tbuckley/cabot-search huggingface dataset:
Diagnostic yield of transbronchial cryobiopsy in diffuse lung disease: A randomised trial
Authors: Virginia Pajares, Carmen Puzo, Enrique Lerma, Angeles Montero, David Ramos-Barbon, Oscar Amor, Angels Gil de Bernabé, Tomás Franquet, Vicente Plaza, Joaquim Sanchis, Alfons Torrego
Journal: European Respiratory Journal (2013)

Introduction:  A cryoprobe can harvest larger, higher-quality lung biopsy samples than conventional forceps. Such samples could prove ideal for diagnosing diffuse interstitial lung diseases (DILD). We compared the safety and efficacy of transbronchial biopsy with cryoprobe and conventional-forceps sampling of the lung.   Patients and methods:  This randomised clinical trial analysed data for 77 patients undergoing transbronchial lung biopsy for evaluation of DILD; patients were assigned to either a conventional-forceps group or a cryoprobe group. Two blinded pathologists assessed the tissue samples and agreed on histologic diagnoses. We recorded the duration of procedures, complications and sample-quality variables.   Results:  The mean area of tissue samples harvested by cryoprobe and conventional forceps, respectively, were 14.7 ± 11 mm 2  and 3.3 ± 4.1 mm 2  (p   The pathologists reached a histologic diagnosis in more cases in the cryoprobe group (74.4.%) than in the conventional-forceps group (34.2%) (p   Nonsignificantly more moderate bleeding occurred in the cryoprobe group (56.4%  versus  34.2% in the conventional-forceps group). Pneumothorax was also slightly more common in the cryoprobe group (7.7%  versus  5.2%).   Conclusions:  Transbronchial cryobiopsy is a new bronchoscopic technique that may prove useful in the diagnosis of DILD.
The Relationship between Individual Histologic Features and Disease Progression in Idiopathic Pulmonary Fibrosis
Authors: Andrew G. Nicholson, Laura G. Fulford, Thomas V. Colby, Roland M. du Bois, David M. Hansell, Athol U. Wells
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

We have retrospectively studied 53 patients with idiopathic pulmonary fibrosis and a histologic diagnosis of usual interstitial pneumonia and evaluated the prognostic significance of four individual histologic features (fibroblastic foci [FF], interstitial mononuclear cell infiltrate, established fibrosis, and intra-alveolar macrophages) using a semiquantitative scale of 0-6. An objective count of FF was also undertaken. Using weighted kappa coefficients, interobserver agreement between pathologists was moderate to good (0.56-0.76). Subjective and objective FF scores were strongly associated (R(S) = 0.88, < 0.00005). Mortality was independently linked to a high FF score, p = 0.006, and a low percent predicted carbon monoxide diffusing capacity (DL(CO)), p = 0.01. For pulmonary function, on univariate analysis, the strongest correlations were observed between increasing interstitial mononuclear cell infiltrate or FF scores and greater declines in forced vital capacity (FVC) or DL(CO) at 6 months. Multivariate models revealed that increasing FF scores were independently associated with greater declines in FVC and DL(CO) at both 6 and 12 months. Increasing interstitial mononuclear cell infiltrate scores were also independently linked to functional decline, but only at 6 months. These data suggest a reproducible method on biopsy for predicting rate of disease progression in patients with idiopathic pulmonary fibrosis.
Anal cancer: Current standards in care and recent changes in practice
Authors: Ravi Shridhar, David Shibata, Emily Chan, Charles R. Thomas
Journal: CA A Cancer Journal for Clinicians (2015)

Abstract Answer questions and earn CME/CNE The management of squamous cell carcinomas of the anal canal has evolved from surgery as first‐line treatment to curative chemoradiation, with surgery reserved for salvage. Significant progress has been made in understanding how to most effectively deliver chemotherapy and reduce toxicity through advancements in radiation delivery. The purpose of this article is to review the multimodality approach to the diagnosis and management of anal cancer based on a review of the published data and in light of available guidelines. CA Cancer J Clin 2015;65: 139–162. © 2015 American Cancer Society.
The Myxoma Poxvirus Protein, M11L, Prevents Apoptosis by Direct Interaction with the Mitochondrial Permeability Transition Pore
Authors: Helen Everett, Michele Barry, Xuejun Sun, Siow Fong Lee, Christine Frantz, Luc G. Berthiaume, Grant McFadden, R. Chris Bleackley
Journal: The Journal of Experimental Medicine (2002)

M11L, an antiapoptotic protein essential for the virulence of the myxoma poxvirus, is targeted to mitochondria and prevents the loss of mitochondrial membrane potential that accompanies cell death. In this study we show, using a cross-linking approach, that M11L physically associates with the mitochondrial peripheral benzodiazepine receptor (PBR) component of the permeability transition (PT) pore. Close association of M11L and the PBR is also indicated by fluorescence resonance energy transfer (FRET) analysis. Stable expression of M11L prevents the release of mitochondrial cytochrome c induced by staurosporine or protoporphyrin IX (PPIX), a ligand of the PBR. Transiently expressed M11L also prevents mitochondrial membrane potential loss induced by PPIX, or induced by staurosporine in combination with PK11195, another ligand of the PBR. Myxoma virus infection and the associated expression of early proteins, including M11L, protects cells from staurosporine- and Fas-mediated mitochondrial membrane potential loss and this effect is augmented by the presence of PBR. We conclude that M11L regulates the mitochondrial permeability transition pore complex, most likely by direct modulation of the PBR.
What are minimal important changes for asthma measures in a clinical trial?
Authors: N.c Santanello, J Zhang, B Seidenberg, T.f Reiss, B.l Barber
Journal: European Respiratory Journal (1999)

In this study, the perceptions of asthmatics to change in their disease was associated with observed changes in clinical asthma measures, in order to identify the threshold where changes in clinical asthma measures are perceivable by patients. The study included 281 asthmatic patients, aged 18-63 yrs, in a randomized, placebo-controlled clinical trial of a leukotriene antagonist. Changes were related in: 1) asthma symptom scores; 2) inhaled beta-agonist use; 3) forced expiratory volume in one second (FEV1); and 4) peak expiratory flow (PEF) to a global question that queried overall change in asthma since starting the study drug. Additional analyses examined differences in the group reporting minimal improvement by treatment (active treatment versus placebo), sex and age groups. The average minimal patient perceivable improvement for each measure was: 1) -0.31 points for the symptom score on a scale of 0-6; 2) -0.81 puffs x day(-1) for inhaled beta-agonist use; 3) 0.23 L for FEV1; and 4) 18.79 L x min(-1) for PEF. In general placebo-treated patients and older patients, who reported minimal improvement, experienced less mean improvement from baseline than active-treated patients and younger patients, who reported minimal improvement. Determining the minimal patient perceivable improvement value for a measure may be helpful to interpret changes. However, interpretation should be carried out cautiously when reporting a single value as a clinically important change.
Influenza Virus Lung Infection Protects from Respiratory Syncytial Virus–Induced Immunopathology
Authors: Gerhard Walzl, Sabrina Tafuro, Paul Moss, Peter J.M. Openshaw, Tracy Hussell
Journal: The Journal of Experimental Medicine (2000)

The effect of infection history is ignored in most animal models of infectious disease. The attachment protein of respiratory syncytial virus (RSV) induces T helper cell type 2–driven pulmonary eosinophilia in mice similar to that seen in the failed infant vaccinations in the 1960s. We show that previous influenza virus infection of mice: (a) protects against weight loss, illness, and lung eosinophilia; (b) attenuates recruitment of inflammatory cells; and (c) reduces cytokine secretion caused by RSV attachment protein without affecting RSV clearance. This protective effect can be transferred via influenza-immune splenocytes to naive mice and is long lived. Previous immunity to lung infection clearly plays an important and underestimated role in subsequent vaccination and infection. The data have important implications for the timing of vaccinations in certain patient groups, and may contribute to variability in disease susceptibility observed in humans.
Circumcision of HIV-infected men and transmission of human papillomavirus to female partners: analyses of data from a randomised trial in Rakai, Uganda
Authors: Aaron AR Tobian, Xiangrong Kong, Maria J Wawer, Godfrey Kigozi, Patti E Gravitt, David Serwadda, Kevin P Eaton, Fred Nalugoda, Thomas C Quinn, Ronald H Gray
Journal: The Lancet Infectious Diseases (2011)
Evolution of host specialization in gut microbes: the bee gut as a model
Authors: Waldan K Kwong, Nancy A Moran
Journal: Gut Microbes (2015)

Bacterial symbionts of eukaryotes often give up generalist lifestyles to specialize to particular hosts. The eusocial honey bees and bumble bees harbor two such specialized gut symbionts, Snodgrassella alvi and Gilliamella apicola. Not only are these microorganisms specific to bees, but different strains of these bacteria tend to assort according to host species. By using in-vivo microbial transplant experiments, we show that the observed specificity is, at least in part, due to evolved physiological barriers that limit compatibility between a host and a potential gut colonizer. How and why such specialization occurs is largely unstudied for gut microbes, despite strong evidence that it is a general feature in many gut communities. Here, we discuss the potential factors that favor the evolution of host specialization, and the parallels that can be drawn with parasites and other symbiont systems. We also address the potential of the bee gut as a model for exploring gut community evolution.
A HIF-Regulated VHL-PTP1B-Src Signaling Axis Identifies a Therapeutic Target in Renal Cell Carcinoma
Authors: Natsuko Suwaki, Elsa Vanhecke, Katelyn M. Atkins, Manuela Graf, Katherine Swabey, Paul Huang, Peter Schraml, Holger Moch, Amy Mulick Cassidy, Daniel Brewer, Bissan Al-Lazikani, Paul Workman, Johann De-Bono, Stan B. Kaye, James Larkin, Martin. E. Gore, Charles L. Sawyers, Peter Nelson, Tomasz M. Beer, Hao Geng, Lina Gao, David Z. Qian, Joshi J. Alumkal, Gary Thomas, George V. Thomas
Journal: Science Translational Medicine (2011)

Signaling through the VHL-PTP1B-Src pathway in renal cell carcinomas may determine sensitivity to Src inhibitors and provide a basis for treatment planning.
Mitochondrial dysfunction in airway epithelium increases pro-inflammatory IL-8, impairs barrier function and reduces glucocorticoid responsiveness
Authors: Roland Hoffmann, Simone Brandenburg, Nick ten Hacken, Antoon van Oosterhout, Irene Heijink
Journal: European Respiratory Journal (2011)

Introduction: Despite the broad anti-inflammatory effects of glucocorticoids (GC), they provide little therapeutic benefit in COPD. Mitochondrial dysfunction has been described in COPD patients and can be induced in airway epithelial cells in vitro by cigarette smoke. We hypothesize that impaired mitochondrial function induces a phenotypic shift in airway epithelial cells leading to increased pro-inflammatory responses, impaired barrier function and reduced GC sensitivity.

Methods: We determined IL-8 secretion (ELISA) and epithelial barrier function (ECIS) in the alveolar epithelial cell line A549 and the mitochondrial impaired cell line A549.B2 and their sensitivity to the GC budesonide (10-8M).

Results: Basal production of IL-8 by mitochondrially impaired A549.B2 cells is increased compared to A549 control cells. Moreover, suppression of IL-8 by the GC budesonide (10-8M) is significantly less (24%±9%, p<0.02) in A549.B2 cells compared to A549 cells. Furthermore, while budesonide was able to efficiently increase barrier function in control A549 cells (p<0.001), there was not significant effect in A549.B2 cells. Finally, we observed that A549.B2 cells were less capable to recover from wounding than control A549 cells.

Conclusion/Discussion: In conclusion, our data indicate that mitochondrial dysfunction leads to increased pro-inflammatory activity, inefficient wound healing and reduced responsiveness to GCs. We speculate that mitochondrial dysfunction as observed in COPD may contribute to the GC-insensitive chronic airway inflammation in this disease.
Identification and characterization of intrahepatic hepatitis b virus dna in hbsag-seronegative patients with chronic liver disease and hepatocellular carcinoma in Taiwan
Authors: Ming-Yang Lai, Pei-Jer Chen, Pei-Ming Yang, Jin-Chuan Sheu, Juei-Low Sung, Ding-Shinn Chen
Journal: Hepatology (1990)

To clarify the role of hepatitis B virus infection in HBsAg-seronegative patients with chronic liver disease and hepatocellular carcinoma in Taiwan, we examined the hepatitis B virus DNA in liver biopsy tissues of 112 patients by Southern blot analysis. The patients studied included 43 patients with nonalcoholic chronic liver disease, 21 patients with hepatocellular carcinoma and 48 control patients with other hepatobiiary and gastrointestinal diseases. To confirm the specificity of the intrahepatic hepatitis B virus DNA signal and to understand the structure of the integrated viral sequences, molecular cloning and DNA sequencing of an integrated hepatitis B virus DNA were done in one patient. Among 13 patients without serological evidence of previous hepatitis B virus infection, no hepatitis B virus sequences were found in the liver. In other HBsAg-negative patients with evidence of previous hepatitis B virus exposure, a substantial positive rate of intrahepatic hepatitis B virus DNA was found (7%). The intrahepatic hepatitis B virus DNA was all in integrated form. The positive rate among patients with nonalcoholic chronic hepatitis and cirrhosis (2%) was not different from that of the control group with other hepatobiliary and gastrointestinal diseases (4%). However, the positive rate of integrated hepatitis B virus DNA between hepatocellular carcinoma patients and nonhepatocellular carcinoma patients was statistically significant (19% vs. 3%, p &lt;0.05). Molecular cloning and sequencing of a 3.0 kb Eco RI fragment of an integrated hepatitis B virus DNA from an anti-HBspositive patient revealed that it was a partial copy of the hepatitis B virus genome. Extensive rearrangement of the integrated viral sequences was found and might account for nonproduction of HIBsAg. We conclude that a substantial (7.8%) proportion of HBsAg-negative patients with chronic liver disease and hepatocellular carcinoma in Taiwan have hepatitis B virus DNA sequence in the liver, and integration of hepatitis B virus DNA may play a role in the development of hepatocellular carcinoma. (Hepatology 1990;12:575-581).
Possible Reasons for Drop of Resting Potential of Mammalian Heart Preparations During Hypothermia
Authors: JEAN DÉLÉZE
Journal: Circulation Research (1960)

Between 37 and 20 C., the resting potential of sheep ventricular and Purkinje fibers was found to be proportional to the absolute temperature. Prom 20 to 0 C., the potential drop was 3 times greater than that predicted from the theory of a concentration potential. Rapid heating by high-frequency current of previously cooled preparations, revealed no time lag between the rise of potential and the rise of temperature. Fibers kept in a Na-free solution still showed a large temperature sensitivity. With poisoned fibers, the resting potential was almost proportional to the absolute temperature. The results appear to contradict the hypothesis that extracellular K accumulation in the cold is the cause of the potential drop. They also exclude the hypothesis that a relative rise of the Na-inward current is the reason for depolarization. They support the idea that "active" extrusion of Na ions normally contributes to the resting potential, and that the pumping rate decreases considerably in the cold.
Hepatocellular Carcinoma Risk Factors and Disease Burden in a European Cohort: A Nested Case-Control Study
Authors: D. Trichopoulos, C. Bamia, P. Lagiou, V. Fedirko, E. Trepo, M. Jenab, T. Pischon, U. Nothlings, K. Overved, A. Tjonneland, M. Outzen, F. Clavel-Chapelon, R. Kaaks, A. Lukanova, H. Boeing, K. Aleksandrova, V. Benetou, D. Zylis, D. Palli, V. Pala, S. Panico, R. Tumino, C. Sacerdote, H. B. Bueno-De-Mesquita, H. J. Van Kranen, P. H. M. Peeters, E. Lund, J. R. Quiros, C. A. Gonzalez, M.-J. Sanchez Perez, C. Navarro, M. Dorronsoro, A. Barricarte, B. Lindkvist, S. Regner, M. Werner, G. Hallmans, K.-T. Khaw, N. Wareham, T. Key, I. Romieu, S.-C. Chuang, N. Murphy, P. Boffetta, A. Trichopoulou, E. Riboli
Journal: JNCI Journal of the National Cancer Institute (2011)

To date, no attempt has been made to systematically determine the apportionment of the hepatocellular carcinoma burden in Europe or North America among established risk factors.Using data collected from 1992 to 2006, which included 4,409,809 person-years in the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 125 case patients with hepatocellular carcinoma, of whom 115 were matched to 229 control subjects. We calculated odds ratios (ORs) for the association of documented risk factors for hepatocellular carcinoma with incidence of this disease and estimated their importance in this European cohort.Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (OR = 9.10, 95% confidence interval [CI] = 2.10 to 39.50 and OR = 13.36, 95% CI = 4.11 to 43.45, respectively), obesity (OR = 2.13, 95% CI = 1.06 to 4.29), former or current smoking (OR = 1.98, 95% CI = 0.90 to 4.39 and OR = 4.55, 95% CI = 1.90 to 10.91, respectively), and heavy alcohol intake (OR = 1.77, 95% CI = 0.73 to 4.27) were associated with hepatocellular carcinoma. Smoking contributed to almost half of all hepatocellular carcinomas (47.6%), whereas 13.2% and 20.9% were attributable to chronic HBV and HCV infection, respectively. Obesity and heavy alcohol intake contributed 16.1% and 10.2%, respectively. Almost two-thirds (65.7%, 95% CI = 50.6% to 79.3%) of hepatocellular carcinomas can be accounted for by exposure to at least one of these documented risk factors.Smoking contributed to more hepatocellular carcinomas in this Europe-wide cohort than chronic HBV and HCV infections. Heavy alcohol consumption and obesity also contributed to sizeable fractions of this disease burden. These contributions may be underestimates because EPIC volunteers are likely to be more health conscious than the general population.
Modulation of glucocorticoid receptor expression in human bronchial epithelial cell lines by IL-1 beta, TNF-alpha and LPS
Authors: MM Verheggen, PT van Hal, PW Adriaansen-Soeting, BJ Goense, HC Hoogsteden, AO Brinkmann, MA Versnel
Journal: European Respiratory Journal (1996)

Bronchial epithelium plays a major role in the regulation of inflammatory reactions in the airways. It is thought to be a possible target for glucocorticoid therapy. Glucocorticoid responsiveness requires the presence of specific glucocorticoid receptors (GR). Until now, little was known about the presence of such receptors in the human bronchial epithelium. In this study we demonstrated the expression of GR messenger ribonucleic acid (mRNA) in two simian virus (SV)-40/adenovirus-transformed human bronchial epithelial cell lines, BEAS S6 and BEAS 2B. In a whole cell dexamethasone binding assay, BEAS S6 and BEAS 2B cells were found to possess (mean +/- SEM) 28.9 +/- 4.4 x 10(3) and 32.1 +/- 5.7 x 10(3) binding sites per cell, respectively, with dissociation constant (Kd) values of 8.2 +/- 1.5 and 8.6 +/- 2.4 nM, respectively. Using electrophoretic mobility shift assays we demonstrated the binding of nuclear translocated GR to specific sites on deoxyribonucleic acid (DNA), named glucocorticoid responsive elements (GRE). Lipopolysaccharide (LPS) and interleukin-1 beta (IL-1 beta) significantly increased the number of GR per cell (median = 312% and 171% of control, respectively; p &lt; 0.05), but significantly reduced the ligand affinity of these receptors, i.e. increased the Kd (median = 410% and 145% of control, respectively; p &lt; 0.05) in BEAS 2B cells. These results indicate that the bronchial epithelium may be an actual target for glucocorticoid therapy. Inflammatory mediators, such as IL-1 beta and LPS, modulate the number and ligand affinity of these GR. Therefore, the response of bronchial epithelium to glucocorticoid therapy may be modulated by airway diseases associated with inflammation.
Mitofusin 2 Triggers Vascular Smooth Muscle Cell Apoptosis via Mitochondrial Death Pathway
Authors: Xiaomei Guo, Kuang-Hueih Chen, Yanhong Guo, Hua Liao, Jian Tang, Rui-Ping Xiao
Journal: Circulation Research (2007)

Previous studies have shown that mitofusin 2 ( Mfn-2 ) (or hyperplasia suppressor gene [ HSG ]) inhibits vascular smooth muscle cell (VSMC) proliferation. Here, we demonstrate that Mfn-2 is a primary determinant of VSMC apoptosis. First, oxidative stress with H 2 O 2 , inhibition of protein kinase C with staurosporine, activation of protein kinase A with forskolin, and serum deprivation concurrently elevate Mfn-2 expression and induce VSMC apoptosis. Second, overexpression of Mfn-2 also triggers apoptosis of VSMCs in culture and in balloon-injured rat carotid arteries, thus contributing to Mfn-2–mediated prevention of neointima formation after angioplasty. Third, Mfn-2 silencing protects VSMCs against H 2 O 2 or Mfn-2 overexpression–induced apoptosis, indicating that upregulation of Mfn-2 is necessary and sufficient for oxidative stress–mediated VSMC apoptosis. The Mfn-2 proapoptotic effect is independent of its role in mitochondrial fusion but mainly mediated by inhibition of Akt signaling and the resultant activation of the mitochondrial apoptotic pathway, as manifested by decreased Akt phosphorylation, increased mitochondrial Bax/Bcl-2 ratio, cytochrome c release, and activation of caspases-9 and caspase-3. Furthermore, Mfn-2–induced apoptosis was blocked by overexpression of an active phosphoinositide 3-kinase mutant or Bcl-xL or inhibition of caspase-9 but not caspases-8. Thus, in addition to its antiproliferative effects, Mfn-2 constitutes a primary determinant of VSMC apoptosis.
Transient oxygen uptake in trained children at the onset of maximal arm and leg exercise
Authors: N. Armstrong, B. Davies, J. Mulhall
Journal: British Journal of Sports Medicine (1982)

remained relatively constant.Wide variations in white cell count were observed during the study in both the swimmers and control groups.These results were discussed in relation to various factors, including physical training, which may alter the concentrations of cellular components in the peripheral blood, either through altering the plasma volume and/or by altering the total red cell population.