tbuckley/cabot-search huggingface dataset:
Absence of the intestinal microbiota exacerbates hepatobiliary disease in a murine model of primary sclerosing cholangitis
Authors: James H. Tabibian, Steven P. O'Hara, Christy E. Trussoni, Pamela S. Tietz, Patrick L. Splinter, Taofic Mounajjed, Lee R. Hagey, Nicholas F. LaRusso
Journal: Hepatology (2015)

Primary sclerosing cholangitis (PSC) is a chronic, idiopathic, fibroinflammatory cholangiopathy. The role of the microbiota in PSC etiopathogenesis may be fundamentally important, yet remains obscure. We tested the hypothesis that germ‐free (GF) mutltidrug resistance 2 knockout (mdr2 −/− ) mice develop a distinct PSC phenotype, compared to conventionally housed (CV) mdr2 −/− mice. Mdr2 −/− mice (n = 12) were rederived as GF by embryo transfer, maintained in isolators, and sacrificed at 60 days in parallel with age‐matched CV mdr2 −/− mice. Serum biochemistries, gallbladder bile acids, and liver sections were examined. Histological findings were validated morphometrically, biochemically, and by immunofluorescence microscopy (IFM). Cholangiocyte senescence was assessed by p16 INK4a in situ hybridization in liver tissue and by senescence‐associated β‐galactosidase staining in a culture‐based model of insult‐induced senescence. Serum biochemistries, including alkaline phosphatase, aspartate aminotransferase, and bilirubin, were significantly higher in GF mdr2 −/− ( P &lt; 0.01). Primary bile acids were similar, whereas secondary bile acids were absent, in GF mdr2 −/− mice. Fibrosis, ductular reaction, and ductopenia were significantly more severe histopathologically in GF mdr2 −/− mice ( P &lt; 0.01) and were confirmed by hepatic morphometry, hydroxyproline assay, and IFM. Cholangiocyte senescence was significantly increased in GF mdr2 −/− mice and abrogated in vitro by ursodeoxycholic acid (UDCA) treatment. Conclusions : GF mdr2 −/− mice exhibit exacerbated biochemical and histological features of PSC and increased cholangiocyte senescence, a characteristic and potential mediator of progressive biliary disease. UDCA, a commensal microbial metabolite, abrogates senescence in vitro . These findings demonstrate the importance of the commensal microbiota and its metabolites in protecting against biliary injury and suggest avenues for future studies of biomarkers and therapeutic interventions in PSC. (H epatology 2016;63:185–196)
Abstract 1464: Cardiac Myosin Binding Protein-C (cMyBP-C) Directly Modulates Actomyosin Binding and Kinetics Independent of LMM and S2 Binding.
Authors: Walid Saber, Kelly J Begin, David M Warshaw, Peter VanBuren
Journal: Circulation (2007)

BACKGROUND: While mutations in cMyBP-C constitute a common cause of FHC, its role in sarcomere contraction remains unclear. cMyBP-C binds to actin, titin and the S2 and LMM proteolytic domains of myosin. Through its numerous binding interactions cMyBP-C may act as a tether, restricting myosin and/or actomyosin function. We directly tested this hypothesis in the in vitro motility assay using either whole myosin or the myosin subfragments, HMM and S1 (which lack LMM and LMM-S2, respectively). METHODS AND RESULTS: The motility assay is an in vitro model of muscle contraction in which thin filaments are propelled across a myosin coated surface. The addition of cMyBP-C to the motility assay resulted in a concentration dependent reduction in actin filament velocity when using either whole myosin, HMM or S1, demonstrating that cMyBP-C inhibits thin filament velocity independent of LMM or S2 binding. Using whole myosin and thin filaments reconstituted with troponin/tropomyosin, the addition of cMyBP-C resulted in a 29% reduction in maximal velocity (P=0.002) with no effect on maximal force. At sub-maximal calcium, the pCa50 for velocity was increased (6.64 ± 0.06 vs. control, 6.44 ± 0.03, P=0.003) whereas the pCa50 for force was decreased (6.25 ± 0.09 vs. control, 6.55 ± 0.02, P=0.008). Thin filament activation by myosin strong-binding demonstrated an increased amount of myosin required to half maximally activate the thin filament in the presence of cMyBP-C, indicating that myosin binding to the thin filament is reduced with cMyBP-C. These findings were supported by co-sedimentation experiments which demonstrate that cMyBP-C competes with S1 for actin binding in the presence of ATP, with no effect on S1/actin binding in the absence of ATP. Finally, while the number of cross-bridges interacting with the thin filament is rate limiting for velocity at shorter filament lengths, this was not observed at longer filament lengths indicating that cMyBP- C directly modulates the kinetics of actomyosin. CONCLUSIONS: The effects of cMyBP-C on velocity and force demonstrate that cMyBP-C does not simply act as a tether but likely affects both the kinetics and the recruitment of myosin cross-bridges through its direct interaction with the myosin head and/or the actin filament.
Prevalence and persistence of antibodies to herpes viruses, Chlamydia pneumoniae and Helicobacter pylori in Alaskan Eskimos: the GOCADAN Study
Authors: J. Zhu, M. Davidson, M. Leinonen, P. Saikku, C.A. Gaydos, D.A. Canos, K.A. Gutman, B.V. Howard, S.E. Epstein
Journal: Clinical Microbiology and Infection (2006)
Functional Integrity of Cryopreserved Human Monocytes&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: R S Weiner, S J Normann
Journal: JNCI Journal of the National Cancer Institute (1981)

Human peripheral blood monocytes collected by semicontinuous flow centrifugation were cryopreserved in varying concentrations of dimethyl sulfoxide (DMSO). Optimum protection from lethal cryoinjury was achieved with 7.5-10% DMSO. Compared to fresh cells, cryopreserved cells retained 80% of their chemotactic responsiveness and fructose-6-phosphate shunt activity after stimulation by zymosan. Fresh and cryopreserved human monocytes had comparable but low levels of cytotoxic activity against P-815 murine mastocytoma cells in vitro.
Sensitivity and specificity of airway hyperreactivity (AHR) based on methacholine challenge (MCH) tests - Comparison of sGeff with FEV1 and MEF50 as target parameter
Authors: Richard Kraemer, Gabi Giger, Thomas Sigrist, Martin Frey
Journal: European Respiratory Journal (2012)

Rationale.  Airway hyperreactivity (AHR) is a characteristic feature of asthma, and methacholine challenge tests (MCT) are well established, mostly defining a fall of 20% in FEV 1  as PC 20 . In contrast to this spirometric technique, whole-body plethysmography features the possibility to evaluate changes of airway dynamics concomitantly with changes of lung volumes (see also abstract 850929).   Objectives.  Assessment of sensitivity and specificity of MCT, comparing changes of effective specific airway conductances (sG eff , sG 0.5 , sG tot ) with changes effected to FEV 1  and MEF 50 .   Methods.  Data from 140 test persons (asthmatics and controls; 59 males; 81 females; age: 11 to 82 y), in whom MCH was administered during 3 consecutive cumulative challenge levels (P1:0.2 mg; P2:1.0 mg; P3:2.2 mg) computerized by the APS system, were retrospectively evaluated.   Results.  Highest response rates were found for sG eff PD , 50  (82.1%) and sG tot PD , 50  (77.1%), lowest for FEV 1 PD 20  (34.3%), and intermediate for MEF 50 PD 50  (45%). sG eff  reached its PD 50  at 0.56±0.48 mg, FEV 1  its PD 20  only at .94±.57 mg MCH. Sensitivity of MCH-tests (s) and specificity (f) were obtained as follows: sG eff  (s: 95.7%; f: 80.0%), sG tot  (s: 91.3%; f: 88.0%), FEV 1  (s: 38.3%; f: 84.0%) and MEF 50 : (s: 48.7%; f: 72.0%).   Conclusions.  In comparison to FEV 1 , assessment of AHR by sG eff  and sG tot  reached their PD at much lower MCH doses, in a much higher percentage of tests. The advantage of MCT by plethysmography, measuring changes of airway dynamics in relation to changes of the volume history, features the advantage to perform MCT with better safety for the patients.
Differences in Nuclear Glucocorticoid Binding Between Corticoid-Sensitive and Corticoid-Resistant Lymphocytes of Mouse Lymphoma P1798 and Stabilization of Nuclear Hormone Receptor Complexes With Carbobenzoxy-L-phenylalanine&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John Stevens, Vee-Wan Stevens, Jonathan Rhodes, German Steiner
Journal: JNCI Journal of the National Cancer Institute (1978)

Nuclear glucocorticoid binding was compared in the corticoid-sensitive (CS) and corticoid-resistant (CR) strains of mouse lymphoma P1798. Purified nuclei were isolated from tumor cells that had been incubated with [3H]triamcinolone acetonide (TA) for 60 minutes at 37° C. A 0.6-M solution of KCI extracted 80–90% [3H]TA from both CS and CR nuclei, but only 15–20% of [3H]sterold in the salt extract was bound to macromoleculeS as judged by gel filtration (Sephadex G-25). Breakdown of hormone receptor complexes could be prevented by the inclusion of the chymotrypsin inhibitor carbobenzoxy-L-phenylalanine In the 0.8-M KCI extraction buffer. Under these conditions, 70% of [3H]TA extracted from CS nuclei and 80% of [3H]TA extracted from CR nuclei were recovered in the void volume of the Sephadex columns, correspondlng to 6,100±1,560 molecules of [3H]TA per CS nucleus and 3,900±650 molecule. of [3H]TA per CR nucleus. Low concentrations of monovalent (KCI), divalent (Mg2+ or Ca2+), or polyvalent (spermidine) cations consistently extracted a higher percentage of [3H]TA from CS than from CR nuclei, which suggested that interactions of [3H]TA with the nucleus might have been weaker in the sensitive cells. The effects of Mg2+ and spermidine on release of [3H]TA from CS nuclei were neither additive nor temperature-dependent. Furthermore, the magnitude of release was not influenced by the concentration of [3H]TA (1±30 nM) to which the cells were exposed nor by the length of time (10±80 min) they were incubated with the hormone. Experiments in which mixtures of unlabeled CS and labeled CR nuclei (or vice versa) were extracted with 4 mM MgCI2 suggested that CS nuclei did not contain diffusable Mg2+ -dependent [3H)TA-releasing activity nor CR nuclei, an inhibitor of release. Elucidation of the biochemical basis for the differences in nuclear glucocorticoid binding between CS and CR P1798 lymphocytes may shed some light on the mechanism of resistance of the CR cells to glucocorticoid administration
Competing Risk of Cardiac Status and Renal Function During Hospitalization for Acute Decompensated Heart Failure
Authors: Khibar Salah, Wouter E Kok, Luc W Eurlings, Paulo Bettencourt, Joana M Pimenta, Marco Metra, Valerio Verdiani, Jan G Tijssen, Yigal M Pinto
Journal: JACC Heart Failure (2015)
Pulmonary sparganosis mansoni: A case report
Authors: Kebin Cheng, Beilan Gao, Jinming Ming, Jinfu Xu
Journal: European Respiratory Journal (2013)

Reported here is a case of a 32-year-old Chinese female infected by sparganum mansoni, a kind of tapeworm, showing migratory path shadows in both lungs. She complained of intermittent cough and blood stained sputum. She also had a history of eating raw seafood and a preference for raw bullfrogs. Antibody blood tests conducted by the Chinese Centre for Disease Control Institute of Parasitic Disease and Parasitology showed a suspiciously positive Sparganum mansoni antibody response. It was later rechecked using both a blood sample and a bronchoscopic lavage sample and it was confirmed that sparganum mansoni antibodies were positive. A diagnosis of Infection with Pulmonary Sparganosis mansoni was then made. After two oral courses praziquantel, her symptoms and radiological lesions significantly improved. As far as the authors are aware, this is the third case of sparganosis limited to the lung in the world. The current report presents the first detailed treatment on a case of Pulmonary Sparganosis mansoni.
Serine Protease Activation Essential for Endothelial–Mesenchymal Transition in Vascular Calcification
Authors: Jiayi Yao, Pierre J. Guihard, Ana M. Blazquez-Medela, Yina Guo, Jeremiah H. Moon, Medet Jumabay, Kristina I. Boström, Yucheng Yao
Journal: Circulation Research (2015)

Endothelial cells have the ability to undergo endothelial-mesenchymal transitions (EndMTs), by which they acquire a mesenchymal phenotype and stem cell-like characteristics. We previously found that EndMTs occurred in the endothelium deficient in matrix γ-carboxyglutamic acid protein enabling endothelial cells to contribute cells to vascular calcification. However, the mechanism responsible for initiating EndMTs is not fully understood.To determine the role of specific serine proteases and sex determining region Y-box 2 (Sox2) in the initiation of EndMTs.In this study, we used in vivo and in vitro models of vascular calcification to demonstrate that serine proteases and Sox2 are essential for the initiation of EndMTs in matrix γ-carboxyglutamic acid protein-deficient endothelium. We showed that expression of a group of specific serine proteases was highly induced in endothelial cells at sites of vascular calcification in Mgp null aortas. Treatment with serine protease inhibitors decreased both stem cell marker expression and vascular calcification. In human aortic endothelial cells, this group of serine proteases also induced EndMTs, and the activation of proteases was mediated by Sox2. Knockdown of the serine proteases or Sox2 diminished EndMTs and calcification. Endothelial-specific deletion of Sox2 decreased expression of stem cell markers and aortic calcification in matrix γ-carboxyglutamic acid protein-deficient mice.Our results suggest that Sox2-mediated activation of specific serine proteases is essential for initiating EndMTs, and thus, may provide new therapeutic targets for treating vascular calcification.
Ethambutol-induced pulmonary infiltrates with eosinophilia and skin involvement
Authors: PC Wong, WW Yew, CF Wong, HY Choi
Journal: European Respiratory Journal (1995)

A 67 year old woman presented with miliary tuberculosis. She was treated with streptomycin, isoniazid, rifampicin, ethambutol and pyrazinamide. However, she developed rifampicin-induced thrombocytopenia after 6 weeks of treatment, and skin rash, blood eosinophilia and pulmonary infiltrates after 8 weeks of therapy. The latter was found to be ethambutol related. Additional evidence, including blood and sputum eosinophilia and the rapidity of its response to corticosteroid, suggested that the pulmonary infiltrates might also be eosinophilic in nature. To the best of our knowledge, this constitutes the first report of such adverse drug reaction, induced by ethambutol.
First Report of a Phase Ii Trial of Irinotecan Plus S-1 (Iris) with Cetuximab (Iris/Cet) in Pre-Treated Patients with Kras Wild Type of Metastatic Colorectal Cancer (Mcrc): Hgcsg0902
Authors: O. Muto, S. Yuki, M. Nakamura, A. Hosokawa, T. Kato, I. Iwanaga, K. Hatanaka, Y. Tsuji, A. Sato, K. Eto, K. Furukawa, H. Okuda, M. Onodera, K. Fujikawa, M. Kudo, S. Yokoyama, T. Honda, Y. Sakata, Y. Komatsu
Journal: Annals of Oncology (2014)
Endothelial CD99 signals through soluble adenylyl cyclase and PKA to regulate leukocyte transendothelial migration
Authors: Richard L. Watson, Jochen Buck, Lonny R. Levin, Ryan C. Winger, Jing Wang, Hisashi Arase, William A. Muller
Journal: The Journal of Experimental Medicine (2015)

CD99 is a critical regulator of leukocyte transendothelial migration (TEM). How CD99 signals during this process remains unknown. We show that during TEM, endothelial cell (EC) CD99 activates protein kinase A (PKA) via a signaling complex formed with the lysine-rich juxtamembrane cytoplasmic tail of CD99, the A-kinase anchoring protein ezrin, and soluble adenylyl cyclase (sAC). PKA then stimulates membrane trafficking from the lateral border recycling compartment to sites of TEM, facilitating the passage of leukocytes across the endothelium. Pharmacologic or genetic inhibition of EC sAC or PKA, like CD99 blockade, arrests neutrophils and monocytes partway through EC junctions, in vitro and in vivo, without affecting leukocyte adhesion or the expression of relevant cellular adhesion molecules. This is the first description of the CD99 signaling pathway in TEM as well as the first demonstration of a role for sAC in leukocyte TEM.
Hyperlipidemia and transplantation
Authors: J D Pirsch, A M D'Alessandro, H W Sollinger, S J Knechtle, A Reed, M Kalayoglu, F O Belzer
Journal: Journal of the American Society of Nephrology (1992)

Hyperlipidemia is a well-recognized complication of renal transplantation. In long-term survivors of renal transplantation, cardiovascular disease accounts for the majority of patient deaths. In the cyclosporine era, cardiovascular disease has surpassed infection as the number one cause of death. Risk factors in the transplant population for hyperlipidemia include age, male sex, diabetes, prednisone dose, graft impairment, obesity, and antihypertensive therapy. Recently, cyclosporine has been implicated as an aggravating factor in the development of hyperlipidemia after transplantation, although its role has been controversial. Because renal transplant recipients have other significant risk factors for the development of coronary artery disease, the amelioration of hyperlipidemia may improve long-term patient survival. Because most late deaths occur in patients with a functioning graft, long-term graft survival could also be improved. The role of corticosteroids in the development of hyperlipidemia is well established. Recent studies employing corticosteroid withdrawal after transplantation have shown a marked reduction in cholesterol despite the use of cyclosporine. Data on corticosteroid withdrawal in living related transplants at our center show a significant reduction in total cholesterol after steroid withdrawal. Data from heart transplant recipients under corticosteroid-free protocols show a similar reduction in total cholesterol. Other treatments for hyperlipidemia include diet and cholesterol-lowering agents, such as Mevacor (lovastatin; Merck Sharp & Dohme, West Point, PA). The efficacy of lowering cholesterol in this high-risk population is unknown.
Acute kidney injury in China: a cross-sectional survey
Authors: Li Yang, Guolan Xing, Li Wang, Yonggui Wu, Suhua Li, Gang Xu, Qiang He, Jianghua Chen, Menghua Chen, Xiaohua Liu, Zaizhi Zhu, Lin Yang, Xiyan Lian, Feng Ding, Yun Li, Huamin Wang, Jianqin Wang, Rong Wang, Changlin Mei, Jixian Xu, Rongshan Li, Juan Cao, Liang Zhang, Yan Wang, Jinhua Xu, Beiyan Bao, Bicheng Liu, Hongyu Chen, Shaomei Li, Yan Zha, Qiong Luo, Dongcheng Chen, Yulan Shen, Yunhua Liao, Zhengrong Zhang, Xianqiu Wang, Kun Zhang, Luojin Liu, Peiju Mao, Chunxiang Guo, Jiangang Li, Zhenfu Wang, Shoujun Bai, Shuangjie Shi, Yafang Wang, Jinwei Wang, Zhangsuo Liu, Fang Wang, Dandan Huang, Shun Wang, Shuwang Ge, Quanquan Shen, Ping Zhang, Lihua Wu, Miao Pan, Xiting Zou, Ping Zhu, Jintao Zhao, Minjie Zhou, Lin Yang, Wenping Hu, Jing Wang, Bing Liu, Tong Zhang, Jianxin Han, Tao Wen, Minghui Zhao, Haiyan Wang
Journal: The Lancet (2015)
T regulatory cells in exacerbation control of chronic obstructive pulmonary disease of mild and moderate stage
Authors: Oleg Enikeev, Svetlana Enikeeva, Damir Enikeev
Journal: European Respiratory Journal (2012)

Aim: to investigate the levels of peripheral CD4(+)CD25(++) regulatory T cells and the inflammatory and anti inflammatory cytokines in exacerbation dynamics of mild and moderate stage of chronic obstructive pulmonary disease (AECOPD) patients.  Methods: Peripheral blood samples were collected from 20 patients with mild AECOPD and 21 patients with moderate AECOPD, aged (55,6±3,2; 51±3 respectively) and 20 man from control group. Lymphocytes were isolated by two-color labeled monoclonal antibodies flow cytometry to examine the quantities and percentage of CD4+CD25+ T cell, CD4+CD25++ (CD4(+)Treg), CD3+CD19- T cell, CD3+CD4+ T cell, CD3+CD8+ T cell, respectively. Enzyme immunodetection was used to detect the expression of interleukin-10 (IL-10), tumor necrosis factor alpha (TNF-alpha), procalcitonin (PCT) and C-reactive protein (CRP). Mann-Whitney test was used for comparison between data before and after treatment and control group.  Results. In patients with mild and moderate AECOPD take place significant decreasing of Tregulatory cells (CD4+CD25++) from 3,3±0,8% in control to 1,13±0,17% and 1,3±0,12%%, respectively (p
Accumulation of hyaluronan in bronchoalveolar lavage fluid is independent of iron-, complement- and granulocyte-depletion in bleomycin-induced alveolitis in the rat
Authors: O Nettelbladt, K Lundberg, A Tengblad, R Hallgren
Journal: European Respiratory Journal (1990)

Previous studies on bleomycin-induced alveolitis in rats have demonstrated a transient histological accumulation of hyaluronan (hyaluronate or hyaluronic acid) in the alveolar interstitium, corresponding to increases in hyaluronan (HA) levels in bronchoalveolar lavage (BAL) fluid and lung tissue extracts. The accumulation of HA was related to the influx of inflammatory cells, especially polymorphonucleated cells (PMNs) in BAL fluid and the increase in lung water. In this study we have investigated the influence of iron, complement and PMN dependent mechanisms on the early connective response of the lung in the bleomycin rat model. Iron depletion had no effect on HA or the cellular composition of lavage fluid recovered on day 4 post bleomycin. Treatment of bleomycin-injured rats with cobra venom factor (CVF), totally neutralized complement haemolytic activity but had no effect on lavage HA or the cell invasion in BAL. Treatment with anti-neutrophil serum (ANS), reduced blood and lavage PMN by 70-80%, but had no influence on HA levels in BAL. These results suggest that regulatory mechanisms other than those dependent on iron, complement activation or PMN recruitment are responsible for HA accumulation in this fibrosing alveolitis animal model.
Nasal inflammation and sleep quality with continuous positive airway pressure (CPAP) therapy in obstructive sleep apnoea
Authors: Mohammed AlAhmari, Christine Mikelsons, Raymond Sapsford, Jadwiga Wedzicha, John Hurst
Journal: European Respiratory Journal (2013)

Background:  CPAP can cause undesirable nasal side effects which can significantly compromise therapy [1].  Aims and objectives:  Over a 6 month period, the association between nasal inflammation using nasal wash interleukin (IL-6) and Epworth sleepiness scale (ESS) was assessed.  Methods:  22 patients were recruited from the Sleep Medicine service at the Royal Free Campus, London UK with new, polysomnographically confirmed OSA. The following assessments were performed at baseline (no CPAP) and at 1, 3 and 6 months post-CPAP; nasal wash interleukin (IL)-6 and the ESS to assess the degree of daytime sleepiness. Pearson correlation was conducted to assess the relationship between nasal inflammation and sleep quality. A P value  Results:  The 22 OSA patients (mean age±SD: 59.5±7.5 years) had an apnea hypopnea index [AHI events/h] of mean (SD) 30.2±15.9.  We found a significant relationship between increased (IL)-6 and degree of daytime sleepiness, Pearson [r = 0.492, p=0.023].   Conclusion:  Our results show that nasal inflammation relates to reduced sleep quality in OSA.