled gasoline vapours for a short period and then euthanized. The carcasses were clothed and placed in a house where additional gasoline was poured onto the carcass post-mortem in one fire, but not in the other. Test subjects 2 did not inhale gasoline, were clothed and placed in the house and had gasoline poured onto them in both fires. Test subjects 3 were clothed but had no exposure to gasoline either ante- or post-mortem. Following controlled burns and suppression with water, the carcasses were collected, and their lungs and heart blood were excised at a necropsy. The headspace from the samples was analysed using thermal desorption-gas chromatography-mass spectroscopy. Gasoline was identified in the lungs and heart blood from the subjects that were exposed to gasoline vapours prior to death (test subjects 1). All other samples were negative for gasoline residues. These results suggest that it is useful to analyse for volatile ignitable liquids in lung tissue and blood as it may help to determine whether a victim was alive and inhaling gases at the time of a fire.

Incomplete Memories: The Natural Suppression of Tissue-Resident Memory CD8 T Cells in the Lung

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Katie L. Reagin

2018-01-01

Full Text Available The yearly, cyclic impact of viruses like influenza on human health and the economy is due to the high rates of mutation of traditional antibody targets, which negate any preexisting humoral immunity. However, the seasonality of influenza infections can equally be attributed to an absent or defective memory CD8 T cell response since the epitopes recognized by these cells are derived from essential virus proteins that mutate infrequently. Experiments in mouse models show that protection from heterologous influenza infection is temporally limited and conferred by a population of tissue-resident memory (TRM cells residing in the lung and lung airways. TRM are elicited by a diverse set of pathogens penetrating mucosal barriers and broadly identified by extravascular staining and expression of the activation and adhesion molecules CD69 and CD103. Interestingly, lung TRM fail to express these molecules, which could limit tissue retention, resulting in airway expulsion or death with concomitant loss of heterologous protection. Here, we make the case that respiratory infections uniquely evoke a form of natural immunosuppression whereby specific cytokines and cell–cell interactions negatively impact memory cell programming and differentiation. Respiratory memory is not only short-lived but most of the memory cells in the lung parenchyma may not be bona fide TRM. Given the quantity of microbes humans inhale over a lifetime, limiting cellular residence could be a mechanism employed by the respiratory tract to preserve organismal vitality. Therefore, successful efforts to improve respiratory immunity must carefully and selectively breach these inherent tissue barriers.

Feeding cycle-dependent circulating insulin fluctuation is not a dominant Zeitgeber for mouse peripheral clocks except in the liver: Differences between endogenous and exogenous insulin effects.

Science.gov (United States)

Oishi, Katsutaka; Yasumoto, Yuki; Higo-Yamamoto, Sayaka; Yamamoto, Saori; Ohkura, Naoki

2017-01-29

The master clock in the suprachiasmatic nucleus synchronizes peripheral clocks via humoral and neural signals in mammals. Insulin is thought to be a critical Zeitgeber (synchronizer) for peripheral clocks because it induces transient clock gene expression in cultured cells. However, the extent to which fluctuations in feeding-dependent endogenous insulin affect the temporal expression of clock genes remains unclear. We therefore investigated the temporal expression profiles of clock genes in the peripheral tissues of mice fed for 8 h during either the daytime (DF) or the nighttime (NF) for one week to determine the involvement of feeding cycle-dependent endogenous insulin rhythms in the circadian regulation of peripheral clocks. The phase of circulating insulin fluctuations was reversed in DF compared with NF mice, although those of circulating corticosterone fluctuations and nocturnal locomotor activity were identical between these mice. The reversed feeding cycle affected the circadian phases of Per1 and Per2 gene expression in the liver and not in heart, lung, white adipose and skeletal muscle tissues. On the other hand, injected exogenous insulin significantly induced Akt phosphorylation in the heart and skeletal muscle as well as the liver, and significantly induced Per1 and Per2 gene expression in all examined tissues. These findings suggest that feeding cycles and feeding cycle-dependent endogenous insulin fluctuations are not dominant entrainment signals for peripheral clocks other than the liver, although exogenous insulin might reset peripheral oscillators in mammals. Copyright © 2016 Elsevier Inc. All rights reserved.

Histone deacetylase activity is decreased in peripheral blood monocytes in patients with COPD

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Chen Yanwei

2012-03-01

Full Text Available Abstract Background Histone deacetylase (HDAC is an enzyme that regulates chromatin structure and inflammatory gene expression. In patients with chronic obstructive pulmonary disease (COPD, while accumulating evidence indicates that the activity of HDAC is decreased in lung tissue alveolar macrophages, HDAC activity in peripheral inflammatory cells has not yet been evaluated in detail. Methods HDAC activities in peripheral blood mononuclear cells (PBMC were investigated in patients with stable COPD (n = 26, non-smoking controls (n = 13, and smoking controls (n = 10, respectively. HDAC activity was measured using an HDAC Activity/Inhibitor Screening Assay Kit. Serum interleukine-8 (CXCL8 levels were determined by ELISA techniques. Lung function test was carried out according to the ATS/ERS guidelines. Results Compared with healthy non-smokers, HDAC activity in the PBMCs of COPD patients was decreased by 40% (13.06 ± 5.95 vs. 21.39 ± 4.92 (μM/μg, p Moreover, serum CXCL8 levels in patients with COPD were significantly higher than that in controls and were negatively correlated to HDAC activities. Conclusion In patients with COPD, HDAC activity in the PBMCs is lower than that in healthy controls. The reduction of HDAC activity may be associated with smoking exposure through inflammatory pathways.

Effect of radon and its progeny on the expression and mutation of p53 in lung tissues of mice

International Nuclear Information System (INIS)

Piao Chunnan; Tian Mei; Liu Jianxiang; Ruan Jianlei; Su Xu

2010-01-01

Objective: To explore the effect of radon and its progeny on the expression and mutations of p53 in lung tissue of mouse model. Methods: Apoptosis was detected by terminal deoxynucleotidy transferase-mediated dUTP-biotin nick end labeling. The expression of p53 gene was analyzed by immunohistochemistry, Western blot and realtime-PCR. PCR-SSCP was used to detect the mutation of p53 in lung tissues. Results: Compared with those in the control group, the apoptotic index were increased significantly in 30 WLM and 60 WLM groups (t=18.11, -10.30, P<0.05). The p53 protein was increased significantly (t=-11.08, P<0.05; t=-7.00, P<0.05) in 30 WLM and 60 WLM groups. The mutation of p53 gene was not detected in lungs of radon-exposure mice. Conclusions: Lung and bronchus might be the targets of radon and its progeny, and p53 gene plays an important role in the progression of radon-induced lung injury. (authors)

A 63-year-old man with peripheral facial nerve paralysis and a pulmonary lesion.

Science.gov (United States)

Yserbyt, J; Wilms, G; Lievens, Y; Nackaerts, K

2009-01-01

Occasionally, malignant neoplasms may cause peripheral facial nerve paralysis as a presenting symptom. A 63-year-old man was referred to the Emergency Department because of a peripheral facial nerve paralysis, lasting for 10 days. Initial diagnostic examinations revealed no apparent cause for this facial nerve paralysis. Chest X-ray, however, showed a suspicious tumoural mass, located in the right hilar region, as confirmed by CAT scan. The diagnosis of an advanced stage lung adenocarcinoma was finally confirmed by bronchial biopsy. MRI scanning showed diffuse brain metastases and revealed a pontine lesion as the most probable underlying cause of this case of peripheral facial nerve paralysis. Platin-based palliative chemotherapy was given, after an initial pancranial irradiation. According to the MRI findings, the pontine lesion was responsible for the peripheral facial nerve paralysis, as an initial presenting symptom in this case of lung adenocarcinoma. This clinical case of a peripheral facial nerve paralysis was caused by a pontine brain metastasis and illustrates a rather rare presenting symptom of metastatic lung cancer.

Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

International Nuclear Information System (INIS)

Rodrigues-Peres, Raquel Mary; Cadore, Solange; Febraio, Stefanny; Heinrich, Juliana Karina; Serra, Katia Piton; Derchain, Sophie F M; Vassallo, Jose; Sarian, Luis Otavio

2013-01-01

Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next logical step is the assessment of whether the aluminum

Accumulation of radium in ferruginous protein bodies formed in lung tissue. Association of resulting radiation hotspots with malignant mesothelioma and other malignancies

International Nuclear Information System (INIS)

Nakamura, Eizo; Makishima, Akio; Hagino, Kyoko; Okabe, Kazunori

2009-01-01

While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers. (author)

Right ventricular systolic pressure measurements in combination with harvest of lung and immune tissue samples in mice.

Science.gov (United States)

Chen, Wen-Chi; Park, Sung-Hyun; Hoffman, Carol; Philip, Cecil; Robinson, Linda; West, James; Grunig, Gabriele

2013-01-16

The function of the right heart is to pump blood through the lungs, thus linking right heart physiology and pulmonary vascular physiology. Inflammation is a common modifier of heart and lung function, by elaborating cellular infiltration, production of cytokines and growth factors, and by initiating remodeling processes. Compared to the left ventricle, the right ventricle is a low-pressure pump that operates in a relatively narrow zone of pressure changes. Increased pulmonary artery pressures are associated with increased pressure in the lung vascular bed and pulmonary hypertension. Pulmonary hypertension is often associated with inflammatory lung diseases, for example chronic obstructive pulmonary disease, or autoimmune diseases. Because pulmonary hypertension confers a bad prognosis for quality of life and life expectancy, much research is directed towards understanding the mechanisms that might be targets for pharmaceutical intervention. The main challenge for the development of effective management tools for pulmonary hypertension remains the complexity of the simultaneous understanding of molecular and cellular changes in the right heart, the lungs and the immune system. Here, we present a procedural workflow for the rapid and precise measurement of pressure changes in the right heart of mice and the simultaneous harvest of samples from heart, lungs and immune tissues. The method is based on the direct catheterization of the right ventricle via the jugular vein in close-chested mice, first developed in the late 1990s as surrogate measure of pressures in the pulmonary artery. The organized team-approach facilitates a very rapid right heart catheterization technique. This makes it possible to perform the measurements in mice that spontaneously breathe room air. The organization of the work-flow in distinct work-areas reduces time delay and opens the possibility to simultaneously perform physiology experiments and harvest immune, heart and lung tissues. The

Detection of SiO2 nanoparticles in lung tissue by ToF-SIMS imaging and fluorescence microscopy.

Science.gov (United States)

Veith, Lothar; Vennemann, Antje; Breitenstein, Daniel; Engelhard, Carsten; Wiemann, Martin; Hagenhoff, Birgit

2017-07-10

The direct detection of nanoparticles in tissues at high spatial resolution is a current goal in nanotoxicology. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is widely used for the direct detection of inorganic and organic substances with high spatial resolution but its capability to detect nanoparticles in tissue sections is still insufficiently explored. To estimate the applicability of this technique for nanotoxicological questions, comparative studies with established techniques on the detection of nanoparticles can offer additional insights. Here, we compare ToF-SIMS imaging data with sub-micrometer spatial resolution to fluorescence microscopy imaging data to explore the usefulness of ToF-SIMS for the detection of nanoparticles in tissues. SiO 2 nanoparticles with a mean diameter of 25 nm, core-labelled with fluorescein isothiocyanate, were intratracheally instilled into rat lungs. Subsequently, imaging of lung cryosections was performed with ToF-SIMS and fluorescence microscopy. Nanoparticles were successfully detected with ToF-SIMS in 3D microanalysis mode based on the lateral distribution of SiO 3 - (m/z 75.96), which was co-localized with the distribution pattern that was obtained from nanoparticle fluorescence. In addition, the lateral distribution of protein (CN - , m/z 26.00) and phosphate based signals (PO 3 - , m/z 78.96) originating from the tissue material could be related to the SiO 3 - lateral distribution. In conclusion, ToF-SIMS is suitable to directly detect and laterally resolve SiO 2 nanomaterials in biological tissue at sufficient intensity levels. At the same time, information about the chemical environment of the nanoparticles in the lung tissue sections is obtained.

FDG uptake in the fatty tissues of supraclavicular and the vascular structure of the lung hilum

International Nuclear Information System (INIS)

Dang Yaping; Liu Gang; Li Miao

2004-01-01

Objectives: To investigate FDG uptake on the sites of supraclavicular region (SR) and the lung hilum (LH) and find out the exact tissues of the uptake. Methods: Supraclavicular region (SR) and lung hilum (LH) are common sites for lymph node metastases. A commonly reported site of non-malignant FDG uptake on PET imaging in the SR is muscular uptake. PET/CT offers a unique technique to correlate PET findings with CT anatomy in the SR and EH. From September 2002 to March 2003, 147 consecutive clinical patients imaged by FDG PET/CT whole-body scan (GE Discovery LS, CT attenuation correction, OSEM reconstruction) were retrospectively reviewed. The presence of abnormal FDG uptake on PET images in the sites of SR and LH regions was evaluated and the corresponding CT findings on the same regions were also assessed. Results: Of 147 patients, 8 cases (2M, 6F and mean age 44 years) were found with increased symmetrical FDG uptake in the regions of the lower neck and shoulder as well as costo-vertebral articulations, the positive rates were 2.1% and 11.3 % for men and women respectively, and the average rate was 5.4%. However, no FDG uptake was seen in the greater muscular structures of the cervical or thoracic spine. FDG uptake was seen in the fatty tissue between the shoulder muscle and the dorsal thoracic wall, but not within the muscles itself. Five patients (3M, 2F, age 56-74 years,3.4%) showed abnormal LH FDG uptake, which were definitely localized in the vascular structure of the lung hilum by CT Conclusion: Co-registered PET/CT imaging shows that the FDG uptake been well known in the SR and LH regions are not fully located in greater muscular structures and lymph nodes, but in the costo-vertebral articulation complex of the thoracic spine and fatty tissue of the shoulders as well as in the vascular structure of both lung hilum. The FDG uptake in the fatty tissue of the shoulders was mostly seen in women, while the uptake in vascular structure of the lung hilum were

Peripheral Tissue Involvement in Sporadic, Iatrogenic, and Variant Creutzfeldt-Jakob Disease

Science.gov (United States)

Head, Mark W.; Ritchie, Diane; Smith, Nadine; McLoughlin, Victoria; Nailon, William; Samad, Sazia; Masson, Stephen; Bishop, Matthew; McCardle, Linda; Ironside, James W.

2004-01-01

Human prion diseases are rare fatal neurodegenerative conditions that occur as acquired, familial, or idiopathic disorders. A key event in their pathogenesis is the accumulation of an altered form of the prion protein, termed PrPSc, in the central nervous system. A novel acquired human prion disease, variant Creutzfeldt-Jakob disease, is thought to result from oral exposure to the bovine spongiform encephalopathy agent. This disease differs from other human prion diseases in its neurological, neuropathological, and biochemical phenotype. We have used immunohistochemistry and Western blot techniques to analyze the tissue distribution and biochemical properties of PrPSc in peripheral tissues in a unique series of nine cases of variant Creutzfeldt-Jakob disease. We have compared this with the distribution and biochemical forms found in all of the major subtypes of sporadic Creutzfeldt-Jakob disease and in a case of iatrogenic Creutzfeldt-Jakob disease associated with growth hormone therapy. The results show that involvement of the lymphoreticular system is a defining feature of variant Creutzfeldt-Jakob disease, but that the biochemical isoform of PrPSc found is influenced by the cell type in which it accumulates. PMID:14695328

Real-time in vivo tissue characterization with diffuse reflectance spectroscopy during transthoracic lung biopsy: a clinical feasibility study

NARCIS (Netherlands)

Spliethoff, Jarich; Prevoo, Warner; Meier, Mark A.J.; de Jong, Jeroen; Evers, Daniel; Evers, Daniel J.; Sterenborg, Hendricus J.C.M.; Lucassen, Gerald; Lucassen, Gerald W.; Hendriks, Benno H.W.; Ruers, Theo J.M.

2016-01-01

Purpose: This study presents the first in vivo real-time tissue characterization during image-guided percutaneous lung biopsies using diffuse reflectance spectroscopy (DRS) sensing at the tip of a biopsy needle with integrated optical fibers. Experimental Design: Tissues from 21 consented patients

CT findings of adenocarcinoma of the lung

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Jeon, T. J.; Kim, S. J.; Lee, D. Y.; Ahn, C. M [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of)

1996-03-01

To evaluate CT findings of primary adenocarcinoma of the lung and to assess distant metastasis at the time of diagnosis. CT findings of 150 patients with adenocarcinoma, confirmed by histopathologic methods, were classified as central or peripheral lesion and pattern analysis of typical findings noted in this cancer was carried out. Intra and extrathoracic metastases of adenocarcinoma were also investigated. Of 150 cases of adenocarcinoma of the lung, 121 were found to be of the peripheral type and 29 were of the central type. These peripheral lesions comprised 105 nodules, 11 consolidations, four cavities and one linear lesion, while the central lesions consisted of 19 cases of atelectasis and tens of branchial wall thickening. lung to lung(nine cases), lymphangitic(five cases), and pleural metastasis(16 cases) were presented as intrathoracic metastasis, while bone(17), brain,(six), liver(two) and adrenal metastasis(one case)were presented as extrathoracic metastasis. The most common radiologic finding of adenocarcinoma is a peripheral single mass or nodule but consolidation, cavity or tubular lesions, as well as atelectasis or bronchial wall thickening alone can be presented as unusual findings of adenocarcinoma. As a consequence, it is in many cases difficult to differentially diagnose. Distant metastasis was also noted in many cases of early T-stage lesion, so to successfully manage the patient, careful evaluation of the metastasis is essential.

CT findings of adenocarcinoma of the lung

International Nuclear Information System (INIS)

Jeon, T. J.; Kim, S. J.; Lee, D. Y.; Ahn, C. M

1996-01-01

To evaluate CT findings of primary adenocarcinoma of the lung and to assess distant metastasis at the time of diagnosis. CT findings of 150 patients with adenocarcinoma, confirmed by histopathologic methods, were classified as central or peripheral lesion and pattern analysis of typical findings noted in this cancer was carried out. Intra and extrathoracic metastases of adenocarcinoma were also investigated. Of 150 cases of adenocarcinoma of the lung, 121 were found to be of the peripheral type and 29 were of the central type. These peripheral lesions comprised 105 nodules, 11 consolidations, four cavities and one linear lesion, while the central lesions consisted of 19 cases of atelectasis and tens of branchial wall thickening. lung to lung(nine cases), lymphangitic(five cases), and pleural metastasis(16 cases) were presented as intrathoracic metastasis, while bone(17), brain,(six), liver(two) and adrenal metastasis(one case)were presented as extrathoracic metastasis. The most common radiologic finding of adenocarcinoma is a peripheral single mass or nodule but consolidation, cavity or tubular lesions, as well as atelectasis or bronchial wall thickening alone can be presented as unusual findings of adenocarcinoma. As a consequence, it is in many cases difficult to differentially diagnose. Distant metastasis was also noted in many cases of early T-stage lesion, so to successfully manage the patient, careful evaluation of the metastasis is essential

Soluble TGF-β type II receptor gene therapy reduces TGF-β activity in irradiated lung tissue and protects lungs from radiation-induced injury

International Nuclear Information System (INIS)

Vujaskovic, Z.; Rabbani, Z.; Zhang, X.; Samulski, T.V.; Li, C.-Y.; Anscher, M.S.

2003-01-01

Full text: The objective was to determine whether administration of recombinant human adenoviral vector carrying soluble TGF-β1 type II receptor (TβR-II) gene reduces availability of active TGFβ1 and protects lung from radiation-induced injury. Female Fisher-344 rats were randomized into four groups to receive: 1) Control 2) Adenoviral green fluorescent protein vector (AdGFP) alone 3) Radiation (RT) + Adenoviral vector with TGF-β1 type II receptor gene (AdexTβR-II-Fc) 4) RT alone. Animals were irradiated to right hemithorax using a single dose of 30 Gy. The packaging and production of a recombinant adenovirus carrying the fused human TβR-II-IgG1 Fc gene was achieved by use of the AdEasy system. The treatment vector AdexTbR-II-Fc (1.5*1010 PFU) and control vector AdGFP (1*109 PFU) were injected i.v. 24 hrs after RT. Respiratory rate was measured as an index of pulmonary function weekly for 5 weeks post RT. Structural damage was scored histologically. Immunohistochemistry was performed to identify activated macrophages. ELISA was used to quantify active TGF-β1 in tissue homogenate. Western blot was used to determine TβR-II expression in plasma and lung tissue. Animals receiving treatment vector AdexTbR-II-Fc have elevated plasma levels of soluble TβR-II at 24 and 48 hours after injection. In the RT+AdexTbR-II-Fc group, there was a significant reduction in respiratory rate (p = 0.002) at four weeks after treatment compared to RT alone group. Histology revealed a significant reduction in lung structural damage in animals receiving gene therapy after RT vs RT alone (p=0.0013). There was also a decrease in the number of activated macrophage (p= 0.02) in RT+AdexTbR-II-Fc group vs RT alone. The tissue protein expression of active TGF-β1 was significantly reduced in rats receiving RT+AdexTbR-II-Fc treatment (p<0.05). This study shows the ability of adenovirus mediated soluble TβR-II gene therapy to reduce tissue levels of active TGF-β1 and ameliorate radiation

Molecular Detection of Neuron-Specific ELAV-Like-Positive Cells in the Peripheral Blood of Patients with Small-Cell Lung Cancer

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Vito D’Alessandro

2008-01-01

Full Text Available Background: n-ELAV (neuronal-Embryonic Lethal, Abnormal Vision-like genes belong to a family codifying for onconeural RNA-binding proteins. Anti-Hu-antibodies (anti-Hu-Ab are typically associated with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/PSN, and low titres of anti-Hu-Ab, were found in newly diagnosed Small Cell Lung Cancer (SCLC. The aim of this study is to develop a sensitive and quantitative molecular real-time PCR assay to detect SCLC cells in peripheral blood (PB through nELAV-like transcripts quantification.

Effect of Lathyrus sativus and vitamin C on the status of aromatic L-amino acid decarboxylase and dipeptidyl-aminopeptidase-IV in the central and peripheral tissues and serum of guinea pigs

International Nuclear Information System (INIS)

Rahman, M.K.; Sarker, M.A.H.

1992-05-01

Studies on the effect of Lathyrus Sativus seeds (LLS) on aromatic L-amino acid decarboxylase (AADC) and on dipeptidyl-aminopeptidase-IV (DAP-IV) were carried out in the central and peripheral tissues and serum of LSS-treated and LSS plus vitamin C-treated guinea pigs. The feeding of LSS for 35 days decreased the AADC activity significantly in the brain and peripheral tissues, but the activity was recovered to normal level in the most tissues when vitamin C was added with the LSS. DAP-IV activity decreased in the peripheral tissues when treated with LSS, but the vitamin C administration with LSS did not recover the enzyme activity. The DAP-IV activity did not decrease significantly in any of the brain tissues of the LSS-treated group. (author). 18 refs, 2 tabs

Peripheral tissue oximetry

DEFF Research Database (Denmark)

Hyttel-Sorensen, Simon; Hessel, Trine Witzner; Greisen, Gorm

2014-01-01

Estimation of regional tissue oxygenation (rStO2) by near infrared spectroscopy enables non-invasive end-organ oxygen balance monitoring and could be a valuable tool in intensive care. However, the diverse absolute values and dynamics of different devices, and overall poor repeatability of measur......Estimation of regional tissue oxygenation (rStO2) by near infrared spectroscopy enables non-invasive end-organ oxygen balance monitoring and could be a valuable tool in intensive care. However, the diverse absolute values and dynamics of different devices, and overall poor repeatability......, and response to changing oxygenation by the down slope of rStO2 during vascular occlusion in the respective arm. 10 healthy adults, 21-29 years old, with double skinfolds on the forearm less than 10 mm participated. The median rStO2 was 70.7% (interquartile range (IQR) 7.7%), 68.4% (IQR 8.4%), and 64.6% (IQR 4...

Characterization of TLR-induced inflammatory responses in COPD and control lung tissue explants

Directory of Open Access Journals (Sweden)

Pomerenke A

2016-09-01

Full Text Available Anna Pomerenke,1 Simon R Lea,1 Sarah Herrick,2 Mark A Lindsay,3 Dave Singh1 1Centre for Respiratory Medicine and Allergy, Institute of Inflammation and Repair, Manchester Academic Health Science Centre, The University of Manchester and University Hospital of South Manchester, NHS Foundation Trust, 2Institute of Inflammation and Repair, Manchester Academic Health Science Centre, University of Manchester, Manchester, 3Department of Pharmacy and Pharmacology, University of Bath, Bath, UK Purpose: Viruses are a common cause of exacerbations in chronic obstructive pulmonary disease (COPD. They activate toll-like receptors (TLRs 3, 7, and 8, leading to a pro-inflammatory response. We have characterized the responses of TLR3 and TLR7/8 in lung tissue explants from COPD patients and control smokers.Methods: We prepared lung whole tissue explants (WTEs from patients undergoing surgery for confirmed or suspected lung cancer. In order to mimic the conditions of viral infection, we used poly(I:C for TLR3 stimulation and R848 for TLR7/8 stimulation. These TLR ligands were used alone and in combination. The effects of tumor necrosis factor α (TNFα neutralization and dexamethasone on TLR responses were examined. Inflammatory cytokine release was measured by enzyme-linked immunosorbent assay and gene expression by quantitative real-time polymerase chain reaction.Results: WTEs from COPD patients released higher levels of pro-inflammatory cytokines compared with WTEs from smokers. Activation of multiple TLRs led to a greater than additive release of TNFα and CCL5. TNFα neutralization and dexamethasone treatment decreased cytokine release.Conclusion: This WTE model shows an enhanced response of COPD compared with controls, suggesting an increased response to viral infection. There was amplification of innate immune responses with multiple TLR stimulation. Keywords: COPD, poly(I:C, R848, cytokines, lung explant

Statistical lung model for microdosimetry

International Nuclear Information System (INIS)

Fisher, D.R.; Hadley, R.T.

1984-03-01

To calculate the microdosimetry of plutonium in the lung, a mathematical description is needed of lung tissue microstructure that defines source-site parameters. Beagle lungs were expanded using a glutaraldehyde fixative at 30 cm water pressure. Tissue specimens, five microns thick, were stained with hematoxylin and eosin then studied using an image analyzer. Measurements were made along horizontal lines through the magnified tissue image. The distribution of air space and tissue chord lengths and locations of epithelial cell nuclei were recorded from about 10,000 line scans. The distribution parameters constituted a model of lung microstructure for predicting the paths of random alpha particle tracks in the lung and the probability of traversing biologically sensitive sites. This lung model may be used in conjunction with established deposition and retention models for determining the microdosimetry in the pulmonary lung for a wide variety of inhaled radioactive materials

Discrimination of prostate cancer from normal peripheral zone and central gland tissue by using dynamic contrast-enhanced MR imaging

NARCIS (Netherlands)

Engelbrecht, Marc R.; Huisman, Henkjan J.; Laheij, Robert J. F.; Jager, Gerrit J.; van Leenders, Geert J. L. H.; Hulsbergen-van de Kaa, Christina A.; de La Rosette, Jean J. M. C. H.; Blickman, Johan G.; Barentsz, Jelle O.

2003-01-01

PURPOSE: To evaluate which parameters of dynamic magnetic resonance (MR) imaging and T2 relaxation rate would result in optimal discrimination of prostatic carcinoma from normal peripheral zone (PZ) and central gland (CG) tissues and to correlate these parameters with tumor stage, Gleason score,

In vivo labelling in several rat tissues of 'peripheral type' benzodiazepine binding sites

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Benavides, J.; Guilloux, F.; Rufat, P.; Uzan, A.; Renault, C.; Dubroeucq, M.C.; Gueremy, C.; Le Fur, G. (Pharmuka Laboratoires, 92 - Gennevilliers (France))

1984-03-16

'Peripheral type' benzodiazepine binding sites in several rat tissues were labelled by intravenous injection of (/sup 3/H)PK 11195 and (/sup 3/H)RO5-4864. Binding was saturable in all tissues studied and regional distribution paralleled the in vitro binding. A similar potency order of displacing compounds was found in vivo and in vitro PK 11195 > PK 11211 > RO5-4864 > diazepam > dipyridamole > clonazepam. These results demonstrate the feasibility of using this technique to examine the effects of pharmacological manipulation on the binding sites in their native state. However, some properties (broader maximum during time course, higher percentage of particulate binding in the brain and independence of temperature) make (/sup 3/H)PK 11195 the most suitable ligand for this kind of studies.

Cavitary Lung Disease in an HIV-Positive Patient

Science.gov (United States)

2009-04-01

alone. Primary lung abscesses are thought to be more common in immunocompromised hosts. The radiographic findings for lung abscess in both...westermani, Entamoeba histolytica, Echinococcus Non Infectious Neoplasm: Primary lung cancer , metastatic carcinoma, lymphoma Pulmonary infarction due to...Congenital (or acquired) bullae, Abscess , Vasculitis, Infection (fungal), TB, and cYst (post-traumatic). A peripheral lung abscesses may also be

Antioxidant effect of sericin in brain and peripheral tissues of oxidative stress induced hypercholesterolemic rats

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Meetali Deori

2016-09-01

Full Text Available This study evaluated the antioxidant effect of crude sericin extract (CSE from Antheraea assamenisis (Aa in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w./day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control (NC, high cholesterol fed (HCF, HCF + 0.065 gm/kg b.w./day fenofibrate (FF, HCF + sericin 0.25 gm/kg b.w./day (LSD and HCF + sericin 0.5 gm/kg b.w./day (HSD. In brain, heart, liver, serum and kidney homogenates nitric oxide (NO, thiobarbituric acid reactive substances (TBARS, protein carbonyl content (PCC, superoxide dismutase (SOD, reduced glutathione (GSH was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress (OS marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies.

TRPA1 channels: expression in non-neuronal murine lung tissues and dispensability for hyperoxia-induced alveolar epithelial hyperplasia.

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Kannler, Martina; Lüling, Robin; Yildirim, Ali Önder; Gudermann, Thomas; Steinritz, Dirk; Dietrich, Alexander

2018-05-12

Transient receptor potential A1 (TRPA1) channels were originally characterized in neuronal tissues but also identified in lung epithelium by staining with fluorescently coupled TRPA1 antibodies. Its exact function in non-neuronal tissues, however, is elusive. TRPA1 is activated in vitro by hypoxia and hyperoxia and is therefore a promising TRP candidate for sensing hyperoxia in pulmonary epithelial cells and for inducing alveolar epithelial hyperplasia. Here, we isolated tracheal, bronchial, and alveolar epithelial cells and show low but detectable TRPA1 mRNA levels in all these cells as well as TRPA1 protein by Western blotting in alveolar type II (AT II) cells. We quantified changes in intracellular Ca 2+ ([Ca 2+ ] i ) levels induced by application of hyperoxic solutions in primary tracheal epithelial, bronchial epithelial, and AT II cells isolated from wild-type (WT) and TRPA1-deficient (TRPA1-/-) mouse lungs. In all cell types, we detected hyperoxia-induced rises in [Ca 2+ ] i levels, which were not significantly different in TRPA1-deficient cells compared to WT cells. We also tested TRPA1 function in a mouse model for hyperoxia-induced alveolar epithelial hyperplasia. A characteristic significant increase in thickening of alveolar tissues was detected in mouse lungs after exposure to hyperoxia, but not in normoxic WT and TRPA1-/- controls. Quantification of changes in lung morphology in hyperoxic WT and TRPA1-/- mice, however, again revealed no significant changes. Therefore, TRPA1 expression does neither appear to be a key player for hyperoxia-induced changes in [Ca 2+ ] i levels in primary lung epithelial cells, nor being essential for the development of hyperoxia-induced alveolar epithelial hyperplasia.

Specific detection of Pasteurella multocida in chickens with fowl cholera and in pig lung tissues using fluorescent rRNA in situ hybridization

DEFF Research Database (Denmark)

Mbuthia, P.G.; Christensen, H.; Boye, Mette

2001-01-01

in formalin-fixed paraffin-embedded lung tissues from experimental fowl cholera in chickens and infections in pigs. In chicken lung tissues P. multocida cells were detected singly, in pairs, as microcolonies, and as massive colonies within air capillaries (septa and lumen), parabronchial septa, and blood...... and fast method for specific detection of P. multocida in histological formalin-fixed tissues. The test was replicable and reproducible and is recommended as a supplementary test for diagnosis and as a tool in pathogenesis studies of fowl cholera and respiratory tract infections in pigs due to P. multocida....

Importance of scatter compensation algorithm in heterogeneous tissue for the radiation dose calculation of small lung nodules. A clinical study

International Nuclear Information System (INIS)

Baba, Yuji; Murakami, Ryuji; Mizukami, Naohisa; Morishita, Shoji; Yamashita, Yasuyuki; Araki, Fujio; Moribe, Nobuyuki; Hirata, Yukinori

2004-01-01

The purpose of this study was to compare radiation doses of small lung nodules calculated with beam scattering compensation and those without compensation in heterogeneous tissues. Computed tomography (CT) data of 34 small (1-2 cm: 12 nodules, 2-3 cm 11 nodules, 3-4 cm 11 nodules) lung nodules were used in the radiation dose measurements. Radiation planning for lung nodule was performed with a commercially available unit using two different radiation dose calculation methods: the superposition method (with scatter compensation in heterogeneous tissues), and the Clarkson method (without scatter compensation in heterogeneous tissues). The energy of the linac photon used in this study was 10 MV and 4 MV. Monitor unit (MU) to deliver 10 Gy at the center of the radiation field (center of the nodule) calculated with the two methods were compared. In 1-2 cm nodules, MU calculated by Clarkson method (MUc) was 90.0±1.1% (4 MV photon) and 80.5±2.7% (10 MV photon) compared to MU calculated by superposion method (MUs), in 2-3 cm nodules, MUc was 92.9±1.1% (4 MV photon) and 86.6±2.8% (10 MV photon) compared to MUs, and in 3-4 cm nodules, MUc was 90.5±2.0% (4 MV photon) and 90.1±1.7% (10 MV photon) compared to MUs. In 1-2 cm nodules, MU calculated without lung compensation (MUn) was 120.6±8.3% (4 MV photon) and 95.1±4.1% (10 MV photon) compared to MU calculated by superposion method (MUs), in 2-3 cm nodules, MUc was 120.3±11.5% (4 MV photon) and 100.5±4.6% (10 MV photon) compared to MUs, and in 3-4 cm nodules, MUc was 105.3±9.0% (4 MV photon) and 103.4±4.9% (10 MV photon) compared to MUs. The MU calculated without lung compensation was not significantly different from the MU calculated by superposition method in 2-3 cm nodules. We found that the conventional dose calculation algorithm without scatter compensation in heterogeneous tissues substantially overestimated the radiation dose of small nodules in the lung field. In the calculation of dose distribution of small

Aluminum concentrations in central and peripheral areas of malignant breast lesions do not differ from those in normal breast tissues

Science.gov (United States)

2013-01-01

Background Aluminum is used in a wide range of applications and is a potential environmental hazard. The known genotoxic effects of aluminum might play a role in the development of breast cancer. However, the data currently available on the subject are not sufficient to establish a causal relationship between aluminum exposure and the augmented risk of developing breast cancer. To achieve maximum sensitivity and specificity in the determination of aluminum levels, we have developed a detection protocol using graphite furnace atomic absorption spectrometry (GFAAS). The objective of the present study was to compare the aluminum levels in the central and peripheral areas of breast carcinomas with those in the adjacent normal breast tissues, and to identify patient and/or tumor characteristics associated with these aluminum levels. Methods A total of 176 patients with breast cancer were included in the study. Samples from the central and peripheral areas of their tumors were obtained, as well as from the surrounding normal breast tissue. Aluminum quantification was performed using GFAAS. Results The average (mean ± SD) aluminum concentrations were as follows: central area, 1.88 ± 3.60 mg/kg; peripheral area, 2.10 ± 5.67 mg/kg; and normal area, 1.68 ± 11.1 mg/kg. Overall and two-by-two comparisons of the aluminum concentrations in these areas indicated no significant differences. We detected a positive relationship between aluminum levels in the peripheral areas of the tumors, age and menopausal status of the patients (P = .02). Conclusions Using a sensitive quantification technique we detected similar aluminum concentrations in the central and peripheral regions of breast tumors, and in normal tissues. In addition, we did not detect significant differences in aluminum concentrations as related to the location of the breast tumor within the breast, or to other relevant tumor features such as stage, size and steroid receptor status. The next

Elevated levels of CXC chemokine connective tissue activating peptide (CTAP)-III in lung cancer patients.

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Lee, Gina; Gardner, Brian K; Elashoff, David A; Purcell, Colleen M; Sandha, Harpavan S; Mao, Jenny T; Krysan, Kostyantyn; Lee, Jay M; Dubinett, Steven M

2011-05-15

Despite advances in treatments, lung cancer has been the leading cause of cancer-related deaths in the United States for the past several decades. Recent findings from the National Lung Screening Trial reveal that low-dose helical computed tomography (CT) scan screening of high-risk individuals reduces lung cancer mortality. This suggests that early detection is of key importance to improving patient outcome. However, of those screened with CT scans, 25% had positive scans that require further follow-up studies which often involve more radiation exposure and invasive tests to reduce false positive results. The purpose of this study was to identify candidate plasma biomarkers to aid in diagnosis of lung cancer in at-risk individuals. We found increased expression of the CXC chemokine connective tissue-activating peptide (CTAP)-III from plasma specimens of lung cancer patients compared to at-risk control subjects. Identification of the peptide was confirmed by the addition of an anti-NAP-2 antibody that recognizes CTAP-III and NAP-2. We also quantified and verified the increased levels of plasma CTAP-III with ELISA in patients with lung cancer (mean ± SD, 1859 ± 1219 ng/mL) compared to controls (698 ± 434 ng/mL; Pcancer patients. Further studies are required to determine if this chemokine could be utilized in a blood-based biomarker panel for the diagnosis of lung cancer.

Tissue and organ regeneration in adults extension of the paradigm to several organs

CERN Document Server

Yannas, Ioannis V

2015-01-01

This textbook describes the basic principles of induced organ regeneration in skin and peripheral nerves and extends the original successful paradigm to other organs. A set of trans-organ rules is established and its use in regeneration of several organs is illustrated from the works of several independent investigators who worked with a variety of organs, such as the lung, the bladder, and the Achilles tendon, using collagen-based scaffolds somewhat similar to the original one. These critical medical treatments fill the clinical need that is not met by organ transplantation. New to this second edition: New information extending the paradigm of tissue regeneration from organ regeneration in skin and peripheral nerves to other organs Guidelines, known as trans-organ rules, are described for the first time for extending this unique medical treatment to organs of several medical specialties The work serves as a comprehensive text and reference for students and practitioners of tissue engineering  

Influence of radiation-dose pattern from inhaled beta--gamma-emitting radionuclides on canine peripheral lymphocytes

International Nuclear Information System (INIS)

Jones, R.K.; Boecker, B.B.; Pickrell, J.A.; Hobbs, C.H.; McClellan, R.O.

1976-01-01

As part of studies assess the biological hazards associated with inhaled radionuclides, periodic hematologic evaluations were performed on beagle dogs given a single nose-only exposure to aerosols of beta--gamma-emitting isotopes. The physical form and specific radionuclides selected produced radiation-dose patterns representative of those which might be encountered in the event of human accidental exposures. Dogs received graded lung burdens of either 90 Y, 91 Y, 144 Ce, or 90 Sr, each in fused clay. Differences in the effective half-lives of these radionuclides resulted in a spectrum of cumulative radiation doses to lung delivered at a variety of dose rates. Since the form in which the radionuclides were inhaled was relatively insoluble, the lung and intrathoracic tissues represented the primary recipient of the dose. Regardless of the effective half-life of radionuclide retention, a dose-related depression of peripheral lymphocytes was observed at various times after inhalation exposure. The time at which maximum depression and subsequent recovery occurred, however, was most directly related to the effective half-life of the radionuclide. Of special interest was the persistence of lymphopenia through 2 1 / 2 years after exposure to 144 Ce and 90 Sr in fused clay where, other than tracheobronchial lymph nodes, the lymphoid tissue received very little radiation dose. The possible mechanisms responsible for lymphocyte depression from these various radiation-dose patterns are discussed

Innate lymphoid cells: the role in respiratory infections and lung tissue damage.

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Głobińska, Anna; Kowalski, Marek L

2017-10-01

Innate lymphoid cells (ILCs) represent a diverse family of cells of the innate immune system, which play an important role in regulation of tissue homeostasis, immunity and inflammation. Emerging evidence has highlighted the importance of ILCs in both protective immunity to respiratory infections and their pathological roles in the lungs. Therefore, the aim of this review is to summarize the current knowledge, interpret and integrate it into broader perspective, enabling greater insight into the role of ILCs in respiratory diseases. Areas covered: In this review we highlighted the role of ILCs in the lungs, citing the most recent studies in this area. PubMed searches (2004- July 2017) were conducted using the term 'innate lymphoid cells respiratory viral infections' in combination with other relevant terms including various respiratory viruses. Expert commentary: Since studies of ILCs have opened new areas of investigation, understanding the role of ILCs in respiratory infections may help to clarify the mechanisms underlying viral-induced exacerbations of lung diseases, providing the basis for novel therapeutic strategies. Potential therapeutic targets have already been identified. So far, the most promising strategy is cytokine-targeting, although further clinical trials are needed to verify its effectiveness.

Localization and stretch-dependence of lung elastase activity in development and compensatory growth.

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Young, Sarah Marie; Liu, Sheng; Joshi, Rashika; Batie, Matthew R; Kofron, Matthew; Guo, Jinbang; Woods, Jason C; Varisco, Brian Michael

2015-04-01

Synthesis and remodeling of the lung matrix is necessary for primary and compensatory lung growth. Because cyclic negative force is applied to developing lung tissue during the respiratory cycle, we hypothesized that stretch is a critical regulator of lung matrix remodeling. By using quantitative image analysis of whole-lung and whole-lobe elastin in situ zymography images, we demonstrated that elastase activity increased twofold during the alveolar stage of postnatal lung morphogenesis in the mouse. Remodeling was restricted to alveolar walls and ducts and was nearly absent in dense elastin band structures. In the mouse pneumonectomy model of compensatory lung growth, elastase activity increased threefold, peaking at 14 days postpneumonectomy and was higher in the accessory lobe compared with other lobes. Remodeling during normal development and during compensatory lung growth was different with increased major airway and pulmonary arterial remodeling during development but not regeneration, and with homogenous remodeling throughout the parenchyma during development, but increased remodeling only in subpleural regions during compensatory lung growth. Left lung wax plombage prevented increased lung elastin during compensatory lung growth. To test whether the adult lung retains an innate capacity to remodel elastin, we developed a confocal microscope-compatible stretching device. In ex vivo adult mouse lung sections, lung elastase activity increased exponentially with strain and in peripheral regions of lung more than in central regions. Our study demonstrates that lung elastase activity is stretch-dependent and supports a model in which externally applied forces influence the composition, structure, and function of the matrix during periods of alveolar septation. Copyright © 2015 the American Physiological Society.

Results of total lung irradiation and chemotherapy in comparison with partial lung irradiation in metastatic undifferentiated soft tissue sarcomas

Energy Technology Data Exchange (ETDEWEB)

Zamboglou, N.; Fuerst, G.; Pape, H.; Bannach, B.; Schmitt, G.; Molls, M.

1988-07-01

The poor prognosis of patients with unresectable pulmonary metastases of soft tissue sarcoma is well known. In order to evaluate the beneficial effect of radiotherapy, we have treated 44 patients with pulmonary metastases of grade 3 soft tissue sarcoma from 1980 to 1986. In 36 patients the treatment volume was restricted to the single metastases up to a dose of 50 to 60 (9 to 10 Gy/week). The survival rate at one year was 18% and at two years 6%. Eight patients were treated with a combined regimen, consisting of cisplatin and ifosfamide with simultaneous whole lung irradiation. Irradiation was performed with 8 or 16 MV photons at a hyperfractionation of 2x0,8 Gy/day (8 Gy/week). After a dose of 12 Gy, the single metastases were boosted up to 50 to 60 Gy, with a second course of chemotherapy. In six of eight patients complete remissions were achieved, one patient showed a partial remission. The survival rate at 27 months was 50%. The patients with partial remission died from pulmonary progression at 23 months. One patient died after twelve months from a loco-regional recurrence in the tonsillar fossa without evidence of pulmonary disease. Side effects included alopecia and moderate bone marrow suppression approximately twelve days after each chemotherapy cycle. Pulmonary fibrosis was observed only at the high dose volume without impairment of respiratory function. From these observations the conclusion is drawn that whole lung irradiation simultaneously with cisplatin and ifosfamide chemotherapy provides good palliative results without relevant morbidity in patients with high grade unresectable pulmonary metastases of soft tissue sarcomas.

Preanalytics in lung cancer.

Science.gov (United States)

Warth, Arne; Muley, Thomas; Meister, Michael; Weichert, Wilko

2015-01-01

Preanalytic sampling techniques and preparation of tissue specimens strongly influence analytical results in lung tissue diagnostics both on the morphological but also on the molecular level. However, in contrast to analytics where tremendous achievements in the last decade have led to a whole new portfolio of test methods, developments in preanalytics have been minimal. This is specifically unfortunate in lung cancer, where usually only small amounts of tissue are at hand and optimization in all processing steps is mandatory in order to increase the diagnostic yield. In the following, we provide a comprehensive overview on some aspects of preanalytics in lung cancer from the method of sampling over tissue processing to its impact on analytical test results. We specifically discuss the role of preanalytics in novel technologies like next-generation sequencing and in the state-of the-art cytology preparations. In addition, we point out specific problems in preanalytics which hamper further developments in the field of lung tissue diagnostics.

Effect of low dose irradiation on subsets of T-lymphocyte of peripheral blood, spleen and tumor tissue

International Nuclear Information System (INIS)

Zou Huawei; Su Liaoyuan; Tian Hailin

1998-01-01

Purpose: In order to understand the mechanism of the stimulation effects of low dose radiation (LDR), the author observed the immune changes of T-lymphocyte subsets. Meteria and methods: Whole body of BALB/C bring-tumor mice were exposed to the doses of 5, 10, 20 and 50 cGy γ-rays. The changes of T-lymphocyte subsets in peripheral blood, spleen and tumor-infiltrating lymphocyte (TIL) were studied with flow cytometry (FCM). Results: the ratio of L 3 T 4 + /Lyt 2 + remarkable increased in the peripheral blood and spleen (p 3 T 4 + /Lyt 2 + further decreased in the TIL group of mice exposed 10 cGy (p 2 + molecules, were concentrated in the tumor tissues and they carried out the killing function to the tumor cells

Lung cancer in connective tissue disease-associated interstitial lung disease: clinical features and impact on outcomes.

Science.gov (United States)

Watanabe, Satoshi; Saeki, Keigo; Waseda, Yuko; Murata, Akari; Takato, Hazuki; Ichikawa, Yukari; Yasui, Masahide; Kimura, Hideharu; Hamaguchi, Yasuhito; Matsushita, Takashi; Yamada, Kazunori; Kawano, Mitsuhiro; Furuichi, Kengo; Wada, Takashi; Kasahara, Kazuo

2018-02-01

Lung cancer (LC) adversely impacts survival in patients with idiopathic pulmonary fibrosis. However, little is known about LC in patients with connective tissue disease-associated interstitial lung disease (CTD-ILD). The aim of this study was to evaluate the prevalence of and risk factors for LC in CTD-ILD, and the clinical characteristics and survival of CTD-ILD patients with LC. We conducted a single-center, retrospective review of patients with CTD-ILD from 2003 to 2016. Patients with pathologically diagnosed LC were identified. The prevalence, risk factors, and clinical features of LC and the impact of LC on CTD-ILD patient outcomes were observed. Of 266 patients with CTD-ILD, 24 (9.0%) had LC. CTD-ILD with LC was more likely in patients who were older, male, and smokers; had rheumatoid arthritis, a usual interstitial pneumonia pattern, emphysema on chest computed tomography scan, and lower diffusing capacity of the lung carbon monoxide (DLco)% predicted; and were not receiving immunosuppressive therapy. Multivariate analysis indicated that the presence of emphysema [odds ratio (OR), 8.473; 95% confidence interval (CI), 2.241-32.033] and nonuse of immunosuppressive therapy (OR, 8.111; 95% CI, 2.457-26.775) were independent risk factors for LC. CTD-ILD patients with LC had significantly worse survival than patients without LC (10-year survival rate: 28.5% vs. 81.8%, P<0.001). LC is associated with the presence of emphysema and nonuse of immunosuppressive therapy, and contributes to increased mortality in patients with CTD-ILD.

Evaluation of peripheral vasodilative indices in skin tissue of type 1 diabetic rats by use of RGB images

Science.gov (United States)

Tanaka, Noriyuki; Nishidate, Izumi; Nakano, Kazuya; Aizu, Yoshihisa; Niizeki, Kyuichi

2016-04-01

We investigated a method to evaluate the arterial inflow and the venous capacitance in the skin tissue of streptozotocin-induced type 1 diabetic rats from RGB digital color images. The arterial inflow and the venous capacitance in the dorsal reversed McFarlane skin flap are calculated based on the responses of change in the total blood concentration to occlusion of blood flow to and from the flap tissues at a pressure of 50 mmHg. The arterial inflow and the venous capacitance in the skin flap tissue were significantly reduced in type 1 diabetic rat group compared with the non-diabetic rat group. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular dysfunctions in diabetes mellitus.

Cross-tissue integration of genetic and epigenetic data offers insight into autism spectrum disorder.

Science.gov (United States)

Andrews, Shan V; Ellis, Shannon E; Bakulski, Kelly M; Sheppard, Brooke; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Feinberg, Andrew P; Arking, Dan E; Ladd-Acosta, Christine; Fallin, M Daniele

2017-10-24

Integration of emerging epigenetic information with autism spectrum disorder (ASD) genetic results may elucidate functional insights not possible via either type of information in isolation. Here we use the genotype and DNA methylation (DNAm) data from cord blood and peripheral blood to identify SNPs associated with DNA methylation (meQTL lists). Additionally, we use publicly available fetal brain and lung meQTL lists to assess enrichment of ASD GWAS results for tissue-specific meQTLs. ASD-associated SNPs are enriched for fetal brain (OR = 3.55; P < 0.001) and peripheral blood meQTLs (OR = 1.58; P < 0.001). The CpG targets of ASD meQTLs across cord, blood, and brain tissues are enriched for immune-related pathways, consistent with other expression and DNAm results in ASD, and reveal pathways not implicated by genetic findings. This joint analysis of genotype and DNAm demonstrates the potential of both brain and blood-based DNAm for insights into ASD and psychiatric phenotypes more broadly.

A 3D human tissue-engineered lung model to study influenza A infection.

Science.gov (United States)

Bhowmick, Rudra; Derakhshan, Mina; Liang, Yurong; Ritchey, Jerry; Liu, Lin; Gappa-Fahlenkamp, Heather

2018-05-05

Influenza A virus (IAV) claims approximately 250,000-500,000 lives annually worldwide. Currently, there are a few in vitro models available to study IAV immunopathology. Monolayer cultures of cell lines and primary lung cells (2D cell culture) is the most commonly used tool, however, this system does not have the in vivo-like structure of the lung and immune responses to IAV as it lacks the three-dimensional (3D) tissue structure. To recapitulate the lung physiology in vitro, a system that contains multiple cell types within a 3D environment that allows cell movement and interaction, would provide a critical tool. In this study, as a first step in designing a 3D-Human Tissue-Engineering Lung Model (3D-HTLM), we described the 3D culture of primary human small airway epithelial cells (HSAEpCs), and determined the immunophenotype of this system in response to IAV infections. We constructed a 3D chitosan-collagen scaffold and cultured HSAEpCs on these scaffolds at air-liquid interface (ALI). These 3D cultures were compared with 2D-cultured HSAEpCs for viability, morphology, marker protein expression, and cell differentiation. Results showed that the 3D-cultured HSAEpCs at ALI yielded maximum viable cells and morphologically resembled the in vivo lower airway epithelium. There were also significant increases in aquaporin-5 and cytokeratin-14 expression for HSAEpCs cultured in 3D compared to 2D. The 3D culture system was used to study the infection of HSAEpCs with two major IAV strains, H1N1 and H3N2.The HSAEpCs showed distinct changes in marker protein expression, both at mRNA and protein levels, and the release of proinflammatory cytokines. This study is the first step in the development of the 3D-HTLM, which will have wide applicability in studying pulmonary pathophysiology and therapeutics development.

FDG uptake in the fatty tissues of supraclavicular and the vascular structure of the lung hilum

International Nuclear Information System (INIS)

Dang Yaping; Liu Gang; Li Miao

2004-01-01

Full text: Supraclavicular region (SR) and lung hilum (LH) are common sites for lymph node metastases. A commonly reported site of non-malignant FDG uptake on PET imaging in the SR is muscular uptake. PET/CT offers a unique technique to correlate PET findings with CT anatomy in the SR and LH. We carried out this study to investigate FDG uptake in SR and LH to find out the exact tissues of FDG uptake. From September 2002 to March 2003, 147 consecutive patients imaged by FDG PET/CT whole-body scan (GE Discovery LS, CT attenuation correction, OSEM reconstruction) were retrospectively reviewed. The presence of abnormal FDG uptake on PET images in SR and LH regions was evaluated and the corresponding CT findings on the same regions were also assessed. Of the 147 patients, 8 cases (2M, 6F and mean age 44 years) were found with increased symmetrical FDG uptake in the regions of the lower neck and shoulder as well as costo-vertebral articulations. The positive rates were 2.1% and 11.3% for men and women respectively, and the average rate was 5.4%. However, no FDG uptake was seen in the greater muscular structures of the cervical or thoracic spine. FDG uptake was seen in the fatty tissue between the shoulder muscle and the dorsal thoracic wall, but not within the muscles itself. Five patients (3M, 2F, age 56-74 years, 3.4%) showed abnormal FDG uptake in LH, which were definitely localized in the vascular structure of the lung hilum by CT. Co-registered PET/CT imaging shows that the FDG uptake, though well known in the SR and LH regions, is not fully located in greater muscular structures and lymph nodes, but in the costo-vertebral articulation complex of the thoracic spine and fatty tissue of the shoulders as well as in the vascular structure of both lung hilum. The FDG uptake in the fatty tissue of the shoulders was mostly seen in women, while the uptake in vascular structure of the lung hilum were found in aged people. (author)

alpha-MSH in systemic inflammation. Central and peripheral actions.

Science.gov (United States)

Catania, A; Delgado, R; Airaghi, L; Cutuli, M; Garofalo, L; Carlin, A; Demitri, M T; Lipton, J M

1999-10-20

Until recently, inflammation was believed to arise from events taking place exclusively in the periphery. However, it is now clear that central neurogenic influences can either enhance or modulate peripheral inflammation. Therefore, it should be possible to improve treatment of inflammation by use of antiinflammatory agents that reduce peripheral host responses and inhibit proinflammatory signals in the central nervous system (CNS). One such strategy could be based on alpha-melanocyte stimulating hormone (alpha-MSH). Increases in circulating TNF-alpha and nitric oxide (NO), induced by intraperitoneal administration of endotoxin in mice, were modulated by central injection of a small concentration of alpha-MSH. Inducible nitric oxide synthase (iNOS) activity and iNOS mRNA in lungs and liver were likewise modulated by central alpha-MSH. Increase in lung myeloperoxidase (MPO) activity was significantly less in lungs of mice treated with central alpha-MSH. Proinflammatory agents induced by endotoxin were significantly greater after blockade of central alpha-MSH. The results suggest that antiinflammatory influences of neural origin that are triggered by alpha-MSH could be used to treat systemic inflammation. In addition to its central influences, alpha-MSH has inhibitory effects on peripheral host cells, in which it reduces release of proinflammatory mediators. alpha-MSH reduces chemotaxis of human neutrophils and production of TNF-alpha, neopterin, and NO by monocytes. In research on septic patients, alpha-MSH inhibited release of TNF-alpha, interleukin-1 beta (IL-1 beta), and interleukin-8 (IL-8) in whole blood samples in vitro. Combined central and peripheral influences can be beneficial in treatment of sepsis.

MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis.

Directory of Open Access Journals (Sweden)

Ivan O Rosas

2008-04-01

Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic progressive fibrotic lung disease associated with substantial morbidity and mortality. The objective of this study was to determine whether there is a peripheral blood protein signature in IPF and whether components of this signature may serve as biomarkers for disease presence and progression.We analyzed the concentrations of 49 proteins in the plasma of 74 patients with IPF and in the plasma of 53 control individuals. We identified a combinatorial signature of five proteins-MMP7, MMP1, MMP8, IGFBP1, and TNFRSF1A-that was sufficient to distinguish patients from controls with a sensitivity of 98.6% (95% confidence interval [CI] 92.7%-100% and specificity of 98.1% (95% CI 89.9%-100%. Increases in MMP1 and MMP7 were also observed in lung tissue and bronchoalveolar lavage fluid obtained from IPF patients. MMP7 and MMP1 plasma concentrations were not increased in patients with chronic obstructive pulmonary disease or sarcoidosis and distinguished IPF compared to subacute/chronic hypersensitivity pneumonitis, a disease that may mimic IPF, with a sensitivity of 96.3% (95% CI 81.0%-100% and specificity of 87.2% (95% CI 72.6%-95.7%. We verified our results in an independent validation cohort composed of patients with IPF, familial pulmonary fibrosis, subclinical interstitial lung disease (ILD, as well as with control individuals. MMP7 and MMP1 concentrations were significantly higher in IPF patients compared to controls in this cohort. Furthermore, MMP7 concentrations were elevated in patients with subclinical ILD and negatively correlated with percent predicted forced vital capacity (FVC% and percent predicted carbon monoxide diffusing capacity (DLCO%.Our experiments provide the first evidence for a peripheral blood protein signature in IPF to our knowledge. The two main components of this signature, MMP7 and MMP1, are overexpressed in the lung microenvironment and distinguish IPF from other chronic lung

SU-E-T-573: Normal Tissue Dose Effect of Prescription Isodose Level Selection in Lung Stereotactic Body Radiation Therapy

International Nuclear Information System (INIS)

Zhang, Q; Lei, Y; Zheng, D; Zhu, X; Wahl, A; Lin, C; Zhou, S; Zhen, W

2015-01-01

Purpose: To evaluate dose fall-off in normal tissue for lung stereotactic body radiation therapy (SBRT) cases planned with different prescription isodose levels (IDLs), by calculating the dose dropping speed (DDS) in normal tissue on plans computed with both Pencil Beam (PB) and Monte-Carlo (MC) algorithms. Methods: The DDS was calculated on 32 plans for 8 lung SBRT patients. For each patient, 4 dynamic conformal arc plans were individually optimized for prescription isodose levels (IDL) ranging from 60% to 90% of the maximum dose with 10% increments to conformally cover the PTV. Eighty non-overlapping rind structures each of 1mm thickness were created layer by layer from each PTV surface. The average dose in each rind was calculated and fitted with a double exponential function (DEF) of the distance from the PTV surface, which models the steep- and moderate-slope portions of the average dose curve in normal tissue. The parameter characterizing the steep portion of the average dose curve in the DEF quantifies the DDS in the immediate normal tissue receiving high dose. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. The DDS were compared among plans with different prescription IDLs, for plans computed with both PB and MC algorithms. Results: For all patients, the DDS was found to be the lowest for 90% prescription IDL and reached a highest plateau region for 60% or 70% prescription. The trend was the same for both PB and MC plans. Conclusion: Among the range of prescription IDLs accepted by lung SBRT RTOG protocols, prescriptions to 60% and 70% IDLs were found to provide best normal tissue sparing

Prognostic significance of tissue polypeptidespecific antigen (TPS) in patients with advanced non-small cell lung cancer

NARCIS (Netherlands)

A. van der Gaast (Ate); C.H.H. Schoenmakers (Christian); T.C. Kok (Tjebbe); B.G. Blijenberg (Bert); W.C.J. Hop (Wim); T.A.W. Splinter (Ted)

1994-01-01

textabstractIn this study, we evaluated the prognostic value of the tumour marker, tissue polypeptide-specific antigen (TPS), in 203 patients with non-small cell lung cancer (NSCLC), and related this to several other known prognostic factors. TPS was significantly correlated with lactate

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

Science.gov (United States)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism.

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Gema Medina-Gomez

2007-04-01

Full Text Available Peroxisome proliferator activated receptor gamma 2 (PPARg2 is the nutritionally regulated isoform of PPARg. Ablation of PPARg2 in the ob/ob background, PPARg2(-/- Lep(ob/Lep(ob (POKO mouse, resulted in decreased fat mass, severe insulin resistance, beta-cell failure, and dyslipidaemia. Our results indicate that the PPARg2 isoform plays an important role, mediating adipose tissue expansion in response to positive energy balance. Lipidomic analyses suggest that PPARg2 plays an important antilipotoxic role when induced ectopically in liver and muscle by facilitating deposition of fat as relatively harmless triacylglycerol species and thus preventing accumulation of reactive lipid species. Our data also indicate that PPARg2 may be required for the beta-cell hypertrophic adaptive response to insulin resistance. In summary, the PPARg2 isoform prevents lipotoxicity by (a promoting adipose tissue expansion, (b increasing the lipid-buffering capacity of peripheral organs, and (c facilitating the adaptive proliferative response of beta-cells to insulin resistance.

Killing effect of EGFR-TKI combined with 125I seed implantation therapy on ⅢB-Ⅳ stage lung cancer tissue

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Ai-Sheng Xiang

2016-12-01

Full Text Available Objective: To analyze the killing effect of EGFR-TKI combined with 125I seed implantation therapy on ⅢB-Ⅳ stage lung cancer tissue. Methods: A total of 78 patients with ⅢB-Ⅳ stage lung cancer were randomly divided into observation group and control group (n=39, control group received EGFR-TKI treatment and observation group received EGFR-TKI combined with 125I seed implantation therapy. Differences in apoptosis gene, invasion gene and autophagy gene expression in lung tissue were compared between two groups after 1 month of treatment. Results: Apoptosis genes PDCD5, bax and bcl-xS mRNA expression levels in lung tissue of observation group after 1 month of treatment were higher than those of control group while Bag-1, survivin and bcl-xL mRNA expression levels were lower than those of control group; invasion genes CD147, EGFR and DDX17 mRNA expression levels were lower than those of control group while Bin1, E-cadherin and Ovol2 mRNA expression levels were higher than those of control group; autophagy genes ARHI, Beclin1, Atg5, LC3B, pULK and PI3KC3 mRNA expression levels were higher than those of control group. Conclusions: EGFR-TKI combined with 125I seed implantation therapy can enhance the tumor killing effect on patients with ⅢB-Ⅳ stage lung cancer, and contribute to the optimization of overall condition and the extension of survival time.

Lung cancer screening beyond low-dose computed tomography: the role of novel biomarkers.

Science.gov (United States)

Hasan, Naveed; Kumar, Rohit; Kavuru, Mani S

2014-10-01

Lung cancer is the most common and lethal malignancy in the world. The landmark National lung screening trial (NLST) showed a 20% relative reduction in mortality in high-risk individuals with screening low-dose computed tomography. However, the poor specificity and low prevalence of lung cancer in the NLST provide major limitations to its widespread use. Furthermore, a lung nodule on CT scan requires a nuanced and individualized approach towards management. In this regard, advances in high through-put technology (molecular diagnostics, multi-gene chips, proteomics, and bronchoscopic techniques) have led to discovery of lung cancer biomarkers that have shown potential to complement the current screening standards. Early detection of lung cancer can be achieved by analysis of biomarkers from tissue samples within the respiratory tract such as sputum, saliva, nasal/bronchial airway epithelial cells and exhaled breath condensate or through peripheral biofluids such as blood, serum and urine. Autofluorescence bronchoscopy has been employed in research setting to identify pre-invasive lesions not identified on CT scan. Although these modalities are not yet commercially available in clinic setting, they will be available in the near future and clinicians who care for patients with lung cancer should be aware. In this review, we present up-to-date state of biomarker development, discuss their clinical relevance and predict their future role in lung cancer management.

Computer program modifications for lung microdosimetry

International Nuclear Information System (INIS)

Harty, R.; Hadley, R.T.

1983-01-01

A lung model based on statistical studies of beagle dog lung microstructure was incorporated to describe the distributions of tissue, air space, and cell nuclei in pulmonary lung tissue was modified from basic to FORTRAN to shorten time and increase flexibility

Microsecond-pulsed dielectric barrier discharge plasma stimulation of tissue macrophages for treatment of peripheral vascular disease

Energy Technology Data Exchange (ETDEWEB)

Miller, V., E-mail: vmiller@coe.drexel.edu; Lin, A.; Brettschneider, J.; Fridman, G.; Fridman, A. [AJ Drexel Plasma Institute, Drexel University, Camden, New Jersey 08103 (United States); Kako, F.; Gabunia, K.; Kelemen, S.; Autieri, M. [Department of Physiology, Independence Blue Cross Cardiovascular Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140 (United States)

2015-12-15

Angiogenesis is the formation of new blood vessels from pre-existing vessels and normally occurs during the process of inflammatory reactions, wound healing, tissue repair, and restoration of blood flow after injury or insult. Stimulation of angiogenesis is a promising and an important step in the treatment of peripheral artery disease. Reactive oxygen species have been shown to be involved in stimulation of this process. For this reason, we have developed and validated a non-equilibrium atmospheric temperature and pressure short-pulsed dielectric barrier discharge plasma system, which can non-destructively generate reactive oxygen species and other active species at the surface of the tissue being treated. We show that this plasma treatment stimulates the production of vascular endothelial growth factor, matrix metalloproteinase-9, and CXCL 1 that in turn induces angiogenesis in mouse aortic rings in vitro. This effect may be mediated by the direct effect of plasma generated reactive oxygen species on tissue.

Dosimetric lung models

International Nuclear Information System (INIS)

James, A.C.; Roy, M.

1986-01-01

The anatomical and physiological factors that vary with age and influence the deposition of airborne radionuclides in the lung are reviewed. The efficiency with which aerosols deposit in the lung for a given exposure at various ages from birth to adulthood is evaluated. Deposition within the lung is considered in relation to the clearance mechanisms acting in different regions or compartments. The procedure for evaluating dose to sensitive tissues in lung and transfer to other organs that is being considered by the Task Group established by ICRP to review the Lung Model is outlined. Examples of the application of this modelling procedure to evaluate lung dose as a function of age are given, for exposure to radon daughters in dwellings, and for exposure to an insoluble 239 Pu aerosol. The former represents exposure to short-lived radionuclides that deliver relatively high doses to bronchial tissue. In this case, dose rates are marginally higher in children than in adults. Plutonium exposure represents the case where dose is predominantly delivered to respiratory tissue and lymph nodes. In this case, the life-time doses tend to be lower for exposure in childhood. Some of the uncertainties in this modelling procedure are noted

Peripheral and central localization of the nesfatin-1 receptor using autoradiography in rats

Energy Technology Data Exchange (ETDEWEB)

Prinz, Philip [Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin (Germany); Goebel-Stengel, Miriam [Department of Internal Medicine, Martin-Luther Krankenhaus, Caspar-Theyß-Str. 27-31, 14193 Berlin (Germany); Teuffel, Pauline; Rose, Matthias; Klapp, Burghard F. [Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin (Germany); Stengel, Andreas, E-mail: andreas.stengel@charite.de [Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12203 Berlin (Germany)

2016-02-12

Nesfatin-1 was recently identified and introduced as food intake-regulatory hormone. Soon thereafter, mounting evidence indicated a much broader role for nesfatin-1 with an involvement in the regulation of food intake, gastrointestinal motility, glucose homeostasis, blood pressure and stress. Despite the growing knowledge on the physiological regulation and functions of nesfatin-1, the receptor mediating these effects remains to be characterized. Therefore, the aim of this study was to investigate the peripheral and central localization of the nesfatin-1 receptor by autoradiography. Male Sprague–Dawley rats were used and peripheral as well as brain tissue was processed for {sup 125}I-nesfatin-1 autoradiography. In peripheral tissues, an autoradiographic signal was observed in the gastric mucosa of corpus and antrum, in duodenum, jejunum and ileum, while no signal was detected in the colon. Preabsorption of {sup 125}I-nesfatin-1 with non-labeled nesfatin-1 greatly diminished the autoradiographic signal in the stomach indicating specificity (−32%, p < 0.001). A displacement assay showed an effective concentration by which 50% of {sup 125}I-nesfatin-1 bound to the receptor (EC{sub 50}) in the gastric corpus of 80 pM. Moreover, autoradiography was observed in endocrine tissues including the pituitary, pancreas, adrenal gland, testis and visceral adipose tissue. In addition, also heart, skeletal muscle, lung, liver and kidney showed autoradiographic signals. In the brain, strong {sup 125}I-nesfatin-1 autoradiography was detected in the cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum. Based on the distribution of nesfatin-1 autoradiography, nesfatin-1 is a pleiotropic hormone that is involved in the regulation of several homeostatic functions. - Highlights: • Although our knowledge on nesfatin-1 is increasing, the receptor is still unknown. • {sup 125}I-nesfatin-1 autoradiography was

Early resuscitation with polymerized bovine hemoglobin reverses acidosis, but not peripheral tissue oxygenation, in a severe hamster shock model.

Science.gov (United States)

Wettstein, Reto; Tsai, Amy G; Harder, Yves; Erni, Dominique; Intaglietta, Marcos

2006-11-01

Awake hamsters equipped with the dorsal window chamber preparation were subjected to hemorrhage of 50% of the estimated blood volume. Initial resuscitation (25% of estimated blood volume) with polymerized bovine hemoglobin (PBH) or 10% hydroxyethyl starch (HES) occurred in concert with an equivolumetric bleeding to simulate the early, prehospital setting (exchange transfusion). Resuscitation (25% of estimated blood volume) without bleeding was performed with PBH, HES, or autologous red blood cells (HES-RBCs). Peripheral microcirculation, tissue oxygenation, and systemic hemodynamic and blood gas parameters were assessed. After exchange transfusion, base deficit was -8.6 +/- 3.7 mmol/L (PBH) and -5.1 +/- 5.3 mmol/L (HES) (not significant). Functional capillary density was 17% +/- 6% of baseline (PBH) and 31% +/- 11% (HES) (P < 0.05) and arteriolar diameter 73% +/- 3% of baseline (PBH) and 90% + 5% (HES) (P < 0.01). At the end, hemoglobin levels were 3.7 +/- 0.3 g/dL with HES, 8.2 +/- 0.6 g/dL with PBH, and 10.4 +/- 0.8 g/dL with HES-RBCs (P < 0.01 HES vs. PBH and HES-RBCs, P < 0.05 PBH vs. HES-RBCs). Base excess was restored to baseline with PBH and HES-RBCs, but not with HES (P < 0.05). Functional capillary density was 46% +/- 5% of baseline (PBH), 62% + 20% (HES-RBCs), and 36% +/- 19% (HES) (P < 0.01 HES-RBCs vs. HES). Peripheral oxygen delivery and consumption was highest with HES-RBCs, followed by PBH (P < 0.05 HES-RBCs vs. PBH, P < 0.01 HES-RBCs and PBH vs. HES). In conclusion, the PBH led to a correction of base deficit comparable to blood transfusion. However, oxygenation of the peripheral tissue was inferior with PBH. This was attributed to its negative impact on the peripheral microcirculation caused by arteriolar vasoconstriction.

Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT polymorphism in a prospective cohort study among women in China.

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Qing Lan

Full Text Available A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR, 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003. Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030. Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.

[Elevated expression of endothelin 2 in lung tissues of asthmatic rats after exposed to cigarette smoke and its mechanism].

Science.gov (United States)

Han, Fangfang; Zhu, Shuyang; Chen, Bi; Li, Jingjing

2017-08-01

Objective To study the effect of cigarette smoke exposure on the expression of endothelin 2 (ET-2) in bronchial epithelium of asthmatic rats. Methods Asthma models were established through intraperitoneal injection of 1 mL chicken ovalbumin (OVA)/Al(OH) 3 mixture (asthma model group, n=6); based on the asthma models, exposure to smoking gas lasted four weeks with 10 cigarettes per day (smoke-exposed asthma group, n=6); based on the smoke-exposed asthma models, the rats were treated with intraperitoneal injection of dexamethasone 2 mg/(kg.d), intragastric administration of ET receptor inhibitor bosentan 100 mg/(kg.d) and combined use, respectively named dexamethasone treated group, bosentan treated group, and dexamethasone-bosentan treated group, 6 rats in every group. What's more, other 6 rats were only subjected to intraperitoneal injection of 1 mL normal saline as normal controls; in addition to the injection of saline, cigarette smoke control group (n=6) was set up by the exposure to smoking gas for four weeks with 10 cigarettes per day. Bronchoalveolar lavage fluid (BALF) was collected from the upper lobe of the left lung for cell counting and classification. Pathological changes of the right upper lung lobe tissues were observed by HE staining. In other lung tissues, the expression of JNK1/2 was detected by Western blotting; ET-2 was tested by Western blotting and immunohistochemistry; thiobarbituric acid reactive substances (TBARS) assay and trace enzyme standard method were used to measure malondialdehyde (MDA) and glutathione (GSH), respectively. Results Compared with normal control group, the number of airway inflammation cells increased in the BALF, and the expressions of ET-2, JNK1/2, MDA and GSH increased in the lung tissues of cigarette smoke control group, asthma model group and cigarette smoke-exposed asthma group. Compared with cigarette smoke-exposed asthma group, the number of airway inflammation cells decreased in the BALF, and the expressions of

Effect of chest wall radiotherapy in different manners using tissue equivalent bolus on skin and lung of cavia cobayas

International Nuclear Information System (INIS)

Huang Wei; Qu Yaqin; Song Xiangfu; Liu Shixin; Jia Xiaojing; Guo He; Yang Lei

2009-01-01

Objective: To probe the influence of electron beam radiotherapy in different manners using different tissue equivalent boluses on skin and lung. Methods: Adult female cavia cobayas were randomly divided into four groups as control group, half-time with bolus group, half-time with bolus group and without bolus group. Acute-irradiation animal models were established using electron beam in different manners with or without 0.5 cm tissue equivalent bolus. Pathological changes in lung, hair vesicle and fibroblast cell count were analyzed 40 clays after irradiation. Results: The radiation dermatitis in the group with bolus was slighter than that of the group without bolus, but the radiation pneumonia was reverse. With bolus, the radiation dermatitis of haft-time group was slighter than that of full-time group. The injury repair of half-time group was more active than full-time group. Conclusions: The treatment of haft-time bolus could protect lung without serious skin complications. (authors)

Imaging of a glioma using peripheral benzodiazepine receptor ligands

Energy Technology Data Exchange (ETDEWEB)

Starosta-Rubinstein, S.; Ciliax, B.J.; Penney, J.B.; McKeever, P.; Young, A.B.

1987-02-01

Two types of benzodiazepine receptors have been demonstrated in mammalian tissues, one which is localized on neuronal elements in brain and the other, on glial cells and in peripheral tissues such as kidney. In vivo administration of /sup 3/H-labeled PK 11195 (1-(2-chlorophenyl-N-methyl-N-(1-methylpropyl)-3-isoquinoline carboxamide) or (/sup 3/H)flunitrazepam with 5 mg of clonazepam per kg to rats with intracranial C6 gliomas resulted in high levels of tritiated-drug binding to the tumor as shown by quantitative autoradiography. Pharmacological studies indicated that the bound drugs labeled the peripheral benzodiazepine binding site. Binding to the peripheral benzodiazepine site was confirmed primarily to malignant cells with little binding to adjacent normal brain tissue or to necrotic tissue. Tumor cell binding was completely inhibited by preadministration of the peripheral benzodiazepine blocking agent PK 11195 at 5 mg/kg. The centrally selective benzodiazepine ligand clonazepam had no effect on PK 11195 binding to the tumor cells. When binding to other tumor cell lines grown in nude mice and nude athymic rats was evaluated, little or no peripheral benzodiazepine binding was detected on human pheochromocytoma (RN1) and neuroblastoma (SK-N-MC, SK-N-SH) tumor cells, respectively. However, high densities of peripheral benzodiazepine binding sites were observed on tumors derived from a human glioma cell line (ATCC HTB 14, U-87 MG). The presence of high concentrations of specific peripheral benzodiazepine receptors on glial tumors suggests that human primary central nervous system tumors could be imaged and diagnosed using peripheral benzodiazepine ligands labeled with positron- or gamma-emitting isotopes.

Immunohistochemical Analysis in the Rat Central Nervous System and Peripheral Lymph Node Tissue Sections.

Science.gov (United States)

Adzemovic, Milena Z; Zeitelhofer, Manuel; Leisser, Marianne; Köck, Ulricke; Kury, Angela; Olsson, Tomas

2016-11-14

Immunohistochemistry (IHC) provides highly specific, reliable and attractive protein visualization. Correct performance and interpretation of an IHC-based multicolor labeling is challenging, especially when utilized for assessing interrelations between target proteins in the tissue with a high fat content such as the central nervous system (CNS). Our protocol represents a refinement of the standard immunolabeling technique particularly adjusted for detection of both structural and soluble proteins in the rat CNS and peripheral lymph nodes (LN) affected by neuroinflammation. Nonetheless, with or without further modifications, our protocol could likely be used for detection of other related protein targets, even in other organs and species than here presented.

Lung cancer in uranium miners: A tissue resource and pilot study. Final performance report

International Nuclear Information System (INIS)

Samet, J.; Gilliland, F.D.

1998-01-01

This project incorporates two related research projects directed toward understanding respiratory carcinogenesis in radon-exposed former uranium miners. The first project involved a continuation of the tissue resource of lung cancer cases from former underground uranium miners and comparison cases from non-miners. The second project was a pilot study for a proposed longitudinal study of respiratory carcinogenesis in former uranium miners. The objectives including facilitating the investigation of molecular changes in radon exposed lung cancer cases, developing methods for prospectively studying clinical, cytologic, cytogenetic, and molecular changes in the multi-event process of respiratory carcinogenesis, and assessing the feasibility of recruiting former uranium miners into a longitudinal study that collected multiple biological specimens. A pilot study was conducted to determine whether blood collection, induced sputum, bronchial brushing, washings, and mucosal biopsies from participants at two of the hospitals could be included efficiently. A questionnaire was developed for the extended study and all protocols for specimen collection and tissue handling were completed. Resource utilization is in progress at ITRI and the methods have been developed to study molecular and cellular changes in exfoliated cells contained in sputum as well as susceptibility factors

Lung cancer in uranium miners: A tissue resource and pilot study. Final performance report

Energy Technology Data Exchange (ETDEWEB)

Samet, J.; Gilliland, F.D.

1998-08-13

This project incorporates two related research projects directed toward understanding respiratory carcinogenesis in radon-exposed former uranium miners. The first project involved a continuation of the tissue resource of lung cancer cases from former underground uranium miners and comparison cases from non-miners. The second project was a pilot study for a proposed longitudinal study of respiratory carcinogenesis in former uranium miners. The objectives including facilitating the investigation of molecular changes in radon exposed lung cancer cases, developing methods for prospectively studying clinical, cytologic, cytogenetic, and molecular changes in the multi-event process of respiratory carcinogenesis, and assessing the feasibility of recruiting former uranium miners into a longitudinal study that collected multiple biological specimens. A pilot study was conducted to determine whether blood collection, induced sputum, bronchial brushing, washings, and mucosal biopsies from participants at two of the hospitals could be included efficiently. A questionnaire was developed for the extended study and all protocols for specimen collection and tissue handling were completed. Resource utilization is in progress at ITRI and the methods have been developed to study molecular and cellular changes in exfoliated cells contained in sputum as well as susceptibility factors.

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study.

Science.gov (United States)

Torino, Claudia; Gargani, Luna; Sicari, Rosa; Letachowicz, Krzysztof; Ekart, Robert; Fliser, Danilo; Covic, Adrian; Siamopoulos, Kostas; Stavroulopoulos, Aristeidis; Massy, Ziad A; Fiaccadori, Enrico; Caiazza, Alberto; Bachelet, Thomas; Slotki, Itzchak; Martinez-Castelao, Alberto; Coudert-Krier, Marie-Jeanne; Rossignol, Patrick; Gueler, Faikah; Hannedouche, Thierry; Panichi, Vincenzo; Wiecek, Andrzej; Pontoriero, Giuseppe; Sarafidis, Pantelis; Klinger, Marian; Hojs, Radovan; Seiler-Mussler, Sarah; Lizzi, Fabio; Siriopol, Dimitrie; Balafa, Olga; Shavit, Linda; Tripepi, Rocco; Mallamaci, Francesca; Tripepi, Giovanni; Picano, Eugenio; London, Gérard Michel; Zoccali, Carmine

2016-11-07

Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ-statistics (κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at

Promoting peripheral myelin repair.

Science.gov (United States)

Zhou, Ye; Notterpek, Lucia

2016-09-01

Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the target of myelin repair strategies in acute injuries and chronic diseases, such as hereditary demyelinating neuropathies. In one approach, the endogenous regenerative capacity of Schwann cells is enhanced through interventions such as exercise, electrical stimulation or pharmacological means. Alternatively, Schwann cells derived from healthy nerves, or engineered from different tissue sources have been transplanted into the PNS to support remyelination. These transplant approaches can then be further enhanced by exercise and/or electrical stimulation, as well as by the inclusion of biomaterial engineered to support glial cell viability and neurite extension. Advances in our basic understanding of peripheral nerve biology, as well as biomaterial engineering, will further improve the functional repair of myelinated peripheral nerves. Copyright © 2016 Elsevier Inc. All rights reserved.

Histone deacetylase 2 is decreased in peripheral blood pro-inflammatory CD8+ T and NKT-like lymphocytes following lung transplant.

Science.gov (United States)

Hodge, Greg; Hodge, Sandra; Holmes-Liew, Chien-Li; Reynolds, Paul N; Holmes, Mark

2017-02-01

Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown. We hypothesized decreased HDAC2 expression and increased HAT expression in pro-inflammatory lymphocytes following lung transplant. Blood was collected from 18 stable lung transplant patients and 10 healthy age-matched controls. Intracellular pro-inflammatory cytokines and HAT/HDAC2 expression were determined in lymphocyte subsets following culture using flow cytometry. A loss of HDAC2 in cluster of differentiation (CD) 8+ T and NKT-like cells in transplant patients compared with controls was noted (CD8+ T: 28 ± 10 (45 ± 10), CD8+NKT-like: 30 ± 13 (54 ± 16) (mean ± SD transplant) (control)). Loss of HDAC2 was associated with an increased percentage of CD8+ T and NKT-like cells expressing perforin, granzyme b, interferon gamma (IFN-γ) and TNF-α (no change in HAT expression in any lymphocyte subset). There was a negative correlation between loss of HDAC2 expression by CD8+ T cells with cumulative dose of prednisolone and time post-transplant. Treatment with 10 mg/L theophylline + 1 µmol/L prednisolone or 2.5 ng/mL cyclosporine A synergistically upregulated HDAC2 and inhibited IFN-γ and TNF-α production by CD8+ T and NKT-like lymphocytes. HDAC2 is decreased in CD8+ T and NKT-like pro-inflammatory lymphocytes following lung transplant. Treatment options that increase HDAC2 may improve graft survival. © 2016 Asian Pacific Society of Respirology.

KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only.

Directory of Open Access Journals (Sweden)

Yuki Togashi

Full Text Available The promising results of anaplastic lymphoma kinase (ALK inhibitors have changed the significance of ALK fusions in several types of cancer. These fusions are no longer mere research targets or diagnostic markers, but they are now directly linked to the therapeutic benefit of patients. However, most available tumor tissues in clinical settings are formalin-fixed and paraffin-embedded (FFPE, and this significantly limits detailed genetic studies in many clinical cases. Although recent technical improvements have allowed the analysis of some known mutations in FFPE tissues, identifying unknown fusion genes by using only FFPE tissues remains difficult. We developed a 5'-rapid amplification of cDNA ends-based system optimized for FFPE tissues and evaluated this system on a lung cancer tissue with ALK rearrangement and without the 2 known ALK fusions EML4-ALK and KIF5B-ALK. With this system, we successfully identified a novel ALK fusion, KLC1-ALK. The result was confirmed by reverse transcription-polymerase chain reaction and fluorescence in situ hybridization. Then, we synthesized the putative full-length cDNA of KLC1-ALK and demonstrated the transforming potential of the fusion kinase with assays using mouse 3T3 cells. To the best of our knowledge, KLC1-ALK is the first novel oncogenic fusion identified using only FFPE tissues. This finding will broaden the potential value of archival FFPE tissues and provide further biological and clinical insights into ALK-positive lung cancer.

Dynamic culture of a thermosensitive collagen hydrogel as an extracellular matrix improves the construction of tissue-engineered peripheral nerve.

Science.gov (United States)

Huang, Lanfeng; Li, Rui; Liu, Wanguo; Dai, Jin; Du, Zhenwu; Wang, Xiaonan; Ma, Jianchao; Zhao, Jinsong

2014-07-15

Tissue engineering technologies offer new treatment strategies for the repair of peripheral nerve injury, but cell loss between seeding and adhesion to the scaffold remains inevitable. A thermosensitive collagen hydrogel was used as an extracellular matrix in this study and combined with bone marrow mesenchymal stem cells to construct tissue-engineered peripheral nerve composites in vitro. Dynamic culture was performed at an oscillating frequency of 0.5 Hz and 35° swing angle above and below the horizontal plane. The results demonstrated that bone marrow mesenchymal stem cells formed membrane-like structures around the poly-L-lactic acid scaffolds and exhibited regular alignment on the composite surface. Collagen was used to fill in the pores, and seeded cells adhered onto the poly-L-lactic acid fibers. The DNA content of the bone marrow mesenchymal stem cells was higher in the composites constructed with a thermosensitive collagen hydrogel compared with that in collagen I scaffold controls. The cellular DNA content was also higher in the thermosensitive collagen hydrogel composites constructed with the thermosensitive collagen hydrogel in dynamic culture than that in static culture. These results indicate that tissue-engineered composites formed with thermosensitive collagen hydrogel in dynamic culture can maintain larger numbers of seeded cells by avoiding cell loss during the initial adhesion stage. Moreover, seeded cells were distributed throughout the material.

Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer

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Martin, Kate L.; Gomez, Jorge; Nazareth, Daryl P.; Warren, Graham W. [Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, NY (United States); Singh, Anurag K., E-mail: anurag.singh@roswellpark.org [Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, NY (United States)

2012-07-01

To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectively for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.

Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non–small cell lung cancer

International Nuclear Information System (INIS)

Martin, Kate L.; Gomez, Jorge; Nazareth, Daryl P.; Warren, Graham W.; Singh, Anurag K.

2012-01-01

To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non–small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectively for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.

Mechanical phenotyping of cells and extracellular matrix as grade and stage markers of lung tumor tissues.

Science.gov (United States)

Panzetta, Valeria; Musella, Ida; Rapa, Ida; Volante, Marco; Netti, Paolo A; Fusco, Sabato

2017-07-15

The mechanical cross-talk between cells and the extra-cellular matrix (ECM) regulates the properties, functions and healthiness of the tissues. When this is disturbed it changes the mechanical state of the tissue components, singularly or together, and cancer, along with other diseases, may start and progress. However, the bi-univocal mechanical interplay between cells and the ECM is still not properly understood. In this study we show how a microrheology technique gives us the opportunity to evaluate the mechanics of cells and the ECM at the same time. The mechanical phenotyping was performed on the surgically removed tissues of 10 patients affected by adenocarcinoma of the lung. A correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Our findings suggest a sort of asymmetric modification of the mechanical properties of the cells and the extra-cellular matrix in the tumor, being the more compliant cell even though it resides in a stiffer matrix. Overall, the simultaneous mechanical characterization of the tissues constituents (cells and ECM) provided new support for diagnosis and offered alternative points of analysis for cancer mechanobiology. When the integrity of the mechanical cross-talk between cells and the extra-cellular matrix is disturbed cancer, along with other diseases, may initiate and progress. Here, we show how a new technique gives the opportunity to evaluate the mechanics of cells and the ECM at the same time. It was applied on surgically removed tissues of 10 patients affected by adenocarcinoma of the lung and a correlation between the mechanics and the grade and stage of the tumor was reported and compared to the mechanical characteristics of the healthy tissue. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Induction of mesenchymal cell phenotypes in lung epithelial cells by adenovirus E1A.

Science.gov (United States)

Behzad, A R; Morimoto, K; Gosselink, J; Green, J; Hogg, J C; Hayashi, S

2006-12-01

Epithelial-mesenchymal transformation is now recognised as an important feature of tissue remodelling. The present report concerns the role of adenovirus infection in inducing this transformation in an animal model of chronic obstructive pulmonary disease. Guinea pig primary peripheral lung epithelial cells (PLECs) transfected with adenovirus E1A (E1A-PLECs) were compared to guinea pig normal lung fibroblasts (NLFs) transfected with E1A (E1A-NLFs). These cells were characterised by PCR, immunocytochemistry, electron microscopy, and Western and Northern blot analyses. Electrophoretic mobility shift assays were performed in order to examine nuclear factor (NF)-kappaB and activator protein (AP)-1 binding activities. E1A-PLECs and E1A-NLFs positive for E1A DNA, mRNA and protein expressed cytokeratin and vimentin but not smooth muscle alpha-actin. Both exhibited cuboidal morphology and junctional complexes, but did not contain lamellar bodies or express surfactant protein A, B or C mRNAs. These two cell types differed, however, in their NF-kappaB and AP-1 binding after lipopolysaccharide stimulation, possibly due to differences in the expression of the subunits that comprise these transcriptional complexes. E1A transfection results in the transformation of peripheral lung epithelial cells and normal lung fibroblasts to a phenotype intermediate between that of the two primary cells. It is postulated that this intermediate phenotype may play a major role in the remodelling of the airways in chronic obstructive pulmonary disease associated with persistence of adenovirus E1A DNA.

Mesenchymal Stem Cells Adopt Lung Cell Phenotype in Normal and Radiation-induced Lung Injury Conditions.

Science.gov (United States)

Maria, Ola M; Maria, Ahmed M; Ybarra, Norma; Jeyaseelan, Krishinima; Lee, Sangkyu; Perez, Jessica; Shalaby, Mostafa Y; Lehnert, Shirley; Faria, Sergio; Serban, Monica; Seuntjens, Jan; El Naqa, Issam

2016-04-01

Lung tissue exposure to ionizing irradiation can invariably occur during the treatment of a variety of cancers leading to increased risk of radiation-induced lung disease (RILD). Mesenchymal stem cells (MSCs) possess the potential to differentiate into epithelial cells. However, cell culture methods of primary type II pneumocytes are slow and cannot provide a sufficient number of cells to regenerate damaged lungs. Moreover, effects of ablative radiation doses on the ability of MSCs to differentiate in vitro into lung cells have not been investigated yet. Therefore, an in vitro coculture system was used, where MSCs were physically separated from dissociated lung tissue obtained from either healthy or high ablative doses of 16 or 20 Gy whole thorax irradiated rats. Around 10±5% and 20±3% of cocultured MSCs demonstrated a change into lung-specific Clara and type II pneumocyte cells when MSCs were cocultured with healthy lung tissue. Interestingly, in cocultures with irradiated lung biopsies, the percentage of MSCs changed into Clara and type II pneumocytes cells increased to 40±7% and 50±6% at 16 Gy irradiation dose and 30±5% and 40±8% at 20 Gy irradiation dose, respectively. These data suggest that MSCs to lung cell differentiation is possible without cell fusion. In addition, 16 and 20 Gy whole thorax irradiation doses that can cause varying levels of RILD, induced different percentages of MSCs to adopt lung cell phenotype compared with healthy lung tissue, providing encouraging outlook for RILD therapeutic intervention for ablative radiotherapy prescriptions.

Attempt of peripheral nerve reconstruction during lung cancer surgery.

Science.gov (United States)

Li, Hanyue; Hu, Yingjie; Huang, Jia; Yang, Yunhai; Xing, Kaichen; Luo, Qingquan

2018-05-01

Vagus nerve and recurrent laryngeal nerve (RLN) injury are not rare complications of lung cancer surgery and can cause lethal consequences. Until now, no optimal method other than paying greater attention during surgery has been available. Four patients underwent lung surgery that involved RLN or vagus nerve injury. The left RLN or vagus nerve was cut off and then reconstructed immediately during surgery. Two patients underwent direct anastomosis, while the remaining two underwent phrenic nerve replacing tension-relieving anastomosis. All patients were able to speak immediately after recovery. No or minimal glottal gap was observed during laryngoscopy conducted on the second day after surgery. Most patients achieved full recovery of voice quality. Immediate reconstruction of RLN is technically feasible and can be carried out with satisfying short-term and long-term outcomes. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

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.

Apoptosis in T lymphocytes from spleen tissue and peripheral blood of L. (L.) chagasi naturally infected dogs.

Science.gov (United States)

de Lima, Valéria Marçal Felix; Fattori, Karina Reinaldo; de Souza, Fausto; Eugênio, Flavia Rezende; dos Santos, Paulo Sérgio Patto; Rozza, Daniele Bernadete; Machado, Gisele Fabrino

2012-03-23

Dogs are the main domestic reservoirs of L. (L.) chagasi. Once in the vertebrate host, the parasite may cause visceral leishmaniasis, which can also be transmitted to humans. Infected symptomatic dogs show disorganization in the white pulp in spleen tissue and a reduction in T lymphocytes in peripheral blood. To investigate whether apoptosis is involved in white pulp disorganization and diminished T cell counts in peripheral blood, apoptotic T cells from the spleen and peripheral blood of dogs naturally infected with L. (L.) chagasi and presenting clinical manifestations were quantified and compared with healthy dogs. Thirteen symptomatic adult dogs infected by L. (L.) chagasi and six healthy dogs from a nonendemic area (controls) were included in the study. Samples from spleen and peripheral blood were used to quantify apoptosis in CD3 lymphocytes by flow cytometry using Anexin V and Multicaspase kits; the results were compared using the Mann Whitney test. The percentage of total T cells was lower in Leishmania infected dogs compared to healthy controls (Pspleen were higher in infected dogs than in controls (Pspleen white pulp and the percentage of apoptosis in the spleen. A significant effect on the level of white pulp morphological disorganization and percentage of apoptosis in spleen T cells was observed (F=20.45; P=0.0014). These data suggest that apoptosis is an important for the immunopathogenesis of canine visceral leishmaniasis. Copyright © 2011 Elsevier B.V. All rights reserved.

Guards at the gate: physiological and pathological roles of tissue-resident innate lymphoid cells in the lung.

Science.gov (United States)

Cheng, Hang; Jin, Chengyan; Wu, Jing; Zhu, Shan; Liu, Yong-Jun; Chen, Jingtao

2017-12-01

The lung is an important open organ and the primary site of respiration. Many life-threatening diseases develop in the lung, e.g., pneumonia, asthma, chronic obstructive pulmonary diseases (COPDs), pulmonary fibrosis, and lung cancer. In the lung, innate immunity serves as the frontline in both anti-irritant response and anti-tumor defense and is also critical for mucosal homeostasis; thus, it plays an important role in containing these pulmonary diseases. Innate lymphoid cells (ILCs), characterized by their strict tissue residence and distinct function in the mucosa, are attracting increased attention in innate immunity. Upon sensing the danger signals from damaged epithelium, ILCs activate, proliferate, and release numerous cytokines with specific local functions; they also participate in mucosal immune-surveillance, immune-regulation, and homeostasis. However, when their functions become uncontrolled, ILCs can enhance pathological states and induce diseases. In this review, we discuss the physiological and pathological functions of ILC subsets 1 to 3 in the lung, and how the pathogenic environment affects the function and plasticity of ILCs.

Assessment of airway lesion in obstructive lung diseases by CT

International Nuclear Information System (INIS)

Niimi, Akio; Matsumoto, Hisako; Ueda, Tetsuya; Mishima, Michiaki

2002-01-01

Airway lesion in obstructive pulmonary diseases, such as asthma or chronic obstructive pulmonary disease (COPD), has recently been assessed quantitatively. Especially in asthma, wall thickening of central airways, and its relation to the severity of disease or airflow obstruction has been clarified. Pathophysiologic importance of peripheral airway lesion has also been highlighted by pathologic or physiologic studies. However, direct evaluation of peripheral airway lesion is beyond resolutional limitation of CT. To assess airway trapping, an indirect CT finding of peripheral airway disease, by quantitative and semiquantitative measures and compare them with clinical indices such as pulmonary function, airway responsiveness, or airway inflammation. Patients with stable asthma (n=20) were studied. HRCT at 3 levels of both lungs were scanned. Low attenuation area (LAA)% and mean lung density were quantitatively assessed by an automatic method. Distribution of mosaic pattern was visually scored semiquantitatively. LAA% and mean lung density at full expiratory phase correlated with the degree of airflow obstruction. Mosaic score at full inspiratory phase correlated with the severity of disease and airflow obstruction. Expiratory/inspiratory ratio of mean lung density was also associated with airway responsiveness or residual volume/total lung capacity (RV/TLC). These CT findings may be useful as markers of asthma pathophysiology. (author)

Autoimmunity related to IgM monoclonal gammopathy of undetermined significance. Peripheral neuropathy and connective tissue sensibilization caused by IgM M-proteins

DEFF Research Database (Denmark)

Jønsson, V; Schrøder, H D; Nolsøe, C

1988-01-01

of them, including two siblings with a demyelinating peripheral neuropathy, the IgM was bound to the myelin-associated glycoprotein (MAG) of peripheral nerves. One had axonal neuropathy with IgM activity against the peri- and endoneurium, while another case with post-infectious neuritis had IgM activity......In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three...

Macrophages in lung tissue from patients with pulmonary emphysema express both inducible and endothelial nitric oxide synthase

NARCIS (Netherlands)

van Straaten, JFM; Postma, DS; Coers, W; Noordhoek, JA; Kauffman, HF; Timens, W

To provide information concerning a possible biologic role of nitric oxide (NO) in smoking-related emphysema, we performed immunohistochemical studies in lung tissue from control subjects and patients with mild and severe emphysema We studied the presence of inducible and endothelial NO synthases

Use of 67Ga citrate in the diagnosis of lung cancer

International Nuclear Information System (INIS)

Bogdasarov, Yu.B.; Zajtseva, T.I.; Gabuniya, R.I.; Abramov, V.F.

1981-01-01

A study was of the potentialities of 67 Ga citrate in the diagnosis of lung cancer, in differentiation from benign tumors and chronic inflammatory processes of the lungs. A total of 101 lung cancer patients were examined, of them 64 with central, and 37 with peripheral cancer. The results of radionuclide studies were correlated with those of surgery and with morphological findings. It has been established that in central cancer scintigraphy with 67 Ga citrate gives positive results in 87% of cases, and in peripheral cancer in 89%. This method is of great value for the diagnosis of cancer metastases to the mediastinal lymph nodes. No correlation between the intensity of 67 Ga citrate accumulation in lung tumors and their histological structure has been revealed [ru

Comprehensive evaluation of peripheral nerve regeneration in the acute healing phase using tissue clearing and optical microscopy in a rodent model.

Directory of Open Access Journals (Sweden)

Yookyung Jung

Full Text Available Peripheral nerve injury (PNI, a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout

Promoting peripheral myelin repair

OpenAIRE

Zhou, Ye; Notterpek, Lucia

2016-01-01

Compared to the central nervous system (CNS), peripheral nerves have a remarkable ability to regenerate and remyelinate. This regenerative capacity to a large extent is dependent on and supported by Schwann cells, the myelin-forming glial cells of the peripheral nervous system (PNS). In a variety of paradigms, Schwann cells are critical in the removal of the degenerated tissue, which is followed by remyelination of newly-regenerated axons. This unique plasticity of Schwann cells has been the ...

Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer

International Nuclear Information System (INIS)

Willumsen, Nicholas; Bager, Cecilie L; Leeming, Diana J; Smith, Victoria; Christiansen, Claus; Karsdal, Morten A; Dornan, David; Bay-Jensen, Anne-Christine

2014-01-01

Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a great potential for cancer. Levels of matrix metalloproteinase (MMP) generated fragments of type I collagen (C1M), of elastin (ELM), and of citrullinated vimentin (VICM) were measured in serum from patients with lung cancer (n = 40), gastrointestinal cancer (n = 25), prostate cancer (n = 14), malignant melanoma (n = 7), chronic obstructive pulmonary disease (COPD) (n = 13), and idiopathic pulmonary fibrosis (IPF) (n = 10), as well as in age-matched controls (n = 33). The area under the receiver operating characteristics (AUROC) was calculated and a diagnostic decision tree generated from specific cutoff values. C1M and VICM were significantly elevated in lung cancer patients as compared with healthy controls (AUROC = 0.98, P < 0.0001) and other cancers (AUROC = 0.83 P < 0.0001). A trend was detected when comparing lung cancer with COPD+IPF. No difference could be seen for ELM. Interestingly, C1M and VICM were able to identify patients with lung cancer with a positive predictive value of 0.9 and an odds ratio of 40 (95% CI = 8.7–186, P < 0.0001). Biomarkers specifically reflecting degradation of collagen type I and citrullinated vimentin are applicable for lung cancer patients. Our data indicate that biomarkers reflecting ECM and IMF protein dysregulation are highly applicable in the lung cancer setting. We speculate that these markers may aid in diagnosing and characterizing patients with lung cancer

Clinical prognostic factors and grading system for rib fracture following stereotactic body radiation therapy (SBRT) in patients with peripheral lung tumors.

Science.gov (United States)

Kim, Su Ssan; Song, Si Yeol; Kwak, Jungwon; Ahn, Seung Do; Kim, Jong Hoon; Lee, Jung Shin; Kim, Woo Sung; Kim, Sang-We; Choi, Eun Kyung

2013-02-01

Several studies reported rib fractures following stereotactic body radiation therapy (SBRT) for peripheral lung tumors. We tried to investigate risk factors and grading system for rib fractures after SBRT. Of 375 primary or metastatic lung tumors (296 patients) which were treated with SBRT at the Asan Medical Center (2006-2009), 126 lesions (118 patients) were adjacent to the chest-wall (6 months; these were investigated in the present retrospective study. Three to four fractional doses of 10-20 Gy were delivered to 85-90% iso-dose volume of the isocenter dose. Rib fracture grade was defined from follow-up CT scans as the appearance of a fracture line (Gr1), dislocation of the fractured rib by more than half the rib diameter (Gr2), or the appearance of adjacent soft tissue edema (Gr3). Chest wall pain was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Correlations between dose-volume data and the development of rib fracture were then analyzed. The Kaplan-Meier method, log-rank tests, and chi-square tests were used for statistical analysis. The median age of the patients was 69 years (range: 19-90). Over a median follow-up period of 22 months (range: 7-62), 48 cases of rib fracture were confirmed. Median time to rib fracture was 17 months (range: 4-52). The 2-year actuarial risk of rib fracture was 42.4%. Maximal grade was Gr1 (n=28), Gr2 (n=8), or Gr3 (n=15). The incidence of moderate to severe chest wall pain (CTCAE Gr ≥ 2) increased with maximal fracture grade (17.5% for Gr0-1 and 60.9% for Gr2-3; prib fracture in the present study. Efforts to decrease chest wall dose should be made to reduce the risk of the rib fracture, particularly in high-risk patients. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of lung elasticity on the sound propagation in the lung

International Nuclear Information System (INIS)

Yoneda, Takahiro; Wada, Shigeo; Nakamura, Masanori; Horii, Noriaki; Mizushima, Koichiro

2011-01-01

Sound propagation in the lung was simulated for gaining insight into its acoustic properties. A thorax model consisting of lung parenchyma, thoracic bones, trachea and other tissues was made from human CT images. Acoustic nature of the lung parenchyma and bones was expressed with the Biot model of poroelastic material, whereas trachea and tissues were modeled with gas and an elastic material. A point sound source of white noises was placed in the first bifurcation of trachea. The sound propagation in the thorax model was simulated in a frequency domain. The results demonstrated the significant attenuation of sound especially in frequencies larger than 1,000 Hz. Simulations with a stiffened lung demonstrated suppression of the sound attenuation for higher frequencies observed in the normal lung. These results indicate that the normal lung has the nature of a low-pass filter, and stiffening helps the sound at higher frequencies to propagate without attenuations. (author)

Interstitial Lung Disease

Science.gov (United States)

... propranolol (Inderal, Innopran), may harm lung tissue. Some antibiotics. Nitrofurantoin (Macrobid, Macrodantin, others) and ethambutol (Myambutol) can cause lung damage. Anti-inflammatory drugs. Certain anti-inflammatory drugs, such as rituximab ( ...

SU-F-T-150: Comparing Normal Tissue Irradiated Volumes for Proton Vs. Photon Treatment Plans On Lung Patients

Energy Technology Data Exchange (ETDEWEB)

Liu, A; Mohan, R; Liao, Z [UT MD Anderson Cancer Center, Houston, TX (United States)

2016-06-15

Purpose: The aim of this work is to compare the “irradiated volume” (IRV) of normal tissues receiving 5, 20, 50, 80 and 90% or higher of the prescription dose with passively scattered proton therapy (PSPT) vs. IMRT of lung cancer patients. The overall goal of this research is to understand the factors affecting outcomes of a randomized PSPT vs. IMRT lung trial. Methods: Thirteen lung cancer patients, selected randomly, were analyzed. Each patient had PSPT and IMRT 74 Gy (RBE) plans meeting the same normal tissue constraints generated. IRVs were created for pairs of IMRT and PSPT plans on each patient. The volume of iGTV, (respiratory motion-incorporated GTV) was subtracted from each IRV to create normal tissue irradiated volume IRVNT. The average of IRVNT DVHs over all patients was also calculated for both modalities and inter-compared as were the selected dose-volume indices. Probability (p value) curves were calculated based on the Wilcoxon matched-paired signed-rank test to determine the dose regions where the statistically significant differences existed. Results: As expected, the average 5, 20 and 50% IRVNT’s for PSPT was found to be significantly smaller than for IMRT (p < 0.001, 0.01, and 0.001 respectively). However, the average 90% IRVNT for PSPT was greater than for IMRT (p = 0.003) presumably due to larger penumbra of protons and the long range of protons in lower density media. The 80% IRVNT for PSPT was also larger but not statistically distinguishable (p = .224). Conclusion: PSPT modality has smaller irradiated volume at lower doses, but larger volume at high doses. A larger cohort of lung patients will be analyzed in the future and IRVNT of patients treated with PSPT and IMRT will be compared to determine if the irradiated volumes (the magnitude of “dose bath”) correlate with outcomes.

CT features of lung cancer associated with idiopathic pulmonary fibrosis

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Kim, Jun Hyoung; Song, Koun Sik; Lee, Deok Hee; Kim, Jin Suh; Lim, Tae Hwan

1996-01-01

It is well known that the incidence of lung cancer is high in patients with idiopathic pulmonary fibrosis(IPF). We analyzed the CT features of lung cancer associated with IPF. Retrospective analyzed the CT features of lung cancer associated with IPF. Retrospective analysis was performed in 23 patients with lung cancer(24 lung cancers) associated with IPF. The diagnosis of IPF was made by clinical and CT findings, and lung cancer was confirmed pathologically. We divided the location of lung cancer by lobar distribution and central or peripheral lung zone, and measured the size of mass. We classified the mediastinal lymph node enlargement by American Thoracic Society (ATS) mapping scheme. We evaluated the CT pattern of IPF. The subjects consisted of 6 cases of small cell carcinoma and 18 cases of non-small cell lung cancer. Non-small cell lung cancers were located in the right upper lobe in 5 cases, left upper lobe in 6 cases, right middle lobe in 1 case, right lower lobe in 9 cases, and left lower lobe in 3 cases. Twenty cancers(85%) were located in the peripheral lung zone. Eighteen cancers(73%) were surrounded by fibrotic lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3 cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung cancers. CT patterns of underlying IPF were honey-combing in 18 patients(78%) and mixed honey-combing and ground-glass opacity in 5 patients(22%). The lung cancer associated with IPF shows variable cell types. Most of the lung cancers were located peripherally, surrounded by end-stage fibrosis, and were associated with mediastinal lymph node enlargement

CT features of lung cancer associated with idiopathic pulmonary fibrosis

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Kim, Jun Hyoung; Song, Koun Sik; Lee, Deok Hee; Kim, Jin Suh; Lim, Tae Hwan [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

1996-01-01

It is well known that the incidence of lung cancer is high in patients with idiopathic pulmonary fibrosis(IPF). We analyzed the CT features of lung cancer associated with IPF. Retrospective analyzed the CT features of lung cancer associated with IPF. Retrospective analysis was performed in 23 patients with lung cancer(24 lung cancers) associated with IPF. The diagnosis of IPF was made by clinical and CT findings, and lung cancer was confirmed pathologically. We divided the location of lung cancer by lobar distribution and central or peripheral lung zone, and measured the size of mass. We classified the mediastinal lymph node enlargement by American Thoracic Society (ATS) mapping scheme. We evaluated the CT pattern of IPF. The subjects consisted of 6 cases of small cell carcinoma and 18 cases of non-small cell lung cancer. Non-small cell lung cancers were located in the right upper lobe in 5 cases, left upper lobe in 6 cases, right middle lobe in 1 case, right lower lobe in 9 cases, and left lower lobe in 3 cases. Twenty cancers(85%) were located in the peripheral lung zone. Eighteen cancers(73%) were surrounded by fibrotic lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung. The size of the mass ranged from 1 to 12 cm, and in 12 cases it was below 3 cm in diameter. Mediastinal lymph nodes were enlarged in 22 cases(92%) and classified as N2 or N3 in 15 cases out of 18 non-small cell lung cancers. CT patterns of underlying IPF were honey-combing in 18 patients(78%) and mixed honey-combing and ground-glass opacity in 5 patients(22%). The lung cancer associated with IPF shows variable cell types. Most of the lung cancers were located peripherally, surrounded by end-stage fibrosis, and were associated with mediastinal lymph node enlargement.

Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

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Giri, P.G.S.; Kimler, B.F.; Giri, U.P.; Cox, G.G.; Reddy, E.K.

1985-01-01

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. The authors conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation

Evaluation of small peripheral pulmonary lesions with thin slice computed tomography

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Yamada, Kouzo

1992-01-01

To evaluate the morphology of small peripheral pulmonary lesions, we studied thin-slice CT (TS-CT) images of 47 small peripheral pulmonary lesions (24 lung cancers, 23 benign lesions) in 47 patients. CT images were examined by two different window and level settings (window level; -600, window width; 1900 and window level; 50, window width; 300). In TS-CT images, findings of all lesions were classified into 3 different patterns (infiltrative type, solid with air-bronchogram type, homogeneous solid type) which were useful in diagnosing histology based on the growth pattern of the lesion. There was no lung cancer case in which calcification was diagnosed to be present on TS-CT. On the other hand, 5 of 9 inflammatory granulomas were recognized to contain calcium which was never seen on conventional CT. The results suggest that TS-CT may have a significant clinical role in diagnosing small peripheral pulmonary lesion by demonstrating macroscopic features and calcification. (author)

Identification of radiation response genes and proteins from mouse pulmonary tissues after high-dose per fraction irradiation of limited lung volumes.

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Jin, Hee; Jeon, Seulgi; Kang, Ga-Young; Lee, Hae-June; Cho, Jaeho; Lee, Yun-Sil

2017-02-01

The molecular effects of focal exposure of limited lung volumes to high-dose per fraction irradiation (HDFR) such as stereotactic body radiotherapy (SBRT) have not been fully characterized. In this study, we used such an irradiation system and identified the genes and proteins after HDFR to mouse lung, similar to those associated with human therapy. High focal radiation (90 Gy) was applied to a 3-mm volume of the left lung of C57BL6 mice using a small-animal stereotactic irradiator. As well as histological examination for lungs, a cDNA micro array using irradiated lung tissues and a protein array of sera were performed until 4 weeks after irradiation, and radiation-responsive genes and proteins were identified. For comparison, the long-term effects (12 months) of 20 Gy radiation wide-field dose to the left lung were also investigated. The genes ermap, epb4.2, cd200r3 (up regulation) and krt15, hoxc4, gdf2, cst9, cidec, and bnc1 (down-regulation) and the proteins of AIF, laminin, bNOS, HSP27, β-amyloid (upregulation), and calponin (downregulation) were identified as being responsive to 90 Gy HDFR. The gdf2, cst9, and cidec genes also responded to 20 Gy, suggesting that they are universal responsive genes in irradiated lungs. No universal proteins were identified in both 90 Gy and 20 Gy. Calponin, which was downregulated in protein antibody array analysis, showed a similar pattern in microarray data, suggesting a possible HDFR responsive serum biomarker that reflects gene alteration of irradiated lung tissue. These genes and proteins also responded to the lower doses of 20 Gy and 50 Gy HDFR. These results suggest that identified candidate genes and proteins are HDFR-specifically expressed in lung damage induced by HDFR relevant to SBRT in humans.

Synchrotron soft X-ray imaging and fluorescence microscopy reveal novel features of asbestos body morphology and composition in human lung tissues

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Polentarutti Maurizio

2011-02-01

Full Text Available Abstract Background Occupational or environmental exposure to asbestos fibres is associated with pleural and parenchymal lung diseases. A histopathologic hallmark of exposure to asbestos is the presence in lung parenchyma of the so-called asbestos bodies. They are the final product of biomineralization processes resulting in deposition of endogenous iron and organic matter (mainly proteins around the inhaled asbestos fibres. For shedding light on the formation mechanisms of asbestos bodies it is of fundamental importance to characterize at the same length scales not only their structural morphology and chemical composition but also to correlate them to the possible alterations in the local composition of the surrounding tissues. Here we report the first correlative morphological and chemical characterization of untreated paraffinated histological lung tissue samples with asbestos bodies by means of soft X-ray imaging and X-Ray Fluorescence (XRF microscopy, which reveals new features in the elemental lateral distribution. Results The X-ray absorption and phase contrast images and the simultaneously monitored XRF maps of tissue samples have revealed the location, distribution and elemental composition of asbestos bodies and associated nanometric structures. The observed specific morphology and differences in the local Si, Fe, O and Mg content provide distinct fingerprints characteristic for the core asbestos fibre and the ferruginous body. The highest Si content is found in the asbestos fibre, while the shell and ferruginous bodies are characterized by strongly increased content of Mg, Fe and O compared to the adjacent tissue. The XRF and SEM-EDX analyses of the extracted asbestos bodies confirmed an enhanced Mg deposition in the organic asbestos coating. Conclusions The present report demonstrates the potential of the advanced synchrotron-based X-ray imaging and microspectroscopy techniques for studying the response of the lung tissue to the

Esophagus and contralateral lung-sparing IMRT for locally advanced lung cancer in the community hospital setting

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Johnny eKao

2015-06-01

Full Text Available Background: The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue sparing IMRT can allow for safe dose escalation resulting in decreased acute and late toxicity. Methods: We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of 3-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT. From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity and overall survival.Results: Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 Gy vs. 60.8 Gy, p=0.04, patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, maximum esophagus and mean esophagus doses compared to patients treated with standard RT (p≤0.001. Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0% vs. 11%, p<0.001, acute grade ≥2 weight loss (2% vs. 16%, p=0.04, late grade ≥2 pneumonitis (7% vs. 21%, p=0.02. The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p=0.015.Conclusion: These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose volume constraints are feasible in the community hospital setting without sacrificing disease control.

Mechanisms of physical activity limitation in chronic lung diseases.

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Vogiatzis, Ioannis; Zakynthinos, George; Andrianopoulos, Vasileios

2012-01-01

In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i) the imbalance between ventilatory capacity and demand, (ii) the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii) the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea) and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients' quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.

Mechanisms of Physical Activity Limitation in Chronic Lung Diseases

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Ioannis Vogiatzis

2012-01-01

Full Text Available In chronic lung diseases physical activity limitation is multifactorial involving respiratory, hemodynamic, and peripheral muscle abnormalities. The mechanisms of limitation discussed in this paper relate to (i the imbalance between ventilatory capacity and demand, (ii the imbalance between energy demand and supply to working respiratory and peripheral muscles, and (iii the factors that induce peripheral muscle dysfunction. In practice, intolerable exertional symptoms (i.e., dyspnea and/or leg discomfort are the main symptoms that limit physical performance in patients with chronic lung diseases. Furthermore, the reduced capacity for physical work and the adoption of a sedentary lifestyle, in an attempt to avoid breathlessness upon physical exertion, cause profound muscle deconditioning which in turn leads to disability and loss of functional independence. Accordingly, physical inactivity is an important component of worsening the patients’ quality of life and contributes importantly to poor prognosis. Identifying the factors which prevent a patient with lung disease to easily carry out activities of daily living provides a unique as well as important perspective for the choice of the appropriate therapeutic strategy.

Optimization of extracranial stereotactic radiation therapy of small lung lesions using accurate dose calculation algorithms

International Nuclear Information System (INIS)

Dobler, Barbara; Walter, Cornelia; Knopf, Antje; Fabri, Daniella; Loeschel, Rainer; Polednik, Martin; Schneider, Frank; Wenz, Frederik; Lohr, Frank

2006-01-01

The aim of this study was to compare and to validate different dose calculation algorithms for the use in radiation therapy of small lung lesions and to optimize the treatment planning using accurate dose calculation algorithms. A 9-field conformal treatment plan was generated on an inhomogeneous phantom with lung mimics and a soft tissue equivalent insert, mimicking a lung tumor. The dose distribution was calculated with the Pencil Beam and Collapsed Cone algorithms implemented in Masterplan (Nucletron) and the Monte Carlo system XVMC and validated using Gafchromic EBT films. Differences in dose distribution were evaluated. The plans were then optimized by adding segments to the outer shell of the target in order to increase the dose near the interface to the lung. The Pencil Beam algorithm overestimated the dose by up to 15% compared to the measurements. Collapsed Cone and Monte Carlo predicted the dose more accurately with a maximum difference of -8% and -3% respectively compared to the film. Plan optimization by adding small segments to the peripheral parts of the target, creating a 2-step fluence modulation, allowed to increase target coverage and homogeneity as compared to the uncorrected 9 field plan. The use of forward 2-step fluence modulation in radiotherapy of small lung lesions allows the improvement of tumor coverage and dose homogeneity as compared to non-modulated treatment plans and may thus help to increase the local tumor control probability. While the Collapsed Cone algorithm is closer to measurements than the Pencil Beam algorithm, both algorithms are limited at tissue/lung interfaces, leaving Monte-Carlo the most accurate algorithm for dose prediction

Peripheral nerve magnetic stimulation: influence of tissue non-homogeneity

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Papazov Sava P

2003-12-01

Full Text Available Abstract Background Peripheral nerves are situated in a highly non-homogeneous environment, including muscles, bones, blood vessels, etc. Time-varying magnetic field stimulation of the median and ulnar nerves in the carpal region is studied, with special consideration of the influence of non-homogeneities. Methods A detailed three-dimensional finite element model (FEM of the anatomy of the wrist region was built to assess the induced currents distribution by external magnetic stimulation. The electromagnetic field distribution in the non-homogeneous domain was defined as an internal Dirichlet problem using the finite element method. The boundary conditions were obtained by analysis of the vector potential field excited by external current-driven coils. Results The results include evaluation and graphical representation of the induced current field distribution at various stimulation coil positions. Comparative study for the real non-homogeneous structure with anisotropic conductivities of the tissues and a mock homogeneous media is also presented. The possibility of achieving selective stimulation of either of the two nerves is assessed. Conclusion The model developed could be useful in theoretical prediction of the current distribution in the nerves during diagnostic stimulation and therapeutic procedures involving electromagnetic excitation. The errors in applying homogeneous domain modeling rather than real non-homogeneous biological structures are demonstrated. The practical implications of the applied approach are valid for any arbitrary weakly conductive medium.

Micromechanical model of lung parenchyma hyperelasticity

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Concha, Felipe; Sarabia-Vallejos, Mauricio; Hurtado, Daniel E.

2018-03-01

Mechanics plays a key role in respiratory physiology, as lung tissue cyclically deforms to bring air in and out the lung, a life-long process necessary for respiration. The study of regional mechanisms of deformation in lung parenchyma has received great attention to date due to its clinical relevance, as local overstretching and stress concentration in lung tissue is currently associated to pathological conditions such as lung injury during mechanical ventilation therapy. This mechanical approach to lung physiology has motivated the development of constitutive models to better understand the relation between stress and deformation in the lung. While material models proposed to date have been key in the development of whole-lung simulations, either they do not directly relate microstructural properties of alveolar tissue with coarse-scale behavior, or they require a high computational effort when based on real alveolar geometries. Furthermore, most models proposed to date have not been thoroughly validated for anisotropic deformation states, which are commonly found in normal lungs in-vivo. In this work, we develop a novel micromechanical model of lung parenchyma hyperelasticity using the framework of finite-deformation homogenization. To this end, we consider a tetrakaidecahedron unit cell with incompressible Neo-Hookean structural elements that account for the alveolar wall tissue responsible for the elastic response, and derive expressions for its effective coarse-scale behavior that directly depend on the alveolar wall elasticity, reference porosity, and two other geometrical coefficients. To validate the proposed model, we simulate the non-linear elastic response of twelve representative volume elements (RVEs) of lung parenchyma with micrometric dimensions, whose geometry is obtained from micrometric computed-tomography reconstructions of murine lungs. We show that the proposed micromechanical model accurately captures the RVEs response not only for isotropic

Plain radiologic findings of primary lung cancer by histologic types

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Lee, Young Seok; Park, Jae Hyung; Choi, Byung In; Yeon, Kyung Mo; Kim, Chu Wan

1983-01-01

Plain chest films are the most useful modality in diagnosis of primary lung cancer, but it is difficult to interpret the radiologic findings by histological types. Authors reviewed chest films of 324 cases of histologically confirmed primary lung cancer from January 1974 to April 1982 at Seoul National University. The results are as follows; 1. Incidence was most common in the 6th decade as 34.4%. Male to female sex radio was 3.8 : 1 and there was no sex difference in Adenocarcinoma. 2. Distribution of histologic types of primary lung cancers as follows; Squamous cell carcinoma 50.6%, Small cell carcinoma 22.5%, Large cell carcinoma 9.3%, Bronchogenic adeno carcinoma 10.5%, Bronchioloalveolar cell carcinoma 1.9%, Adenosquamous carcinoma 0.6%, Carcinoid tumor 0.3%, Adenoid cystic carcinoma 0.3%. 3. Radiologic findings by histologic types are follows; a) Squamous cell carcinoma commonly present as collapse (51.8%), peripheral mass (40.8%), pneumonitis (37.2%), hilar involvement (34.8%), and in single abnormality, peripheral mass (44.4%). b) Small cell carcinoma commonly present as hilar involvement (78.1%), mediastinal widening or mass (53.4%) and in single abnormality, hilar involvement (58.3%). c) Large cell carcinoma commonly present as hilar involvement (50%), pneumonia (46.7%), collapse (40%), peripheral mass (36.7%) and in single abnormality, large peripheral mass (33.3%). d) Bronchogenic adenocarcinoma commonly present as peripheral mass (44.1%), collapse (41.2%), pleural effusion (35.2%) and in single abnormality, peripheral mass (50%). e) Solitary peripheral mass commonly present as lobulation (48%) and spiculated margin (51%), but no specific findings by histologic types. Cavitary formation was most common in Squamous cell carcinoma

Eosinophilic Lung Disorders

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... problems characterized by having an increased number of eosinophils (white blood cells) in the lungs. These white ... category of pneumonias that feature increased numbers of eosinophils in the lung tissue. Pneumonia is an inflammatory ...

Calcium Channel Blockers and Esophageal Sclerosis: Should We Expect Exacerbation of Interstitial Lung Disease

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Charalampos Seretis

2012-01-01

Full Text Available Esophageal sclerosis is the most common visceral manifestation of systemic sclerosis, resulting in impaired esophageal clearance and retention of ingested food; in addition, co-existence of lung fibrosis with esophageal scleroderma is not uncommon. Both the progression of generalized connective tissue disorders and the damaging effect of chronic aspiration due to esophageal dysmotility appear to be involved in this procedure of interstitial fibrosis. Nifedipine is a widely prescribed calcium antagonist in a significant percentage of rheumatologic patients suffering from Raynaud syndrome, in order to inhibit peripheral vasospasm. Nevertheless, blocking calcium channels has proven to contribute to exacerbation of gastroesophageal reflux, which consequently can lead to chronic aspiration. We describe the case of severe exacerbation of interstitial lung disease in a 76-year-old female with esophageal sclerosis who was treated with oral nifedipine for Raynaud syndrome.

Changes in lung morphology and cell number in radiation pneumonitis and fibrosis: a quantitative ultrastructural study

International Nuclear Information System (INIS)

Vergara, J.A.; Raymond, U.; Thet, L.A.

1987-01-01

We used stereologic-morphometric techniques to obtain a detailed quantitative picture of the changes in lung ultrastructure of rats at 12 and 26 weeks after unilateral thoracic irradiation with 3000 cGy. At 12 weeks post-radiation, the total number type 1 epithelial cells, type 2 epithelial cells and capillary endothelial cells were decreased 50-70%, total type 1 epithelial and capillary surface areas were decreased 55-60%, and the total volume of intracapillary blood was decreased 75%. The interstitial cells and matrix together accounted for more than 9% of the peripheral lung tissue volume including air, compared to 3% in controls. The numerical density of interstitial cells was increased to 3-fold the control value. The numerical density of interstitial cells was increased to 3-fold the control value. Although fibroblasts still comprised the largest interstitial cell subgroup, the numerical density of mast cells was increased over 150-fold and other inflammatory and immune cells were increased to a lesser extent. At 26 weeks post-radiation, the number, volume, and surface area of the type 1 epithelium and capillary endothelium had further decreased to only 5-10% of control values. The total number of type 2 epithelial cells was reduced by 75% but the volume density was actually increased because of a 4-fold increase in the mean cell volume. The interstitial cells and matrix now comprised over 77% of total peripheral lung tissue volume including air as compared to 6% in controls. Mast cells and plasma cells comprised 11% and 19% of all interstitial cells respectively and the densities of these cells were 540 and 180-fold the control value respectively. The relation of these morphometric findings to the results of previous morphologic studies is discussed

Sterilization of Lung Matrices by Supercritical Carbon Dioxide.

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Balestrini, Jenna L; Liu, Angela; Gard, Ashley L; Huie, Janet; Blatt, Kelly M S; Schwan, Jonas; Zhao, Liping; Broekelmann, Tom J; Mecham, Robert P; Wilcox, Elise C; Niklason, Laura E

2016-03-01

Lung engineering is a potential alternative to transplantation for patients with end-stage pulmonary failure. Two challenges critical to the successful development of an engineered lung developed from a decellularized scaffold include (i) the suppression of resident infectious bioburden in the lung matrix, and (ii) the ability to sterilize decellularized tissues while preserving the essential biological and mechanical features intact. To date, the majority of lungs are sterilized using high concentrations of peracetic acid (PAA) resulting in extracellular matrix (ECM) depletion. These mechanically altered tissues have little to no storage potential. In this study, we report a sterilizing technique using supercritical carbon dioxide (ScCO2) that can achieve a sterility assurance level 10(-6) in decellularized lung matrix. The effects of ScCO2 treatment on the histological, mechanical, and biochemical properties of the sterile decellularized lung were evaluated and compared with those of freshly decellularized lung matrix and with PAA-treated acellular lung. Exposure of the decellularized tissue to ScCO2 did not significantly alter tissue architecture, ECM content or organization (glycosaminoglycans, elastin, collagen, and laminin), observations of cell engraftment, or mechanical integrity of the tissue. Furthermore, these attributes of lung matrix did not change after 6 months in sterile buffer following sterilization with ScCO2, indicating that ScCO2 produces a matrix that is stable during storage. The current study's results indicate that ScCO2 can be used to sterilize acellular lung tissue while simultaneously preserving key biological components required for the function of the scaffold for regenerative medicine purposes.

Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

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Castro-Sánchez, Adelaida María; Moreno-Lorenzo, Carmen; Matarán-Peñarrocha, Guillermo A.; Feriche-Fernández-Castanys, Belen; Granados-Gámez, Genoveva; Quesada-Rubio, José Manuel

2011-01-01

The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD) (Leriche-Fontaine classification) were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P < .05) in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg) and left lower limb (lower one-third of thigh and upper and lower one-third of leg). A significant difference (P < .05) was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P < .05) for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD. PMID:19933770

Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

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Adelaida María Castro-Sánchez

2011-01-01

Full Text Available The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD (Leriche-Fontaine classification were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P<.05 in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg and left lower limb (lower one-third of thigh and upper and lower one-third of leg. A significant difference (P<.05 was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P<.05 for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD.

Evaluation of the peripheral dose in stereotactic radiotherapy and radiosurgery treatments

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Di Betta, Erika; Fariselli, Laura; Bergantin, Achille; Locatelli, Federica; Del Vecchio, Antonella; Broggi, Sara; Fumagalli, Maria Luisa [Department of Neurosurgery, Division of Medical Physics, Fondazione IRCCS, Istituto Neurologico C. Besta, 20133 Milano (Italy); Department of Neurosurgery, Division of Radiotherapy, Fondazione IRCCS, Istituto Neurologico C. Besta, 20133 Milano (Italy); CyberKnife Centre, Centro Diagnostico Italiano, 20147 Milano (Italy); Division of Medical Physics, Fondazione IRCCS, Istituto S. Raffaele, 20132 Milano (Italy); Department of Neurosurgery, Division of Medical Physics, Fondazione IRCCS, Istituto Neurologico C. Besta, 20133 Milano (Italy)

2010-07-15

Purpose: The main purpose of this work was to compare peripheral doses absorbed during stereotactic treatment of a brain lesion delivered using different devices. These data were used to estimate the risk of stochastic effects. Methods: Treatment plans were created for an anthropomorphic phantom and delivered using a LINAC with stereotactic cones and a multileaf collimator, a CyberKnife system (before and after a supplemental shielding was applied), a TomoTherapy system, and a Gamma Knife unit. For each treatment, 5 Gy were prescribed to the target. Measurements were performed with thermoluminescent dosimeters inserted roughly in the position of the thyroid, sternum, upper lung, lower lung, and gonads. Results: Mean doses ranged from of 4.1 (Gamma Knife) to 62.8 mGy (LINAC with cones) in the thyroid, from 2.3 (TomoTherapy) to 30 mGy (preshielding CyberKnife) in the sternum, from 1.7 (TomoTherapy) to 20 mGy (preshielding CyberKnife) in the upper part of the lungs, from 0.98 (Gamma Knife) to 15 mGy (preshielding CyberKnife) in the lower part of the lungs, and between 0.3 (Gamma Knife) and 10 mGy (preshielding CyberKnife) in the gonads. Conclusions: The peripheral dose absorbed in the sites of interest with a 5 Gy fraction is low. Although the risk of adverse side effects calculated for 20 Gy delivered in 5 Gy fractions is negligible, in the interest of optimum patient radioprotection, further studies are needed to determine the weight of each contributor to the peripheral dose.

Evaluation of the peripheral dose in stereotactic radiotherapy and radiosurgery treatments

International Nuclear Information System (INIS)

Di Betta, Erika; Fariselli, Laura; Bergantin, Achille; Locatelli, Federica; Del Vecchio, Antonella; Broggi, Sara; Fumagalli, Maria Luisa

2010-01-01

Purpose: The main purpose of this work was to compare peripheral doses absorbed during stereotactic treatment of a brain lesion delivered using different devices. These data were used to estimate the risk of stochastic effects. Methods: Treatment plans were created for an anthropomorphic phantom and delivered using a LINAC with stereotactic cones and a multileaf collimator, a CyberKnife system (before and after a supplemental shielding was applied), a TomoTherapy system, and a Gamma Knife unit. For each treatment, 5 Gy were prescribed to the target. Measurements were performed with thermoluminescent dosimeters inserted roughly in the position of the thyroid, sternum, upper lung, lower lung, and gonads. Results: Mean doses ranged from of 4.1 (Gamma Knife) to 62.8 mGy (LINAC with cones) in the thyroid, from 2.3 (TomoTherapy) to 30 mGy (preshielding CyberKnife) in the sternum, from 1.7 (TomoTherapy) to 20 mGy (preshielding CyberKnife) in the upper part of the lungs, from 0.98 (Gamma Knife) to 15 mGy (preshielding CyberKnife) in the lower part of the lungs, and between 0.3 (Gamma Knife) and 10 mGy (preshielding CyberKnife) in the gonads. Conclusions: The peripheral dose absorbed in the sites of interest with a 5 Gy fraction is low. Although the risk of adverse side effects calculated for 20 Gy delivered in 5 Gy fractions is negligible, in the interest of optimum patient radioprotection, further studies are needed to determine the weight of each contributor to the peripheral dose.

CT-guided percutaneous conformal cryoablation for lung carcinoma

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Yueyong, Xiao; Bin, Wu; Xiao, Zhang; Hongjun, Li; Da, Yu; Jie, Li; Jun, Li [Department of Radiology, PLA General Hospital, Beijing (China)

2010-02-15

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

CT-guided percutaneous conformal cryoablation for lung carcinoma

International Nuclear Information System (INIS)

Xiao Yueyong; Wu Bin; Zhang Xiao; Li Hongjun; Yu Da; Li Jie; Li Jun

2010-01-01

Objective: To investigate the safety, efficacy and feasibility of CT-guided percutaneous conformal cryoablation for lung cancer. Methods: The inclusion criteria were: (1) Poor respiratory function and aged patients who can not bear the thoracic surgical operation. (2) Peripheral lung cancer involving the pleura and chest wall which can not be resected. (3) Residual tumor after other comprehensive treatment. (4) Focal lung cancer but the patient refused surgical resection. The exclusion criteria were: (1) Multifocal lesions. (2) Lesion close to mediastinum with possible risk of vessel injury. (3) Severe impairment of pulmonary functions, the maximum voluntary ventilation is less than 39%. (4) Repeated cough or dyspnea, can not cooperate with the procedure. (5) Poor systemic conditions, cachexia or bleeding. Totally, 76 lung carcinoma lesions on 66 patients were treated by CT-guided percutaneous conformal cryoablation using 17 G cryoprobes. The maximum diameters of the tumors ranged from 1.5 cm to 1.6 cm. For the tumors with the maximum diameter less than 3.0 cm, they were treated by double-needle clamping cryoablation. For those with the maximum diameter between 3.0 and 5.0 cm, they were treated by multiple-needle conformal cryoablation. For those with the maximum diameter larger than 5.0 cm, they were treated with multiple-needle conformal cyroablation, with the needle distance less than 1.5 cm. All the patients were followed-up 6 to 24 months after the procedure using contrast-enhanced CT to evaluate the tumor size and enhancement. Results: For 18 cases with the maximum diameters less than 3.0 cm, CT scan during the procedure showed that the frozen areas extended beyond the edge of the lesions more than 1.0 cm, the lesion attenuated, narrow-band-like encircled translucency around the lesions and 'target sign' with ground-glass density of the peripheral lung tissue. There was no enhancement during the first 1 st, 3 rd month follow-up, only fibrosis scar in 6 th

Estimation of Lung Ventilation

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Ding, Kai; Cao, Kunlin; Du, Kaifang; Amelon, Ryan; Christensen, Gary E.; Raghavan, Madhavan; Reinhardt, Joseph M.

Since the primary function of the lung is gas exchange, ventilation can be interpreted as an index of lung function in addition to perfusion. Injury and disease processes can alter lung function on a global and/or a local level. MDCT can be used to acquire multiple static breath-hold CT images of the lung taken at different lung volumes, or with proper respiratory control, 4DCT images of the lung reconstructed at different respiratory phases. Image registration can be applied to this data to estimate a deformation field that transforms the lung from one volume configuration to the other. This deformation field can be analyzed to estimate local lung tissue expansion, calculate voxel-by-voxel intensity change, and make biomechanical measurements. The physiologic significance of the registration-based measures of respiratory function can be established by comparing to more conventional measurements, such as nuclear medicine or contrast wash-in/wash-out studies with CT or MR. An important emerging application of these methods is the detection of pulmonary function change in subjects undergoing radiation therapy (RT) for lung cancer. During RT, treatment is commonly limited to sub-therapeutic doses due to unintended toxicity to normal lung tissue. Measurement of pulmonary function may be useful as a planning tool during RT planning, may be useful for tracking the progression of toxicity to nearby normal tissue during RT, and can be used to evaluate the effectiveness of a treatment post-therapy. This chapter reviews the basic measures to estimate regional ventilation from image registration of CT images, the comparison of them to the existing golden standard and the application in radiation therapy.

A clinical study on carcinoembryonic antigens in patients with squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Moriya, Hiroshi; Satoh, Toshihiko; Kimura, Kazuei; Togawa, Takafumi; Higuchi, Yoshisuke

1986-01-01

The serum levels of carcinoembryonic antigens (CEA) were determined in 57 patients with squamous cell carcinoma of the lung. The overall positive ratio was 45.6 %. The patients were classified into 2 groups, a peripheral type and a central type, according to bronchoscopic findings. The positive ratio in patients with peripheral type was 66.7 %. And the ratio with central type was 26.7 %. There was a significant difference (p < 0.005) between peripheral type and central type of squamous cell carcinoma of the lung. (author)

SARS – Lung Pathology

Indian Academy of Sciences (India)

Dry nonproductive cough – may show minimal lung infiltration. Recovery; * Lungs get fluid in bronchi- droplets infective and +ve for virus in culture and PCR. May also have co-infection with chlamydia/metapneumoviruses. Recovery; * Lung tissue destroyed due to ? immunological/cytokine mediated damage-Recovery ...

Diverse Epitope Specificity, Immunodominance Hierarchy, and Functional Avidity of Effector CD4 T Cells Established During Priming Is Maintained in Lung After Influenza A Virus Infection.

Science.gov (United States)

Richards, Katherine A; DiPiazza, Anthony T; Rattan, Ajitanuj; Knowlden, Zackery A G; Yang, Hongmei; Sant, Andrea J

2018-01-01

One of the major contributions to protective immunity to influenza viruses that is provided by virus-specific CD4 T cells is delivery of effector function to the infected lung. However, there is little known about the selection and breadth of viral epitope-specific CD4 T cells that home to the lung after their initial priming. In this study, using a mouse model of influenza A infection and an unbiased method of epitope identification, the viral epitope-specific CD4 T cells elicited after infection were identified and quantified. We found that a very diverse specificity of CD4 T cells is primed by infection, including epitopes from hemagglutinin, neuraminidase, matrix protein, nucleoprotein, and non-structural protein-1. Using peptide-specific cytokine EliSpots, the diversity and immunodominance hierarchies established in the lung-draining lymph node were compared with specificities of CD4 T cells that home to the lung. Our studies revealed that CD4 T cells of all epitope specificities identified in peripheral lymphoid tissue home back to the lung and that most of these lung-homing cells are localized within the tissue rather than the pulmonary vasculature. There is a striking shift of CD4 T cell functionality that enriches for IFN-γ production as cells are primed in the lymph node, enter the lung vasculature, and finally establish residency in the tissue, but with no apparent shifts in their functional avidity. We conclude that CD4 T cells of broad viral epitope specificity are recruited into the lung after influenza infection, where they then have the opportunity to encounter infected or antigen-bearing antigen-presenting cells.

Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

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Hwang, Ji Young; Randall, Troy D; Silva-Sanchez, Aaron

2016-01-01

Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

Short Chain Fatty Acids in the Colon and Peripheral Tissues: A Focus on Butyrate, Colon Cancer, Obesity and Insulin Resistance

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Sean M. McNabney

2017-12-01

Full Text Available Increased dietary fiber consumption has been associated with many beneficial effects, including amelioration of obesity and insulin resistance. These effects may be due to the increased production of short chain fatty acids, including propionate, acetate and butyrate, during fermentation of the dietary fiber in the colon. Indeed, oral and dietary supplementation of butyrate alone has been shown to prevent high fat-diet induced obesity and insulin resistance. This review focuses on sources of short chain fatty acids, with emphasis on sources of butyrate, mechanisms of fiber and butyrate metabolism in the gut and its protective effects on colon cancer and the peripheral effects of butyrate supplementation in peripheral tissues in the prevention and reversal of obesity and insulin resistance.

Identification and validation of differentially expressed transcripts by RNA-sequencing of formalin-fixed, paraffin-embedded (FFPE) lung tissue from patients with Idiopathic Pulmonary Fibrosis.

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Vukmirovic, Milica; Herazo-Maya, Jose D; Blackmon, John; Skodric-Trifunovic, Vesna; Jovanovic, Dragana; Pavlovic, Sonja; Stojsic, Jelena; Zeljkovic, Vesna; Yan, Xiting; Homer, Robert; Stefanovic, Branko; Kaminski, Naftali

2017-01-12

Idiopathic Pulmonary Fibrosis (IPF) is a lethal lung disease of unknown etiology. A major limitation in transcriptomic profiling of lung tissue in IPF has been a dependence on snap-frozen fresh tissues (FF). In this project we sought to determine whether genome scale transcript profiling using RNA Sequencing (RNA-Seq) could be applied to archived Formalin-Fixed Paraffin-Embedded (FFPE) IPF tissues. We isolated total RNA from 7 IPF and 5 control FFPE lung tissues and performed 50 base pair paired-end sequencing on Illumina 2000 HiSeq. TopHat2 was used to map sequencing reads to the human genome. On average ~62 million reads (53.4% of ~116 million reads) were mapped per sample. 4,131 genes were differentially expressed between IPF and controls (1,920 increased and 2,211 decreased (FDR < 0.05). We compared our results to differentially expressed genes calculated from a previously published dataset generated from FF tissues analyzed on Agilent microarrays (GSE47460). The overlap of differentially expressed genes was very high (760 increased and 1,413 decreased, FDR < 0.05). Only 92 differentially expressed genes changed in opposite directions. Pathway enrichment analysis performed using MetaCore confirmed numerous IPF relevant genes and pathways including extracellular remodeling, TGF-beta, and WNT. Gene network analysis of MMP7, a highly differentially expressed gene in both datasets, revealed the same canonical pathways and gene network candidates in RNA-Seq and microarray data. For validation by NanoString nCounter® we selected 35 genes that had a fold change of 2 in at least one dataset (10 discordant, 10 significantly differentially expressed in one dataset only and 15 concordant genes). High concordance of fold change and FDR was observed for each type of the samples (FF vs FFPE) with both microarrays (r = 0.92) and RNA-Seq (r = 0.90) and the number of discordant genes was reduced to four. Our results demonstrate that RNA sequencing of RNA

Peripheral and central localization of the nesfatin-1 receptor using autoradiography in rats

International Nuclear Information System (INIS)

Prinz, Philip; Goebel-Stengel, Miriam; Teuffel, Pauline; Rose, Matthias; Klapp, Burghard F.; Stengel, Andreas

2016-01-01

Nesfatin-1 was recently identified and introduced as food intake-regulatory hormone. Soon thereafter, mounting evidence indicated a much broader role for nesfatin-1 with an involvement in the regulation of food intake, gastrointestinal motility, glucose homeostasis, blood pressure and stress. Despite the growing knowledge on the physiological regulation and functions of nesfatin-1, the receptor mediating these effects remains to be characterized. Therefore, the aim of this study was to investigate the peripheral and central localization of the nesfatin-1 receptor by autoradiography. Male Sprague–Dawley rats were used and peripheral as well as brain tissue was processed for "1"2"5I-nesfatin-1 autoradiography. In peripheral tissues, an autoradiographic signal was observed in the gastric mucosa of corpus and antrum, in duodenum, jejunum and ileum, while no signal was detected in the colon. Preabsorption of "1"2"5I-nesfatin-1 with non-labeled nesfatin-1 greatly diminished the autoradiographic signal in the stomach indicating specificity (−32%, p < 0.001). A displacement assay showed an effective concentration by which 50% of "1"2"5I-nesfatin-1 bound to the receptor (EC_5_0) in the gastric corpus of 80 pM. Moreover, autoradiography was observed in endocrine tissues including the pituitary, pancreas, adrenal gland, testis and visceral adipose tissue. In addition, also heart, skeletal muscle, lung, liver and kidney showed autoradiographic signals. In the brain, strong "1"2"5I-nesfatin-1 autoradiography was detected in the cortex, paraventricular nucleus of the hypothalamus, area postrema, dorsal motor nucleus of the vagus nerve and cerebellum. Based on the distribution of nesfatin-1 autoradiography, nesfatin-1 is a pleiotropic hormone that is involved in the regulation of several homeostatic functions. - Highlights: • Although our knowledge on nesfatin-1 is increasing, the receptor is still unknown. • "1"2"5I-nesfatin-1 autoradiography was detected in (a

Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

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Daniel Antunes Silva Pereira

2015-04-01

Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

CT-guided needle biopsy in the diagnosis of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: a rare combination.

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Tian, Panwen; Wang, Ye; Wan, Chun; Shen, Yongchun; Wen, Fuqiang

2015-01-01

We represent a rare case of lung adenocarcinoma accompanied by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). The patient was a 66-year-old male presented with 1 month history of recurrent cough and hemoptysis. Chest CT showed solitary ground-glass opacity (GGO) in the upper lobe of the right lung and mediastinal lymph node enlargement in station 3p. A CT-guided transthoracic needle biopsy was performed. Tissue specimens of the GGO revealed a typical adenocarcinoma. Histopathologic diagnosis of mediastinal lymph node was extranodal marginal zone lymphoma of MALT. Because of its rarity, extranodal marginal zone lymphoma of MALT should be considered in the differential diagnosis when we encounter mediastinal lymphadenopathy in patients with lung adenocarcinoma.

Illumina MiSeq 16S amplicon sequence analysis of bovine respiratory disease associated bacteria in lung and mediastinal lymph node tissue.

Science.gov (United States)

Johnston, Dayle; Earley, Bernadette; Cormican, Paul; Murray, Gerard; Kenny, David Anthony; Waters, Sinead Mary; McGee, Mark; Kelly, Alan Kieran; McCabe, Matthew Sean

2017-05-02

Bovine respiratory disease (BRD) is caused by growth of single or multiple species of pathogenic bacteria in lung tissue following stress and/or viral infection. Next generation sequencing of 16S ribosomal RNA gene PCR amplicons (NGS 16S amplicon analysis) is a powerful culture-independent open reference method that has recently been used to increase understanding of BRD-associated bacteria in the upper respiratory tract of BRD cattle. However, it has not yet been used to examine the microbiome of the bovine lower respiratory tract. The objective of this study was to use NGS 16S amplicon analysis to identify bacteria in post-mortem lung and lymph node tissue samples harvested from fatal BRD cases and clinically healthy animals. Cranial lobe and corresponding mediastinal lymph node post-mortem tissue samples were collected from calves diagnosed as BRD cases by veterinary laboratory pathologists and from clinically healthy calves. NGS 16S amplicon libraries, targeting the V3-V4 region of the bacterial 16S rRNA gene were prepared and sequenced on an Illumina MiSeq. Quantitative insights into microbial ecology (QIIME) was used to determine operational taxonomic units (OTUs) which corresponded to the 16S rRNA gene sequences. Leptotrichiaceae, Mycoplasma, Pasteurellaceae, and Fusobacterium were the most abundant OTUs identified in the lungs and lymph nodes of the calves which died from BRD. Leptotrichiaceae, Fusobacterium, Mycoplasma, Trueperella and Bacteroides had greater relative abundances in post-mortem lung samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Leptotrichiaceae, Mycoplasma and Pasteurellaceae showed higher relative abundances in post-mortem lymph node samples collected from fatal cases of BRD in dairy calves, compared with clinically healthy calves without lung lesions. Two Leptotrichiaceae sequence contigs were subsequently assembled from bacterial DNA-enriched shotgun sequences

Peripheral ossifying fibroma

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Ameet Mani

2010-01-01

Full Text Available The peripheral ossifying fibroma (POF is an exophytic gingival mass of fibrous connective tissue covered with a surface epithelium associated with the formation of randomly dispersed foci of a mineralized product consisting of bone, cementum-like tissue, or dystrophic calcifications having a recurrent rate of nearly 20%. It is one of the most common reactive gingival lesions, which have often been called by the generic term "epulis." This case report describes the clinical and histopathological findings of POF, its differential diagnosis, and treatment.

Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer