tbuckley/cabot-search huggingface dataset:
HMGB1 expression and function in the allergic airway immune response
Authors: Zaridatul Aini Ibrahim, Sharon Wong, Simon Phipps, Carol Armour, Maria Sukkar
Journal: European Respiratory Journal (2014)

We have identified a critical role for high-mobility group box-1 (HMGB1) in the allergic airway immune response in mouse models of asthma (Ullah et al JACI 2014). Within 24hrs of house dust mite (HDM) inhalation, airway epithelial cells (AECs) mobilise HMGB1 from the nuclear to cytoplasmic compartment. Accumulation of HMGB1 in BALF suggests it is actively secreted by AECs, while presence of HMGB1/IL-1α complexes in BALF suggests these molecules act in concert. In this study, we investigated expression and function of HMGB1/IL-1α in allergen exposed human AECs  in vitro .   Methods:  Primary human AECs or 16-HBE cells in monolayer culture were stimulated with HDM or cockroach (CR) extracts in the presence/absence of protease inhibitors. The effect of HMGB1 (1-10µg/mL) and IL-1α (1ng/mL) on epithelial cell function was also studied.   Results:  HDM and CR induced IL-1α release, and this was protease dependent. Interestingly, while HDM and CR induced HMGB1 nuclear to cytoplasmic translocation, they did not induce its extracellular release. AECs stimulated with IL-1α or HMGB1 produced several cytokines (GM-CSF, IL-6 and CCL-20), although IL-33 or TSLP production was not detected. When in complex with IL-1α, HMGB1 potentiated IL-6 release. HMGB1 and IL-1α alone or in complex did not modulate E-cadherin expression.   Conclusion:  Failure to detect HMGB1 secretion in AECs  in vitro  suggests that AECs may not be the source of extracellular HMGB1  in vivo , or that additional factors are required for its extracellular release. Further elucidation of the factors regulating HMGB1/IL-1α secretion in AECs, and the modulatory effects of HMGB1/IL-1α on AEC function is likely to expose new strategies for the primary prevention of asthma.
Fixed airflow obstruction in asthma is related to systemic eosinophilic inflammation - Results from the Swedish GA2LEN survey
Authors: Andrei Malinovschi, Christer Janson, Karl Franklin, Bertil Forsberg, Roelinde Middelveld, Gunilla Hedlin, Sven-Erik Dahlén, Kjell Alving
Journal: European Respiratory Journal (2012)

Background: Patients with asthma and fixed airflow obstruction represent a difficult-to-treat subgroup. Increased local airways inflammation has been linked to fixed airflow obstruction, but few studies have analysed the relation to systemic eosinophilic inflammation, a component not reached by inhaled corticosteroids.

Methods: Non-smoking healthy subjects (n=130) and non-smoking asthma subjects (n=357), aged 17-76 years performed lung function, exhaled NO (FeNO) and urine eosinophil protein X (uEPX) measurements. Fixed airflow obstruction was defined as postbronchodilator FEV1/FVC under the lower limit of normality (Hankinson et al. AJRCCM 1999).

Results: Asthmatic subjects with fixed airflow obstruction (n=56) had higher uEPX levels than asthmatics without fixed airflow obstruction (n=301) ((62.4 ng/mL (51.9, 75.1)) vs. 47.2 (44.1, 50.6)) or healthy controls (40.0 (36.2, 44.2)) (geometric mean (95%CI)) (all p-values<0.05). No differences (p=0.32) were found between asthmatic subjects with or without fixed airflow obstruction in terms of FeNO, whereas both asthma groups had higher levels than controls (p<0.01). Increased levels of uEPX (p=0.04), use of inhaled corticosteroids (p=0.01) and increased age (p=0.05) were independently related to persistent airflow obstruction in asthmatics, after adjustments for study centre, height, atopy, sinusitis, rhinitis and time of day for measurements.

Conclusion: Persistent airflow obstruction in asthma was accompanied by increased urinary excretion of EPX. Further studies are warranted to investigate if more aggressive treatment of the systemic inflammation may be required to prevent fixed airflow obstruction.
Is cough with high frequency chest wall oscillation (HFCWO) effective on the differences of mucus rheological property, driving pressure?
Authors: Tetsuo Miyagawa, Tomomi Ichiba, Masayuki Takahashi
Journal: European Respiratory Journal (2013)

Background:HFCWO is commonly used for airway clearance, and effective for moving airway secretions from peripheral airway. We already reported that effects of mucus clearance on the differences of rheological property, driving pressure and frequency during HFCWO in ERS Congress 2011. However the effect of cough mucus clearance on the rheological property, driving pressure during HFCWO is not clear. The purpose of this study is to clarify differences of airway clearance efficacy in mechanically assisted cough by HFCWO.  Method:  20 normal subjects participated in this study. Mucus stimulants (MS) were prepared using thickener 1, 2, 3 and 4% and the pressure controls of SmartVest TM  were driven 30, 40, 50 and 60 on the frequency 13Hz synchronized with cough. MS rheological studied were measured frequency-dependency and stress-dependency using rheometer. They were coughed into the internal diameter of 10mm, 1-meter-long tube through a mask during SmartVest TM . We measured migration length of each MS, Peak Couth Flow (PCF), PEmax and effortless breathing.  Results:  The higher setting pressure controls droved, the more PCF and PEmax increased except of 60 (p  Conclusions  The cough synchronized with driving pressure 40 and 50 using HFCWO (SmartVest TM ) is effective for mucus clearance.
Computational modeling and biological evaluation of methylated (-)-EGCG analogs
Authors: Kristin R. Landis-Piwowar, Sheng Biao Wan, Kenyon G. Daniel, Di Chen, Tak Hang Chan, Q. Ping Dou
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4897 

The anti-cancer and cancer-preventive effects of green tea and its main constituent (-)-epigallocatechin-3-gallate [(-)-EGCG] are well documented by a variety of studies, including epidemiological, cell culture, animal, and clinical. While (-)-EGCG remains the most potent polyphenol in green tea, it is particularly unstable under neutral or alkaline conditions ( i.e . physiologic pH) and may be modified by methylation, glucuronidation and sulfonation. In order to understand the significance of methylation on cancer-preventative effects of tea polyphenols, we synthesized several (-)-EGCG and (-)-ECG analogs with various number of methyl groups (mono-, di-, and tri-) attached to the B- and/or D-rings. Additionally, we synthesized putative prodrugs that contain protective peracetate groups (removable by cellular cytosolic esterases) in place of the remaining hydroxyl groups. The structure-activity relationships (SARs) were studied by both in silico computational modeling of the methylated (-)-EGCG analogs to the proteasome active site and their in vitro inhibitory potencies against a purified 20S proteasome. While the number of methyl groups was increased, a gradual decrease was observed in the probability of methylated (-)-EGCG analogs to bind in silico to the active site of the proteasome. Consistently, as the number of methyl groups increased on the (-)-EGCG molecule, the in vitro proteasome-inhibitory potencies were also decreased. When human leukemic Jurkat T cells were tested, the pro-drug of the mono-methylated (-)-EGCG analog caused greater proteasome inhibition and apoptosis than the pro-drug of the tri-methylated (-)-EGCG analog. Our data suggest that methylation of (-)-EGCG lessens its proteasome-inhibitory ability that might lead to decreased cancer preventative effects.
Prevalence of dyspepsia in COPD patients: Experience in a large Canadian cohort
Authors: Gauthier Andréanne, Chalifoux Geneviève, Poirier Claude
Journal: European Respiratory Journal (2011)

It has been shown that dyspepsia can be associated with COPD and in some cases closely linked to COPD exacerbations. The association of dyspepsia with COPD severity (FEV1, respiratory failure) and medications is not well described. The aim of this study is to evaluate the prevalence of dyspepsia in a large canadian COPD cohort and to identify risk factors.

We retrospectively reviewed files of 1247 COPD patients. We classified patients as dyspepsia-positive (D+: 513 patients or 41%) or dyspepsia-negative (D-: 734 patients or 59%). Mean age was similar in D+ and D- (71,6 y/o versus 70,2) and we found no difference in FEV1 (44,97% versus 45,07%, p>0,05). Dyspepsia was more frequent in female patients (54,4% versus 45,4%, p  1/year) was also associated with dyspepsia (80,3% versus 71,7%, p<0,001). Finally, dyspepsia was positively related to cardio-vascular and osteoporotic comorbidities (86,7% versus 68,4%, p< 0,001). No relation was found with medications use, notably inhaled corticosteroids.

Conclusion: As reported by other publications, our retrospective study noted a high prevalence of dyspepsia in COPD patients and there was no relation with disease severity (expressed by the FEV1). Female sex, frequent acute exacerbations and comorbidities appear to be associated with dyspepsia. Surprisingly, we found a negative association with smoking status. Dyspepsia treatment consequences should now be addressed closely (QOL, exacerbations, FEV1 decline).
Role of phosphatidylinositol-3-kinase (PI3K) in TGF-β-induced proliferation and differentiation of human lung fibroblasts into myofibroblasts
Authors: Enrico Conte, Mary Fruciano, Evelina Fagone, Elisa Gili, Maria Iemmolo, Nunzio Crimi, Carlo Vancheri
Journal: European Respiratory Journal (2011)

Molecular mechanisms and pathogenesis of idiopathic pulmonary fibrosis (IPF) remain unclear yet TGF-β-induced differentiation and proliferation of fibroblasts/myofibroblasts are recognized as primary events.

We investigated the role of PI3K/Akt pathway in TGF-β-induced proliferation of human lung fibroblasts and their differentiation into myofibroblasts. Moreover, we evaluated the expression of all PI3K class I p100 isoforms (α, β, δ and γ). By using selective inhibitors, we also dissected the functional role of these isoforms.

Ex-vivo human lung fibroblasts were stimulated with TGF-β in the presence or absence of PI3Ks pan-inhibitor LY294002 as well as of selective inhibitors. Cell proliferation was evaluated by cell counts and WST-1 proliferation assay. Western blot analysis and the Sircol assay were used for assessing a-Smooth Actin (SMA) expression and collagen production, respectively. RNA messenger and protein levels of p100 isoforms were evaluated by Q-RT-PCR and western blot analysis, respectively.

Here we show that LY294002 was able to abrogate the TGF-β-induced increase in cell proliferation,α-SMA expression and collagen production besides to inhibit Akt phosphorylation, thus demonstrating the central role of PI3K/Akt pathway in TGF-β-induced lung fibroblast proliferation and differentiation. Moreover, we show that PI3K p110δ and p100γ are functionally expressed in human lung fibroblasts, in addition to the ubiquitously expressed p100α and p110β. Finally, we demonstrate a major role of p110γ and p100α in the fibrotic process.

Overall, these results suggest that specific class I PI3K isoforms can be pharmacological targets in IPF.
Epithelial Characteristics of Tumor Cells in Nasopharyngeal Carcinoma Passaged in Nude Mice: Ultrastructure 2
Authors: Guy de-Thé, Michèle Vuillaume, Beppino C. Giovanella, George Klein
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Epithelial Characteristics of Tumor Cells in Nasopharyngeal Carcinoma Passaged in Nude Mice: Ultrastructure Get access Guy de-Thé, Guy de-Thé Search for other works by this author on: Oxford Academic PubMed Google Scholar Michèle Vuillaume, Michèle Vuillaume Search for other works by this author on: Oxford Academic PubMed Google Scholar Beppino C. Giovanella, Beppino C. Giovanella Search for other works by this author on: Oxford Academic PubMed Google Scholar George Klein George Klein Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 57, Issue 5, November 1976, Pages 1101–1105, https://doi.org/10.1093/jnci/57.5.1101 Published: 01 November 1976 Article history Received: 30 December 1975 Accepted: 02 April 1976 Published: 01 November 1976
A prospective randomized trial of single-agent versus combination chemotherapy in meningeal carcinomatosis.
Authors: R N Hitchins, D R Bell, R L Woods, J A Levi
Journal: Journal of Clinical Oncology (1987)

Forty-four patients with documented meningeal carcinomatosis (small-cell lung carcinoma [SCLC], 29%; breast carcinoma, 25%) were treated in a prospective randomized trial with intrathecal methotrexate (MTX) 15 mg or MTX plus cytosine arabinoside (Ara-C) 50 mg/m2. Most patients received intrathecal hydrocortisone (HC) each treatment to minimize arachnoiditis. Overall response was 55%. Seven patients achieved complete response. Response to MTX was superior to combined MTX/Ara-C, but not significantly so (61% v 45%; P greater than .10). Response was more frequent if drugs were administered via Ommaya reservoir than by lumbar puncture (65% v 48%; P greater than .10). Concurrent radiotherapy to the CNS was associated with significantly better response (73% v 35%; P less than .05). Small-cell lung carcinoma patients showed the best response (69%). Overall median survival for the whole group was 8 weeks, but responders fared better than nonresponders (median survival, 18 v 7 weeks; P less than .05). Nausea and vomiting were the most common toxicities encountered (45%), but rarely proved limiting. An unusual, previously undocumented reaction to intrathecal HC was noted. MTX is moderately effective in nonleukemic meningeal carcinomatosis, but the addition of Ara-C does not appear to improve results. Pretreatment factors did not predict outcome in this trial.
Perceived effect on shortness of breath of an acute inhalation of saline or terbutaline: variability and sensitivity of a visual analogue scale in patients with asthma or COPD
Authors: A Noseda, J Schmerber, T Prigogine, JC Yernault
Journal: European Respiratory Journal (1992)

The purpose of the study was to validate a bipolar visual analogue scale (VAS) to assess the perceived effect on shortness of breath of an acute inhalation and to search for differences in perception between asthmatics and subjects with chronic obstructive pulmonary disease (COPD). Thirty two subjects with airway obstruction and a diagnosis of either asthma (n = 16) or COPD (n = 16) received three consecutive inhalations of isotonic saline, followed by two inhalations of 400 micrograms terbutaline. Saline was perceived by asthmatics as a slight improvement: VAS (median, 95% confidence interval) 9%, 0-18% of line length. COPD subjects could be separated into two subgroups: "high perceivers" (n = 8, VAS 43%, 33-53%) and "low perceivers" (n = 8, VAS 5%, 3-7%). The median intrasubject coefficient of variation of the three post-saline VAS ratings was 19.4% (asthma), 12.5% (COPD high perceivers), and 14.5% (COPD low perceivers). After terbutaline, asthmatics had, by selection, a larger increase in forced expiratory volume in one second (FEV1) than COPD subjects. However, for other indices (expiratory specific resistance, inspiratory vital capacity and maximal inspiratory flow at 50% forced vital capacity) the changes were smaller in COPD low perceivers than in both asthmatics and COPD high perceivers. The parallel improvement in VAS was 24%, 20-39% (asthma), 15%, 6-25% (COPD high perceivers) and 1%, -1-8% (COPD low perceivers). The most sensitive index was FEV1 in asthmatics, vital capacity in COPD subjects, VAS being among the most sensitive indices in the former, but among the least sensitive in the latter. We conclude that the sensitivity of this VAS to bronchodilation is better in asthmatics than in COPD subjects. The latter can however be separated into subgroups with high and low level of perception.
Cryptorchidism, Hernia, and Cancer of the Testis 2 3
Authors: Alan S. Morrison
Journal: JNCI Journal of the National Cancer Institute (1976)

Risk of cancer of the testis was related to nondescent and hernia in a comparison of 596 testicular cancer patients and 602 unaffected men who had been in active service in the U.S. Army between 1950 and 1970. Medical histories were obtained from routine service records. Undescended testis was associated with a testicular cancer risk 8.8 times that of normal. Among cancer patients with a history of undescended testis, seminomas were nearly twice as frequent as in the remaining patients. Of 14 patients with unilateral undescended testis, 12 had the tumor on the side of the defect. Testicular cancer risk was estimated to be 2.9 times higher in men who had reported having had an inguinal hernia than in those who had not. Side of hernia and side of tumor were not associated; histologic type was not related to history of hernia.
Abstract 2636: Age-Related Triggers for Life-Threatning Arrhythmia in the Genotyped Long QT Syndrome
Authors: Tomoko Sakaguchi, Wataru Shimizu, Hideki Ito, Takashi Noda, Yoshihiro Miyamoto, Iori Nagaoka, Takashi Ashihara, Makoto Ito, Keiko Tsuji, Seiko Ohno, Takeru Makiyama, Shiro Kamakura, Minoru Horie
Journal: Circulation (2007)

OBJECTIVES We aimed to examine whether triggers for cardiac events are different depending on the age in genotyped and symptomatic long QT syndrome (LQTS) patients. BACKGROUND Patients with LQTS become symptomatic in adolescence, but some at age ≥20 y/o. It remains unknown whether clinical features of these symptomatic LQTS patients differ depending on the onset of age. METHODS Study cohort consisted of consecutive 108 symptomatic LQTS patients (34 males and 74 females from 88 families) who were identified to carry the following genotypes; LQT1 (n = 48), LQT2 (n = 52), LQT3 (n = 8). They were divided into 2 groups according to the age of their first onset of symptoms (low age &lt;20 y/o, n = 75, average age = 10 y/o, and high age ≥20 y/o, n = 33, average age = 43 y/o), and triggers of their cardiac events (ventricular tachycardia, syncope or cardiac arrest) were analyzed. We divided the triggers into 3 categories: adrenergically-mediated factors; exercise, emotional stress, loud noise and arousal, vagally-mediated factors; rest/sleep, and secondary factors; drugs, hypokalemia, and bradycardia. RESULTS Percentage of patients with family history was significantly higher in the low age group (68% vs. 39%; p = 0.005), and prevalence of females and probands were significantly higher in the high age group (60% vs. 88%; p = 0.004, 75% vs. 97%; p = 0.006, respectively). There were no significant differences in both QTc intervals (523 ± 7 ms vs. 505 ± 10; p = 0.15) and Schwartz scores (6.3 ± 0.2 vs. 5.6 ± 0.3; p = 0.06) between the 2 groups. In the low age group, 76% of the cardiac events were initiated by adrenergically-mediated factors, and 20% were vagally mediated, but none was triggered by secondary factors. In contrast, in the high age group, 48% of the cardiac events were triggered by secondary factors, 12% adrenergically-mediated, and 18% vagally-mediated factors. The prevalence of secondary factors were as follows; 0/75 [0%] in low age vs. 16/33 [48%] in high age; p &lt; 0.001. About the subdivision of secondary triggers on the genotype, hypokalemia was only observed in LQT1, drugs mainly in LQT2, and bradycardia only in LQT2. CONCLUSION Arrhythmic triggers in LQTS differ depending on the age of the patients, stressing the importance of age-related therapy for genotyped LQTS patients.
Effect of Cytosine Arabinoside and 1,3-Bis(2-Chloroethyl)-1-Nitrosourea on Hematopoietic Precursors in the Mouse
Authors: Harvey D. Preisler, Edward S. Henderson
Journal: JNCI Journal of the National Cancer Institute (1971)

The effects of cytosine arabinoside (ara-C) and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on peripheral blood leukocyte and reticulocyte levels and bone-marrow granulocyte reserve, cellularity, and colony-Forming units (CFU) were serially studied in (BALB/c ß DBA)F1 mice. Both ara-C and BCNU acutely depressed all parameters. However, whereas recovery and over-shoot in the number of CFU were noted with ara-C, recovery was delayed for 6 weeks or more with BCNU. During the recovery phase after ara-C administration, the growth fraction of CFU increased. But, during the slow recovery from BCNU toxicity, it did not increase. These results are consistent with a direct effect of BCNU on dividing and nondividing marrow stem cells.
Cryptococcus gattii sero-mating type allelic pattern determined by multiplex PCR
Authors: M Cogliati, R D'Amicis, A M Tortorano
Journal: Clinical Microbiology and Infection (2014)

Molecular methods to differentiate serotypes, mating types and molecular types of Cryptococcus neoformans and C. gattii are important tools to understand epidemiology and pathogenesis of these pathogens. In this study, a multiplex polymerase chain reaction (PCR) approach was applied to sero-mating typing of C. gattii strains. Four pairs of primers were designed to target 4 allele-specific genes located in the mating-type locus. Twenty-three C. gattii strains, presenting different mating types and serotypes, were tested to validate the method. The method was able to identify all sero-mating allelic patterns including hybrid combinations, and therefore, it represents a simple one-step PCR for sero-mating typing of C. gattii strains.
Generation of a Plasma Microrna (Mirna) Signature Predicting Response to Metronomic Chemotherapy (Mc) for Advanced Breast Cancer (Abc)
Authors: U. Emmenegger, B.A. Sousa, V.C. Hoang, A. Chow, M. Clemons, S. Dent, N.S. Wong, R. Kerbel, M.E. Trudeau, J. Slingerland, A. Eisen, J.M. Ebos, K. Chan, S. Gardner, K. Pritchard
Journal: Annals of Oncology (2014)
Late-breaking abstract: Heart rate variability (HRV) in patients with severe obstructive sleep apnea syndrome (OSA) and its response to a 3-month continuous positive airway pressure (CPAP) therapy
Authors: Pawel Nastalek, Wojciech Skucha, Aleksander Kania, Filip Mejza, Ewa Nizankowska-Mogilnicka, Krzysztof Sladek, Grażyna Bochenek
Journal: European Respiratory Journal (2014)

Introduction: OSA is a known cardiovascular risk factor. Decreased HRV proved to be a predictor of cardiovascular mortality. Aims: To evalute HRV and its changes due to CPAP therapy in severe OSA patients. Methods: Severe OSA patients (n=39) (A) treated with CPAP and control non-OSA patients (n=15) (B) were studied. Group A underwent 3 sleep studies: basal, with CPAP titration and after 3-month CPAP therapy. Group B underwent basal sleep study. Basal 24-hour electrocardiograms (ECG) were performed and standard deviations of NN intervals (SDNN) in 24-hour period were analyzed. Sequent 24-hour ECGs were performed and changes of SDNN were evaluated after a 3-month CPAP therapy. Results: In A group mean age was 54.4 (±2.9) yrs vs. 55.2 (±2.7) in B group, mean body mass index (BMI) was 33.92 (±2.41) kg/m² vs. 31.73 (±1.16), mean apnea-hypopnea index (AHI) was 51.31 (±15,23) per hour vs. 2.45 (±1.28), overall desaturation index (ODI) was 49.28 (±18.5) per hour vs. 1.91 (±0,98), respectively. Basal SDNN was 117.03 (±24.33) ms in A group vs. 137.73 (±13.87) in B group, (p<0.05). There was a negative correlation between AHI, ODI and SDNN in A group (Table 1). After a 3-month CPAP therapy SDNN rose to 140.9 (±22.72) ms vs. basal value 117.03 (±24.33), (p<0.01). More intense CPAP usage correlated positively with SDNN improvement (Table 1).

View this table:

Table 1. Correlation of selected parameters and SDNN (group A)





Conclusion: OSA patients are characterized by decreased HRV. CPAP therapy normalizes HRV in severe OSA patients.