tbuckley/cabot-search huggingface dataset:
Synthetic response of stimulated respiratory epithelium: Modulation by prednisolone and iKK2 inhibition
Authors: Lucy B. Woodman, Wing Yan Heidi Wan, Roberta Milone, Ken Grace, Ana Sousa, Rick Williamson, Christopher Brightling
Journal: European Respiratory Journal (2012)

Background:  The airway epithelium plays a central role in wound repair & host defence & is implicated in the immunopathogenesis of asthma. Whether there are intrinsic differences between the synthetic capacity of epithelial cells derived from asthmatics & healthy controls & how this mediator release is modulated by anti-inflammatory therapy remains uncertain.  Aims:  We sought to examine the synthetic function of epithelial cells from different locations in the airway tree from subjects with & without asthma & to determine the effects of anti-inflammatory therapies upon this synthetic capacity.  Methods:  Primary epithelial cells were derived from 17 asthmatics & 16 controls. The release of 13 mediators from nasal & bronchial basal & air-liquid interface differentiated epithelial cells before & after stimulation with IL-1β, IL-1β & IFNγ or Poly-IC (TLR3 agonist) were measured using MSD or ELISA & the effects of prednisolone, rosiglitazone, & an inhibitor of nuclear factor Κ-β2 (IKK2i) were determined.  Results:  The pattern of release of cytokines & chemokines was significantly different between nasal & bronchial basal & differentiated epithelial cells, but not between health & disease. Stimulation of the epithelial cells caused marked up-regulation of most mediators which were broadly corticosteroid unresponsive, but attenuated by IKK2i.  Conclusion:  Synthetic capacity of primary airway epithelial cells varies between location & degree of differentiation, but is not disease specific. Activation of epithelial cells by pro-inflammatory cytokines & TLR3 agonism is attenuated by IKK2i, but not corticosteroids suggesting that IKK2i may represent an important novel therapy for asthma.
Interkingdom gene fusions
Authors: Yuri I Wolf, Alexey S Kondrashov, Eugene V Koonin
Journal: Genome biology (2000)

Genome comparisons have revealed major lateral gene transfer between the three primary kingdoms of life - Bacteria, Archaea, and Eukarya. Another important evolutionary phenomenon involves the evolutionary mobility of protein domains that form versatile multidomain architectures. We were interested in investigating the possibility of a combination of these phenomena, with an invading gene merging with a pre-existing gene in the recipient genome.Complete genomes of fifteen bacteria, four archaea and one eukaryote were searched for interkingdom gene fusions (IKFs); that is, genes coding for proteins that apparently consist of domains originating from different primary kingdoms. Phylogenetic analysis supported 37 cases of IKF, each of which includes a 'native' domain and a horizontally acquired 'alien' domain. IKFs could have evolved via lateral transfer of a gene coding for the alien domain (or a larger protein containing this domain) followed by recombination with a native gene. For several IKFs, this scenario is supported by the presence of a gene coding for a second, stand-alone version of the alien domain in the recipient genome. Among the genomes investigated, the greatest number of IKFs has been detected in Mycobacterium tuberculosis, where they are almost always accompanied by a stand-alone alien domain. For most of the IKF cases detected in other genomes, the stand-alone counterpart is missing.The results of comparative genome analysis show that IKF formation is a real, but relatively rare, evolutionary phenomenon. We hypothesize that IKFs are formed primarily via the proposed two-stage mechanism, but other than in the Actinomycetes, in which IKF generation seems to be an active, ongoing process, most of the stand-alone intermediates have been eliminated, perhaps because of functional redundancy.
Recognition of Damaged DNA: Structure and Dynamic Markers
Authors: Markus W. Germann, Christopher N. Johnson, Alexander M. Spring
Journal: Medicinal Research Reviews (2010)

Abstract DNA damage, a consequence of external factors and inherent metabolic processes, is omnipresent. Nature has devised multiple strategies to safeguard the genetic information and developed intricate repair mechanisms and pathways to reverse an array of different DNA lesions, including mismatches. Failure of the DNA repair systems may result in mutation, premature ageing, and cancer. In this review, we focus on structural and dynamic aspects of detection of lesions in base excision and mismatch repair. A thorough understanding of repair, pathways, and regulation is necessary to develop strategies for targeting DNA‐related pathologies. © 2010 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 659–683, 2012
Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing, 2005–2007
Authors: L. Ren, R. Gonzalez, Z. Wang, Z. Xiang, Y. Wang, H. Zhou, J. Li, Y. Xiao, Q. Yang, J. Zhang, L. Chen, W. Wang, Y. Li, T. Li, X. Meng, Y. Zhang, G. Vernet, G. Paranhos-Baccalà, J. Chen, Q. Jin, J. Wang
Journal: Clinical Microbiology and Infection (2009)
Asthma management in five European countries: doctors′ knowledge, attitudes and prescribing behaviour
Authors: P. Lagerløv, C.C.M Veninga, M Muskova, E. Hummers-Pradier, C Stålsby Lundborg, M Andrew, F.M Haaijer-Ruskamp, None on behalf of the Drug Education Project (dep) group
Journal: European Respiratory Journal (2000)

The aim of the study was to examine the relationship between guideline recommendations on asthma management, and the performance of doctors in five different European health care contexts. Knowledge, attitudes and prescribing behaviour of doctors recruited to an educational project was investigated. A total of 698 general practitioners from Germany, The Netherlands, Norway and Sweden, and 94 specialists from the Slovak Republic participated. A questionnaire was used to assess their knowledge and attitudes. Antiasthmatic drugs dispensed to their patients reflected their prescribing behaviour. In response to questions on how to treat chronic asthma, most doctors were in agreement with guideline recommendations. In practice, however, the proportion of asthma patients receiving inhaled steroids varied almost twofold, ranging 31% in Germany to 58% in The Netherlands. On questions related to exacerbation of asthma, German and Slovakian doctors often preferred treatment with antibiotics to steroids. They also more often associated yellow-green sputum with bacterial infection. In conclusion, although many doctors in different health care contexts have accepted the recommendations given in guidelines, the proportion of their patients treated accordingly differed. German and Slovakian doctors seem to attach less importance to the inflammatory features of asthma than the doctors from the other three European countries.
A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B.
Authors: A P Chahinian, K J Propert, J H Ware, B Zimmer, M C Perry, V Hirsh, A Skarin, S Kopel, J F Holland, R L Comis
Journal: Journal of Clinical Oncology (1989)

The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.
Bidirectional transendothelial migration of monocytes across hepatic sinusoidal endothelium shapes monocyte differentiation and regulates the balance between immunity and tolerance in liver
Authors: Henning W. Zimmermann, Tony Bruns, Chris J. Weston, Stuart M. Curbishley, Evaggelia Liaskou, Ka‐Kit Li, Yazid J. Resheq, Paul W. Badenhorst, David H. Adams
Journal: Hepatology (2015)

Monocytes are versatile cells that can fulfill proinflammatory and anti-inflammatory functions when recruited to the liver. Recruited monocytes differentiate into tissue macrophages and dendritic cells, which sample antigens and migrate to lymph nodes to elicit T-cell responses. The signals that determine monocyte differentiation and the role of hepatic sinusoidal endothelial cells (HSECs) in this process are poorly understood. HSECs are known to modulate T-cell activation, which led us to investigate whether transendothelial migration of monocytes across HSECs influences their phenotype and function. Subsets of blood-derived monocytes were allowed to transmigrate across human HSECs into a collagen matrix. Most migrated cells remained in the subendothelial matrix, but ~10% underwent spontaneous basal to apical transendothelial migration. The maturation, cytokine secretion, and T-cell stimulatory capacity of reverse transmigrating (RT) and subendothelial (SE) monocytes were compared. SE monocytes were mainly CD16(-) , whereas 75%-80% of RT monocytes were CD16(+) . SE monocytes derived from the CD14(++) CD16(-) subset and exhibited high phagocytic activity, whereas RT monocytes originated from CD14(++) CD16(+) and CD14(+) CD16(++) monocytes, displayed an immature dendritic cell-like phenotype (CD11c(pos) HLA-DR(pos) CD80lo CD86lo ), and expressed higher levels of chemokine (C-C motif) receptor 8. Consistent with a dendritic cell phenotype, RT monocytes secreted inflammatory cytokines and induced antigen-specific CD4(+) T-cell activation. In contrast, SE monocytes suppressed T-cell proliferation and activation and exhibited endotoxin tolerance. Transcriptome analysis underscored the functional differences between SE and RT monocytes.Migration across HSECs shapes the subsequent fate of monocytes, giving rise to anergic macrophage-like cells in tissue and the release of immunocompetent pre-dendritic cells into the circulation.
Exposure to ozone shifts natural killer cells co-cultured with epithelial cells towards a type II phenotype
Authors: Loretta Müller, Missy Brigthon, Ilona Jaspers
Journal: European Respiratory Journal (2012)

Nasal epithelial cells (NECs) are one of the first targets for air pollutants, such as ozone. Previous studies in our lab have demonstrated that natural killer (NK) cells are an important immune cell population in the nose. NK cells and NECs interact with each other via receptor-ligand interactions as well as soluble mediators. NK cells are an important source for type I cytokines, like IFN-γ, but also type II cytokines, like IL-4. Yet, whether and how exposure to air pollutants affects this interactions and changes NK cell phenotypes is not known.

Differentiated NECs were exposed to ozone (O3; 0.4ppm, 4hrs). 2hrs after exposure peripheral blood NK cells were added to the apical side to establish co-cultures. At 24hrs post-exposure, both cell types were examined for changes in surface marker and intracellular cytokine expression by flow cytometry.

Exposure to O3 significantly increased the expression of the NK cell ligands MICA/B and ULBP3 on NECs in co-cultures. NK cell surface markers NKG2D, NKp46 and CXCR3 were not affected by co-culture with O3-exposed NECs. Expression of CD16, a cytotoxicity marker, and Granzyme B, a marker of cytolytic NK cells, were enhanced in co-cultures with O3-exposed NECs. Intracellular IFN-γ was decreased and IL-4 was significantly increased in NK cells co-cultured with O3-exposed NECs.

O3-induced changes in the microenvironment of NECs change NK cell phenotypes from a type I (high IFN-γ) to a type II (high IL-4) immunophenotype. These data indicate that exposure of NEC to O3 changes interactions with resident immune cells, such as NK cells, shifting the immune phenotype which likely affects the ability to fight invading pathogens.
Efficacy of Biological-Targeted Treatments in Takayasu Arteritis
Authors: Arsene Mekinian, Cloé Comarmond, Mathieu Resche-Rigon, Tristan Mirault, Jean Emmanuel Kahn, Marc Lambert, Jean Sibilia, Antoine Néel, Pascal Cohen, Miguel Hie, Sabine Berthier, Isabelle Marie, Christian Lavigne, Marie Anne Vandenhende, Géraldine Muller, Zahir Amoura, Hervé Devilliers, Sébastien Abad, Mohamed Hamidou, Loïc Guillevin, Robin Dhote, Bertrand Godeau, Emmanuel Messas, Patrice Cacoub, Olivier Fain, David Saadoun
Journal: Circulation (2015)

The goal of this work was to assess the safety and efficacy of biologics (ie, tumor necrosis factor-α antagonists and tocilizumab) in patients with Takayasu arteritis.This was a retrospective, multicenter study of the characteristics and outcomes of 49 patients with Takayasu arteritis (80% female; median age, 42 years [20-55 years] treated by tumor necrosis factor-α antagonists [80%] or tocilizumab [20%]) and fulfilling American College of Rheumatology or Ishikawa criteria. Factors associated with complete response were assessed. Eighty-eight percent of patients with Takayasu arteritis were inadequately controlled with or were intolerant to conventional immunosuppressive therapy (median number, 3 [1-5]). Overall response (ie, complete and partial) to biological-targeted treatments at 6 and 12 months was 75% and 83%, respectively. There were significantly lower C-reactive protein levels at the initiation of biological-targeted treatments (22 mg/L [10-46 mg/L] versus 58 mg/L [26-76 mg/L]; P=0.006) and a trend toward fewer immunosuppressants drugs used before biologics (P=0.054) in responders (ie, complete or partial responders) relative to nonresponders to biological-targeted treatments. C-reactive protein levels and daily prednisone dose significantly decreased after 12 months of biological-targeted treatments (30 versus 6 mg/L [P<0.05] and 15 versus 7.5 mg [P<0.05] at baseline and 12 months, respectively). The 3-year relapse-free survival was 90.9% (83.5%-99%) over the biological treatment period compared with 58.7% (43.3%-79.7%; P=0.0025) with disease-modifying antirheumatic drugs. No difference in efficacy was found between tumor necrosis factor-α antagonists and tocilizumab. After a median follow-up of 24 months (2-95 months), 21% of patients experienced adverse effects, with biological-targeted treatments discontinued in 6.6% of cases.This nationwide study shows a high efficacy of biological-targeted treatments in refractory patients with Takayasu arteritis with an acceptable safety profile.
Relationships between exhaled nitric oxide and lung function profiles in severe asthma
Authors: Qingling Zhnag, E. Guo, Naijian Li, Mengzhang He, Jing Li, Jingping Zheng
Journal: European Respiratory Journal (2013)

OBJECTIVE:

To examine whether fractional exhaled nitric oxide (FeNO) levels are associated with lung function in severe asthmatics.

METHOD:

A total of 24 non-smoking stable severe asthmatics underwent an assessment that included FeNO measurements, spirometry [including forced expiratory volume at the first second (FEV1), forced volume capacity (FVC), forced expiratory flow at 25–75% of volume capacity (FEF25–75), peak expiratory flow(PEF)], bronchial reversibility and patient characteristics, i.e. asthma control questionnaire 5 (ACQ5), gender, obesity (defined as BMI ≥ 25 kg/m2), nasal disease, duration of asthma, exacerbation times in the past year. All patients had been attending the clinic for at least 6 months and had undergone a Severe Asthma Protocol for confirmation of the diagnosis of severe asthma.

RESULTS:

Mean FeNo of the subjects was 40±31.33ppb.FeNO levels varied according to the gender. A positive correlation was found between FeNO and FVC,PEF and ΔFEV1 after bronchodilator. There appears to be no correlation between FeNO and nasal diseases, ACQ5, duration of asthma and excarbation times in the past year.

![Figure][1] 



CONCLUSION:

FeNO levels varied according to the gender. A positive correlation was found between FeNO and FVC,PEF and ΔFEV1 after broncodilator. The value of FeNO measurement in severe asthma need further additional research.

 [1]: pending:yes
Endoscopic management of benign tracheobronchial tumors: Ten-year experience from a large, single center case series
Authors: Gianni Galluccio, Simone Scarlata, Paolo Graziano, Raffaele Dello Iacono, Paolo Battistoni, Sandro Batzella, Gabriele Lucantoni, Raffaele Antonelli Incalzi
Journal: European Respiratory Journal (2013)

Introduction: benign tracheo-bronchial tumors(TBT)usually induce airway obstruction and occasionally suffocation.  Surgery is the recommended therapy,but it may be challenging and burdened with high frequency of complications. Rigid bronchoscopic management of benign TBT is a potential alternative. However, few data are available on the epidemiology of these lesions and on the safety of endoscopic treatment.  We report on a series of 58 benign TBT diagnosed out of 15,120 total tracheo-bronchial endoscopic procedures performed from 2000 to 2012.  Results:Thirty-four(61%)TBT occurred in males and mean age at diagnosis was 59.4 years(SD 7.2).Most(65%)grew distally to a main stem bronchus,13(23.3%) were located into a main bronchus and 7(11%)were tracheal.Adenomas (2/58),amarthomas(21/58)and schwannomas(2/58)often located distal to the main bronchus (2/2,17/21 and 1/2,respectively),whereas leiomiomas(4/58) preferentially located in the trachea or in a main bronchus(3/4).All tumors were diagnosed in patients older than 60 years except for leiomiomas,schwannomas,and papillomas that also occurred in younger patients.Amartomas,leiomiomas,and polyps were frequent amongst males, the two cases of schwannomas occurred in females.  Tumor eradication was obtained after a single procedure in 61% of cases,in 8.5% of cases a second or a third intervention was needed.Seven patients had to be addressed to open surgery for definitive eradication.No severe complications nor deaths were observed.  Conclusions: data obtained from a large case series confirm that interventional rigid bronchoscopy for benign TBT is simple and safe,and this option should be considered beside open thoracic surgery.
Differential Enhancement of R-Type Virus Particles in Polyoma-Transformed BHK-21 Cells by Dimethyl Sulfoxide&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Alexander L. Kisch, Robert O. Kelley, Betty J. Eberle
Journal: JNCI Journal of the National Cancer Institute (1972)

Significantly more R-type virus particles (RTP) were observed by electron microscopy in a cloned population (CI-I) of cells transformed by polyoma virus (PV) than in the nontransformed parent cell population (P<0.02). Short-term propagation in medium containing 2% (v/v) dimethyl sulfoxide increased significantly the RTP in CI-I cells (P<0.01) but not in BHK-21 cells. These observations suggest that RTP may interact with PV and possibly other DNA tumor viruses in the induction, maintenance, or expression of functional alterations associated with cell transformation.
Characteristics of XDR-TB patients in Israel: 2000-2010
Authors: Daniele Bendayan, Atara Hendler, Klementy Litman
Journal: European Respiratory Journal (2011)

Background:  In the last years, Israel experiences mass immigration from countries highly endemic for tuberculosis such as the Former Soviet Union (FSU) and the proportion of multiple drug resistance tuberculosis (MDR-TB) significantly increased. XDR-TB which is defined as MDR-TB that is resistant to any fluoroquinolones and one of the second lines inject able drugs, is a lethal disease that was reported even in well controlled countries.The aim of this study was to assess the burden and the characteristics of Israeli XDR-TB patients.   Method:  Charts of XDR-TB patients, hospitalized in the National Tuberculosis Center from year 2000 to 2010, were retrospectively reviewed. Demographic, clinical and bacteriological characteristics, genotype analyze, co morbidity, and treatment outcome were summarized.   Results:  9 patients were identified with a median age of 35 and male predominance (80%). All the patients came from the FSU and only one was HIV co infected. At diagnosis time, all the patients had advanced pulmonary disease and were highly contagious. Only 33% of them were previously treated, and 55% of them were diagnosed as XDR-TB at presentation. Treatment was individual, based on drug susceptibility pattern. Unfortunately, 70% of the patients died in a period of two years. Molecular genotyping analyze revealed the W Beijing family strains (80%).   Conclusion:  XDR-TB in Israel is still a rare disease that occurs essentially in the immigrate population. It is strongly associated with the W Beijing family strains with a high rate of death. Efforts should be made to find new effective drugs and to better understand the relationship between the W Beijing family strains and the human population.
New Method for Detection of Mouse Mammary Tumor Virus. II. Effect of Administration of Lactating Mammary Tissue Extracts on Incidence of Hyperplastic Mammary Nodules in BALB/cCrgl Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Satyabrata Nandi
Journal: JNCI Journal of the National Cancer Institute (1963)

One- to 2-day old male and female BALB/cCrgl mice received intraperitoneal injections of lactating mammary tissue extracts from various MTV-free and MTV-carrying strains of mice. Control mice of both sexes were given injections of saline. Beginning at 36 days of age, intact female and gonadectomized male mice were treated daily for 90 days with a “noduligenic” hormone combination containing estradiol plus deoxycorticosterone acetate. The animals were killed either on the 22d or on the 36th day after the last hormone injection. Hyperplastic mammary nodules were absent from control mice given saline, and from all but one of the mice given injections of tissue extracts from MTV-free strains. These nodules were present, however, in the mammary glands of 39 of the 46 mice with injections of tissue extracts from MTV-carrying strains. These experiments thus demonstrate that the hormonal induction of rapid nodule formation in BALB/cCrgl mice is a suitable method for the qualitative detection of the mouse mammary tumor virus.