tbuckley/cabot-search huggingface dataset:
Inducible nitric oxide synthase as a predictor for progression to lung cancer in patients with bronchial squamous dysplasia, a per patient analysis
Authors: Alaa Mohamed, Kiyoshi Shibuya, Ichiro Yoshino, Yukio Nakatani
Journal: European Respiratory Journal (2012)

Background: This study addressed the immunohistochemical (IHC) expression of iNOS, as a predictor for progression of bronchial Squamous Dysplasia (SD) to lung cancer(LC).

Methods: A total of 114 patients (111 men and 3 women) with at least 1 bronchial SD, at least 1 follow-up evaluation and normal baseline chest computed tomography (CT) were evaluated. Median age was 68 years (range,44–84 yr) and median follow-up duration was 21 months (range,4-98 months). Follow-up included periodic white light and autofluorescence bronchoscopy and chest CT. Expression of iNOS (inducible nitric oxide synthase) in bronchial epithelium biopsy specimens was evaluated by immunohistochemistry (IHC).Diagnosis of carcinoma in situ (CIS) and/or LC were follow-up endpoints.

Results: On follow-up CIS or LC were detected in 16% of patients. Progression to CIS or LC occurred more frequently in patients with, positive iNOS (p<0.001) IHC expression, COPD (p=0.012), positive and baseline high grade SD (p=0.035). Multivariate analysis showed that risk for progression was closely related to iNOS expression (RR=10.521; 95% CI=2.75-40.3; p=0.001) and airflow obstruction (RR=0.959;95% CI=0.923-0.997; p=0.044).The positive and negative predictive values iNOS were 48% and 95%,respectively.

Conclusion : In patients with bronchial SD, iNOS IHC expression and airflow limitation are independent risk factor for progression to CIS or LC. This study supports the hypothesis that inflammation and oxidative stress promote lung carcinogenesis.
Can physical activity level to be associated with complications after abdominal surgery? A preliminary bicentric study
Authors: Fernando Wegner, Daniel Souza, Luciana Chiavegato, Adriana Lunardi
Journal: European Respiratory Journal (2014)

Although guidelines on surgical risk consider performance status as a predictor of postoperative complications (PC), this assessment is based on patients9 subjective reports or on expensive and not easily accessible tests such as the cardiopulmonary test.  Objectives:  to measure physical activity levels using accelerometry as a predictor of postoperative complications after abdominal surgery.  Methods:  This prospective study enrolled 76 candidates (61% female, 50.6±16.1yrs, 29.1±6.7Kg/m 2 , 24% cancer) for elective abdominal surgery from two university hospitals. The physical activity was assessed by Actigraph GTX3 on waist of patients during the 4 consecutive days on preoperative period. Pulmonary, cardiac, and thromboembolic complications were analysed postoperatively until discharge by a blinded researcher. Logistic regression was used to test the predictive power of the physical activity level for PC following abdominal surgery.  Results:  PC was developed in 10.5% (n=8) of the patients (6 pulmonary, 1 cardiac, 1 leg thromboembolism). Length of time in vigorous physical activity (>5725 moviments) 1  in the preoperative period tends to be negatively related to PC (R 2 =0.40; p=0.06). There was no association of length of time in physical inactivity ( 1  with PC (p>0.05).  Conclusion : Our preliminary results show that vigorous physical activity may be protective for complications after elective abdominal surgery.  1. FREEDSON PS, MELANSON E, SIRARD J. Calibration of the Computer Science and Applications, Inc. accelerometer. Med Sci Sports Exerc. 1998;30(5):777-81.
Membrane-Type 1 Matrix Metalloproteinase Expression Is Regulated by Zonula Occludens-1 in Human Breast Cancer Cells
Authors: Myriam Polette, Christine Gilles, Béatrice Nawrocki-Raby, Jouko Lohi, Walter Hunziker, Jean-Michel Foidart, Philippe Birembaut
Journal: Cancer Research (2005)

Abstract The acquisition of a migratory/invasive phenotype by tumor cells is characterized by the loss of cell-cell adhesion contacts and the expression of degradative properties. In this study, we examined the effect of the disorganization of occludin/zonula occludens (ZO)-1 tight junction (TJ) complexes on the expression of membrane-type 1 matrix metalloproteinase (MT1-MMP). We first compared the expression of MT1-MMP and the localization of occludin/ZO-1 complexes in breast tumor cell lines displaying various degrees of invasiveness. We showed that the expression of MT1-MMP in invasive breast tumor cell lines correlates with the absence of occludin and with a cytoplasmic localization of ZO-1. In contrast, noninvasive cell lines displayed a membrane staining for both ZO-1 and occludin and did not express MT1-MMP. In vivo, cytoplasmic ZO-1 and MT1-MMP could be detected in invasive tumor clusters of human breast carcinomas. We then used RNA interference strategy to inhibit ZO-1 expression in invasive BT549 cells and to evaluate the effect of ZO-1 down-regulation on MT1-MMP expression. We observed that ZO-1 small interfering RNA transfection down-regulates MT1-MMP mRNAs and proteins and subsequently decreases the ability of tumor cells to invade a reconstituted basement membrane in a Boyden chamber assay. Inversely, transfection of expression vectors encoding wild-type ZO-1 or the NH2-terminal fragment of ZO-1 comprising the PSD95/DLG/ZO-1 domains in BT549 activated a human MT1-MMP promoter luciferase reporter construct and increased cell invasiveness. Such transfections concomitantly activated the β-catenin/TCF/LEF pathway. Our results therefore show that ZO-1, besides its structural role in TJ assembly, can intervene in signaling events promoting tumor cell invasion.
The Yin and Yang of Cystic Fibrosis Transmembrane Conductance Regulator Function
Authors: Neeraj Vij, Gregory P. Downey
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is a cAMP-activated anion channel, primarily expressed in ciliated epithelial cells that have an endoluminal lining of mucus. Genetic mutations in CFTR are known to induce its peripheral and/or endoplasmic reticulum–associated degradation affecting its cell surface expression and/or stability, resulting in the pathological manifestations of CF lung disease, including hypohydration and increased viscosity of mucus, predisposing affected individuals to recurrent infections. Recent studies have identified low levels of CFTR expression in inflammatory cells such as T cells, neutrophils, and macrophages (1–3), suggesting an additional role for CFTR in the pathogenesis of chronic inflammatory CF lung disease. CFTR has also been suggested to mediate internalization and phagocytosis (4, 5) of Pseudomonas aeruginosa (Pa), a common CF pathogen. A recent study suggests that a bacterial toxin, Cif (PA2934) secreted in outer membrane vesicles by Pa, reduces CFTR-mediated chloride secretion by human airway epithelial cells (6). In this issue of the Journal, Le Gars and colleagues (pp. 170–179) describe a novel mechanism for proteolytic cleavage of CFTR that disables the channel function (7).
Seven day working: why the health secretary’s proposal is not as simple as it sounds
Authors: Helen Crump
Journal: BMJ (2015)

Health Secretary Jeremy Hunt's recent declaration that he wants to see most hospital doctors on "seven day contracts" to enable weekend working provoked the ire of many NHS staff, who have been using the Twitter hashtag #iminworkjeremy to show they already work at weekends. <b>Helen Crump</b> explores the evidence behind the proposal and its financial implications
Atopy is a risk factor for adult asthma in two rural communities in south western Nigeria
Authors: Olusoji Ige, A. Goke Falade, Ganiyu Arinola
Journal: European Respiratory Journal (2011)

Rationale:  Factors affecting asthma course are not clearly elucidated in rural communities in developing countries. Furthermore, the interaction between factors such as atopy, environmental exposure, and urbanization and helminthic infections in modulating asthma have not been well investigated.   Objectives:  To determine factors which affect asthma in adults being evaluated at 2 rural health centers in Southwest, Nigeria.   Methods:  A random sample of 31 (10M, 21F) consecutive patients with stable physician diagnosed asthma, and 29 (13M, 16F) age matched control subjects without asthma seen at the outpatient clinics in Eruwa and Igbo-Ora were enrolled into the study. All subjects completed an asthma questionnaire, underwent evaluation, which included blood tests for eosinophil, serum IgE, allergy skin test to 8 common environmental allergens, stool for ova and parasites and spirometry. Wilcoxon sign-rank tests were used to compare eosinophil counts, percentage eosinophil and allergy skin test between the groups.   Results:  Asthmatics had significantly more positive skin reaction to house dust mite, cockroach, mould, and mouse epithelium than controls (P  Total serum IgE was also significantly higher in asthmatics than in controls (mean 380 vs.194 IU/ml; P   Conclusion:  Atopy is an important factor in the expression of adult asthma in 2 rural communities of a developing country such as Nigeria where atopy is expected to be uncommon. Additional studies to evaluate rural urban dichotomy in the expression of asthma are needed.
Abstract 16917: Acute Consumption of Different Types of Oil Affects Significantly Proinflammatory Cytokines and Adhesion Molecules in Healthy Individuals
Authors: Anastasios Giolis, Dimitris Tousoulis, Nikolaos Papageorgiou, Theodora Psaltopoulou, Antigoni Miliou, Charalambos Antoniades, Pavlos Stougianos, Ioannis Ntarladimas, Charalambos Vlachopoulos, Costas Tentolouris, Athanasios Trikas, Christodoulos Stefanadis
Journal: Circulation (2010)

Background: Inter-cellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and tumor necrosis factor alpha (TNF-a) are implicated in the pathogenesis of atherosclerosis. Ho...
Conventional vs ultrathin bronchoscopy in the diagnosis of solitary pulmonary nodules (SPN)
Authors: Juan Antonio Botero Zaccour, Antoni Rosell Gratacos, Noelia Cubero de Frutos, Rosa Lopez Lisbona, Rachid Tazi Mezalek
Journal: European Respiratory Journal (2013)

PURPOSE: Ultrathin bronchoscopes can be guided under fluoroscopy to reach solitary pulmonary nodules. The aim of this study is to compare this diagnostic yield against conventional bronchoscope.

MATERIAL AND METHOD: two centers have prospectively collected patients referred to study solitary pulmonary nodules by bronchoscopy under fluoroscopy guidance. One centre performed the procedures with a conventional bronchoscope (Olympus BF Q-180, outer diameter 5.5 mm) and the other an ultrathin (Olympus XP 160, outer diameter 2.8). In both groups bronchial washings were routinely collected. In the conventional group, brushing was always performed. In the ultrathin bronchoscope group, biopsies were only performed when an endoluminal lesion was seen; if not, then bronchial brushing was performed.

RESULTS: Groups were similar in the main variables, except for the number of brushes performed, conventional group (total 31 vs. 66; p <0.05)).

Conventional (n=27): age 67.6; diameter 20.1 (SD 5.9); SUVm (n=20) 9.1; localization 0% (inner), 50% (middle), 50% (outer); bronchus sign (45%); visualized by fluoro (88.9%); biopsy performed (40.9%); brushes (2 in 55%, 3 in 44.4%). Ultrathin (n=39): age 66.9; diameter 21.5 (SD 6.0); SUVm (n=32) 7.7; localization 11.1 (inner), 55.6% (middle), 33.3% (outer); bronchus sign (68.4%); visualized by fluoro (69.2%); biopsy performed (59.1%); brushes (non2 20%, 1 in 69.2%, 2 in 7.5%%, 3 in 2.6%). The final diagnosis were achieved in 44.4% in the conventional group vs. 38.5% in the ultrathin group (p=0.6)

CONCLUSIONS: the ultrathin bronchoscope is equally effective as the conventional bronchoscopy under fluoroscopy guidance in the diagnosis of SPN.
Benzo[a]pyrene-induced CYP1A1 expression in MCF-7 cells is S-phase dependent.
Authors: Francis L. Martin
Journal: Cancer Research (2006)

5219  Xenobiotic biotransformation is often facilitated by oxidative metabolism via the cytochrome P450 (CYP) mixed function oxidase system. The aromatic hydrocarbon receptor (AhR) is a ligand-activated transcription factor that may bind benzo[a]pyrene (B[a]P). Unbound AhR resides in the cytosol as a multiprotein complex with two heat shock protein 90 molecules and an immunophilin-like molecule. When bound, the ligand-receptor complex translocates into the nucleus where the AhR dissociates from the complex and binds to a nuclear protein Arnt (AhR nuclear translocator). The resulting heterodimer binds to dioxin responsive elements and elevates the transcription of various genes, including CYP1A1, CYP1A2 and CYP1B1. In order to examine the role of cell-cycle phase on CYP up-regulation, MCF-7 cells in a confluent state (G1-phase concentrated), in an exponential growth-phase (S-phase concentrated), or following 18-h exposure of an exponentially-growing culture to 0.4 μg/ml nocodozole (G2/M-phase concentrated) were exposed to 24-h B[a]P (0.5 μM) treatment. The quantitative gene expression of CDKN1A (P21WAF1/CIP1), BCL-2, BAX, CYP1A1, CYP1A2, and CYP1B1 was determined. In G1-phase concentrated and/or G2/M-phase concentrated cultures, B[a]P-induced up-regulation of CYP1A1 was markedly suppressed (maximum ≈30-fold elevations compared to control calibrator) following 24-h exposures compared to ≈150-fold elevations observed in S-phase concentrated cultures. Although not as marked, a similar profile of differential gene expression modulated by cell-cycle phase was observed with CYP1A2 and CYP1B1. Consistent with this finding, S-phase concentrated cultures exhibited up-regulated P21WAF1/CIP1 (≈20-fold), down-regulated BCL-2 (≈5-fold), and up-regulated BAX (≈2-fold); suggesting a marked reduction in B[a]P-damage induction, these effects were not observed in G1-phase concentrated and/or G2/M-phase concentrated cultures. AhR influences G1-phase progression through interaction with retinoblastoma protein and up-regulated AhR-dependent activation of CYP1A1 appears to be cell-cycle phase dependent. Interestingly, exposure to relatively non-cytotoxic B[a]P concentrations results in cells accumulating in S-phase suggesting that evasion of G1-phase arrest is a factor to the transforming activity of DNA-adduct-forming carcinogens. Although hormone-induced effects mediated via the oestrogen receptors ERα and ERβ (e.g. AhR-ER crosstalk) undoubtedly play an important role in the proliferative response, such observations that CYP1A1 may play a pivotal role in G1- to S-phase transition might suggest that in combination with characteristic genetic toxicological effects, exogenous ligands of the AhR, through disrupted cell cycle kinetics, could drive the clonal expansion of an initiated phenotype.
Epitope specificity determines cross‐protection of a <scp>SIT</scp>‐induced IgG<sub>4</sub> antibody
Authors: E. Gadermaier, L. K. James, M. H. Shamji, K. Blatt, K. Fauland, P. Zieglmayer, T. Garmatiuk, M. Focke‐Tejkl, M. Villalba, R. Beavil, W. Keller, P. Valent, S. R. Durham, H. J. Gould, S. Flicker, R. Valenta
Journal: Allergy (2015)

The calcium-binding 2EF-hand protein Phl p 7 from timothy grass pollen is a highly cross-reactive pollen pan-allergen that can induce severe clinical symptoms in allergic patients. Recently, a human monoclonal Phl p 7-specific IgG4 antibody (mAb102.1F10) was isolated from a patient who had received grass pollen-specific immunotherapy (SIT).We studied epitope specificity, cross-reactivity, affinity and cross-protection of mAb102.1F10 towards homologous calcium-binding pollen allergens. Sequence comparisons and molecular modelling studies were performed with ClustalW and SPADE, respectively. Surface plasmon resonance measurements were made with purified recombinant allergens. Binding and cross-reactivity of patients' IgE and mAb102.1F10 to calcium-binding allergens and peptides thereof were studied with quantitative RAST-based methods, in ELISA, basophil activation and IgE-facilitated allergen presentation experiments.Allergens from timothy grass (Phl p 7), alder (Aln g 4), birch (Bet v 4), turnip rape (Bra r 1), lamb's quarter (Che a 3) and olive (Ole e 3, Ole e 8) showed high sequence similarity and cross-reacted with allergic patients' IgE. mAb102.1F10 bound the C-terminal portion of Phl p 7 in a calcium-dependent manner. It cross-reacted with high affinity with Ole e 3, whereas binding and affinity to the other allergens were low. mAb102.1F10 showed limited cross-inhibition of patients' IgE binding and basophil activation. Sequence comparison and surface exposure calculations identified three amino acids likely to be responsible for limited cross-reactivity.Our results demonstrate that a small number of amino acid differences among cross-reactive allergens can reduce the affinity of binding by a SIT-induced IgG and thus limit cross-protection.
The preparation and testing of the proposed International Reference (IRP) Bermuda grass ()-pollen extract
Authors: H. Baer, M.C. Anderson, R.M. Helm, J.W. Yunginger, H. Lowenstein, B. Gjesing, William White, Geraldine Douglass, P.Reiman Phillips, M. Schumacher, B. Hewitt, B.G. Guerin, J. Charpin, J. Carreira, M. Lombardero, A.K.M. Ekramoddoullah, F. Kisil, R. Einarsson
Journal: Journal of Allergy and Clinical Immunology (1986)
Secretory Leukocyte Protease Inhibitor
Authors: Sonia A. Gomez, Claudia L. Argüelles, Diego Guerrieri, Nancy L. Tateosian, Nicolás O. Amiano, Rut Slimovich, Paulo C. Maffia, Eduardo Abbate, Rosa M. Musella, Verónica E. Garcia, H. Eduardo Chuluyan
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Human secretory leukocyte protease inhibitor (SLPI) displays bactericidal activity against pathogens such as Escherichia coli and Streptococcus. Furthermore, it has been reported that murine SLPI shows potent antimycobacterial activity.Objectives: The aim of the present study was to investigate whether human recombinant SLPI not only kills mycobacteria but also acts as a pattern recognition receptor for the host immune system.Methods: For the in vivo experiment, BALB/c mice were infected by intranasal instillation with Mycobacterium bovis BCG and viable BCG load in lung homogenates was later determined. For the in vitro experiments, SLPI was incubated overnight with a suspension of M. bovis BCG or the virulent strain Mycobacterium tuberculosis H37Rv, and the percentage survival as well as the binding of SLPI to mycobacteria was determined. Furthermore, bacteria phagocytosis was also determined by flow cytometry.Measurements and Main Results: Intranasal SLPI treatment decreased the number of colony-forming units recovered from lung homogenates, indicating that SLPI interfered with M. bovis BCG infection. Moreover, SLPI decreased the viability of both M. bovis BCG and H37Rv. We demonstrated that SLPI attached to the surface of the mycobacteria by binding to pathogen-associated molecular pattern mannan-capped lipoarabinomannans and phosphatidylinositol mannoside. Furthermore, we found that in the sputum of patients with tuberculosis, mycobacteria were coated with endogenous SLPI. Finally, we showed that phagocytosis of SLPI-coated mycobacteria was faster than that of uncoated bacteria.Conclusions: The present results demonstrate for the first time that human SLPI kills mycobacteria and is a new pattern recognition receptor for them.
Inhibition of Spleen Tyrosine Kinase Potentiates Paclitaxel-Induced Cytotoxicity in Ovarian Cancer Cells by Stabilizing Microtubules
Authors: Yu Yu, Stephanie Gaillard, Jude M. Phillip, Tai-Chung Huang, Sneha M. Pinto, Nayara G. Tessarollo, Zhen Zhang, Akhilesh Pandey, Denis Wirtz, Ayse Ayhan, Ben Davidson, Tian-Li Wang, Ie-Ming Shih
Journal: Cancer Cell (2015)
Intussusception of Invaginated Meckel's Diverticulum
Authors: R C N Williamson, M J Cooper, W E G Thomas
Journal: Journal of the Royal Society of Medicine (1984)

Two middle-aged patients are reported who came to laparotomy with a presumptive diagnosis of small bowel tumour. There was no overt evidence of small bowel obstruction in either case. They were found at laparotomy to have intussusception of an invaginated Meckel's diverticulum. This condition should be considered in the differential diagnosis of ileal tumours.
Abstract 846: Chronic Cardiac Resynchronization Reverses Abnormal Calcium Handling in Failing Ventricular Myocytes
Authors: Serge Viatchenko-Karpinski, Dmitry Terentyev, Zuzana Kubalova, Andriy Belevych, Yoshinori Nishijima, Arun Sridhar, Inna Gyorke, Radmila Terentyeva, Daise N da Cunha, John D Bonagura, David S Feldman, Robert L Hamlinl, Cynthia A Carnes, Sandor Gyorke
Journal: Circulation (2006)

Cardiac resynchronization therapy (CRT) represents a promising treatment modality to alleviate LV dysfunction in humans with heart failure (HF). The underlying mechanisms contributing to improved c...
Management: Part III—Surgery
Authors: John G Kral
Journal: BMJ (2006)

professor of surgery and medicine in the department of surgery, SUNY Downstate Medical Center, New York.

Although surgery can be a potentially life extending treatment for obesity, most patients and doctors reject surgical intervention. Moreover, no national health budget or insurance can afford surgery on a very large scale. However, obesity surgery is a successful, validated, legitimate treatment and needs to be considered in some circumstances.

Healthcare workers and the public alike still lack awareness about the epidemiological consequences of and the severity of outcomes associated with pregnancy in obese women. Outcomes include fetal loss, malformations, intellectual impairment, lifelong psychosocial suffering, and programming of chronic metabolic diseases. People also lack awareness about the epigenetic transmission of obesity to their daughters, who themselves go on to become obese mothers.

View this table:

Goal and methods of obesity surgery 



Given the seriousness of the obesity epidemic, “preventive surgery” in obese young women may therefore be indicated when all else fails. Furthermore, such surgery can prevent the inexorable progression of obesity towards manifest comorbidity (such as diabetes, congestive heart failure, liver cirrhosis, and hypertension) and, ultimately, irreversible chronic disease and end organ failure.

View this table:

Key prerequisites for obesity surgery



Obesity surgery entails a trade-off between the progressively debilitating intractable symptoms and chronic diseases associated with obesity and the side effects and complications of operations designed to create chronic (relative) undernutrition. Most obese adults who have chosen surgery and had complications (including death) have been satisfied with their choice because their lives as obese individuals were often not worth living.

Early obesity surgery can bring secondary health problems. Nevertheless, the extraordinary lifelong suffering imposed by the psychosocial sequelae of extreme childhood obesity cannot be underestimated: depression, anxiety, eating disorders, vocational and marital failure, and years of life lost. Mitigating the impairment of quality of life might well be …