tbuckley/cabot-search huggingface dataset:
Matriptase triggers pleiotropic functional responses in normal human lung fibroblasts (NHLF): Potential relevance in pathophysiology
Authors: Olivier Bardou, Charlene Francois, Bruno Crestani, Keren Borensztajn
Journal: European Respiratory Journal (2014)

Matriptase is a recently identified membrane-anchored serine protease. Its involvement in pathophysiological processes, such as development and cancer, is compelling, although the underlying molecular mechanisms are elusive. Matriptase is physiologically expressed in the lung, but its actions on NHLF remain unknown. In this study, we performed unbiased screening of signaling pathways and gene expression triggered by matriptase on NHLF.  8´105 NHLF were serum-starved overnight, then stimulated with matriptase (10 nM), either for 10 min for kinome profiling, or for 24h for gene array studies. Cell lysate was used with P-receptor tyrosine kinase and P-kinase array kits, or for mRNA extraction and amplification with RT2 profiler PCR array.  Among 92 kinases analyzed, matriptase inhibited the phosphorylation of 17 kinases including EGFR, DDR, EPHB, STAT5 and p53, while it activated the phosphorylation of 27 kinases including INSR, EPHA, MAPK and SRC pathways. Gene array analysis revealed that of the 84 genes tested, matriptase downregulated 8 genes including CCR2 and CCL11, mainly involved in immune response. By contrast, matriptase increased the expression of 40 genes including integrins, growth factors and TIMPs. Functional annotations based on Gene ontology revealed that the kinases and the genes modulated by matriptase are involved in biological processes such as cell differentiation, motility, growth, wound-healing, and matrix organization.  We conclude that matriptase triggers pleiotropic responses on NHLF, which may generate novel insights into an intimate understanding of matriptase pathophysiological functions in the lung.
Src is constitutively activated in non-small cell lung cancer cells with mutant epidermal growth factor receptor and contributes to cell survival
Authors: Jie Zhang, Shailaja Kalyankrishna, Faye M. Johnson, Jonathan M. Kurie
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

171 

Non-small cell lung cancer (NSCLC) cells with activating mutations in the kinase domain of epidermal growth factor receptor (EGFR) require EGFR activity for survival. EGFR activates a variety of intra-cellular signaling pathways; which pathways are required for cell survival has not been defined. Here we examined the role of Src, a protein tyrosine kinase that is activated by EGFR. We found that Src was activated in NSCLC cells with EGFR genetic mutations but not in cell lines with wide-type EGFR. Treatment with PP1, a specific Src inhibitor, induced apoptosis of NSCLC cells with EGFR mutations but not those with wild-type EGFR. PP1 treatment decreased EGFR phosphorylation at the known Src phosphorylation site (Tyr845) as well as one of the major EGFR auto-phosphorylation sites (Tyr1068). Combined treatment with an inhibitor of EGFR and PP1 enhanced apoptosis relative to the effect of either drug alone. Cooperation between these drugs was also observed at the biochemical level (markers of apoptosis and EGFR- and Src-dependent signaling). Thus, Src activation may be a pro-survival signal in NSCLC cells with EGFR mutations, and strategies to inhibit both EGFR and Src may have enhanced efficacy in patients with EGFR-mutant NSCLC.
Drug points: Increased female sexual response after oxytocin
Authors: M Anderson-Hunt, L Dennerstein
Journal: BMJ (1994)

A 26 year old woman pre- sented 17 months after the birth of her second child for some temporary help with the breast feeding of her nephew.The breast feeding of her child had been intermittent after 6-8 months and ceased at 15 months.Lactogenesis had continued with minimal milk expressed.A 28-32 day menstrual cycle had returned by 12 months post partum.A progestogen only pill (levonorgestrel 30 ,ug) had been used since 15 months.A synthetic oxytocin spray (Synto- cinon; Sandoz) was used on day 17 of
Unique Antiplatelet Effects of a Novel S-Nitrosoderivative of a Recombinant Fragment of von Willebrand Factor, AR545C: In Vitro and Ex Vivo Inhibition of Platelet Function
Authors: Aida Inbal, Osnat Gurevitz, Ilia Tamarin, Regina Eskaraev, Angela Chetrit, Ilia Novicov, Monica Feldman, David Varon, Michael Eldar, Joseph Loscalzo
Journal: Blood (1999)
The influence of continuous positive airway pressure treatment on echocardiographic parameters of systolic and diastolic function of the left ventricle
Authors: Milan Sova, Eliska Sovova, Milada Hobzova, Jana Zapletalova, Sona Panakova, Monika Zurkova, Eva Koukalova, Vitezslav Kolek
Journal: European Respiratory Journal (2013)

Aim: The aim of this study was to compare echocardiographic parameters of systolic and diastolic function of the left ventricle in patients with obstructive sleep apnea (OSA) before and after one year of continuous positive airway pressure (CPAP) treatment. As a control group we used patients who were not treated.

Methods: 78 patients (68 men, average age 52.74 years) with OSA indicated to CPAP treatment were evaluated by echocardiography at the baseline and after one year of CPAP treatment. The control group was comprised of 42 patients (35 men, average age 54.38 years) with OSA not indicated for CPAP treatment. We assessed parameters of OSA severity, chosen parameters of heart function (left ventricle TEI, isovolumic contraction time (ICT), parameters of diastolic function- dopplerometric assessment of mitral valve flow and tissue doppler imaging examination of left ventricle).

Results: In patients treated with CPAP we observed statistically significant changes of Epworth sleepiness scale (p<0.0001), apnea-hypopnea index (p<0.0001), average night oxygen saturation (p<0.0001), oxygen desaturation index (p<0.0001), % of sleep time in oxygen saturation < 90% (p<0.0001), left ventricle ICT (p=0.046). The following parameters had not in the comparison with control group changed significantly: left ventricle TEI (p=0.79) and parameters of diastolic function of left ventricle (p=0.406)

Conclusion: CPAP treatment does not improve left ventricle TEI or parameters of diastolic function of the left ventricle.
Zealous self-help groups as adjuncts to psychiatric treatment: a study of Recovery, Inc
Authors: M Galanter
Journal: American Journal of Psychiatry (1988)

In a controlled study of Recovery, Inc., a self-help program for people with psychiatric problems, the author found a decline in both symptoms and concomitant psychiatric treatment after subjects had joined the group. Scores for neurotic distress reported after joining were considerably lower than those reported for the period before joining. Scores for psychological well-being of longstanding Recovery members were no different from those of community control subjects, and fewer long-term members than recent members were being treated with psychotropic medication and psychotherapy. The author concludes that peer-led self-help groups have value as an adjunct to psychiatric treatment.
Wnt-5a signaling restores tamoxifen sensitivity in estrogen receptor negative breast cancer cells.
Authors: Ford Caroline, Elin Ekstrom, Tommy Andersson
Journal: Clinical Cancer Research (2008)

A17   One third of all breast cancers are estrogen receptor alpha (ERα) negative, have a poor overall prognosis and do not respond well to currently available endocrine therapies. New treatment strategies are therefore required. Loss of Wnt-5a has been correlated with loss of ERα expression in clinical breast cancer samples. Therefore, we sought to further investigate the association between ERα and Wnt-5a in breast cancer.  Three breast cancer cell lines (MDA-MB-231, MDA-MB-468 and 4T1) lacking endogenous expression of ERα and Wnt-5a, and one breast cancer cell line (MCF7) expressing both proteins were utilized in this study. Wnt-5a signaling was generated in these cells via stimulation with either recombinant Wnt-5a protein (rW5a) or a Wnt-5a derived hexapeptide (Foxy-5) possessing properties of Wnt-5a signaling. ERα expression was restored at both mRNA and protein levels following treatment with rW5a or Foxy-5. Upregulated ERα was also active, as measured by Ser118 phosphorylation and capable of downstream transcription of progesterone receptor. Most significantly, breast cancer cells re-expressing ERα responded to treatment with the selective estrogen receptor modulator Tamoxifen, as measured by induction of apoptosis.  This represents the first evidence that Wnt-5a signaling acts to re-establish ERα expression in ER-negative breast cancer cells. Our data suggests that combinatorial therapy with Foxy-5 and Tamoxifen should be considered as a future treatment possibility for ER-negative breast cancer patients.
Cytarabine and CNS toxicity.
Authors: W G Peters, R Willemze
Journal: Journal of Clinical Oncology (1992)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1992.10.1.169 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1727919 Cytarabine and CNS toxicity. W G PetersxW G PetersSearch for articles by this author , R WillemzexR WillemzeSearch for articles by this author https://doi.org/10.1200/JCO.1992.10.1.169 PDF "Cytarabine and CNS toxicity.." Journal of Clinical Oncology, 10(1), p. 169© 1992 by American Society of Clinical Oncology
Abstract 2084: Measurement of Health Outcomes After Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Graft (CABG): Better Physical Features with PCI vs. Quality of Life with CABG
Authors: Satomi Seki, Noboru Motomura, Koichiro Kinugawa, Minoru Ono, Atsushi Yao, Naoko Kato, Naomi Ito, Keiko kazuma
Journal: Circulation (2008)

Objectives: There remains a controversy as to which is a better treatment for multi-vessel coronary artery disease (CAD): percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). Although the mortality and morbidities in those patients have been frequently evaluated, only a few studies reported on their health outcomes. The purpose of this study is to measure and compare the health outcomes in these patients in the Japanese population by using a disease-specific scale. Methods: A total of 354 patients were recruited from a university hospital in Tokyo. A cross-sectional postal survey was conducted by mailing self-administered questionnaires that measured health outcomes, and 331 patients (93.5%) responded. The selected disease-specific scale was the Japanese version of the Seattle Angina Questionnaire (SAQ-J). The score of each domain in the SAQ-J was set between 0 and 100. The higher the score, the better the outcome. Analysis of variance was used to analyze the data. Results: Non-PCI and non-CABG responders and those with incomplete responses were eliminated from the study, and data from 131 patients (PCI = 55, CABG = 76) were analyzed. The mean ages for PCI and CABG were 67.9 ± 9.5 and 69.6 ± 9.7 (mean ± SD), and the number of males was 46 (83.6%) and 68 (89.5%), respectively. The average interval between the procedure and the survey was 6.5 ± 8.0 and 7.6 ± 7.4 years, respectively. The number of 3-vessel CAD patients in PCI and CABG groups were 20 (36.4%) and 58 (76.3%)(P &lt; 0.001). In terms of health outcomes after PCI and CABG, the PCI group had a significantly better score than the CABG group under the physical limitation domain of the SAQ-J (79.2 ± 19.7 vs. 71.5 ± 22.0; P = 0.005). On the other hand, the CABG group had a significantly better score in the quality of life (QOL) domain (70.9 ± 23.0 vs. 79.4 ± 18.1; P = 0.025). There was no significant difference between PCI and CABG in terms of anginal stability, anginal frequency, and treatment satisfaction. Conclusions: This is the first study to compare the health outcomes with PCI and CABG by using a disease specific scale in Japanese patients. The patients with CABG had a better QOL outcome than those with PCI. On the other hand, they were more likely to have physical limitations than the PCI group.
Bergapten drives autophagy through the up-regulation of PTEN expression in breast cancer cells
Authors: Francesca De Amicis, Saveria Aquila, Catia Morelli, Carmela Guido, Marta Santoro, Ida Perrotta, Loredana Mauro, Francesca Giordano, Alessandra Nigro, Sebastiano Andò, Maria L Panno
Journal: Molecular Cancer (2015)

Bergapten (5-methoxypsoralen), a natural psoralen derivative present in many fruits and vegetables, has shown antitumoral effects in a variety of cell types. In this study, it has been addressed how Bergapten in breast cancer cells induces autophagic process.In MCF7 and ZR-75 breast cancer cells Bergapten exhibited anti-survival response by inducing the autophagic process increasing Beclin1, PI3KIII, UVRAG, AMBRA expression and conversion of LC3-I to LC3-II. LC3-GFP, Acridine orange assay and transmission electron microscopy even confirmed the increased autophagosome formations in treated cells. Bergapten-induced autophagy is dependent by PTEN up-regulation, since silencing this gene, the induction of Beclin1 and the p-AKT/p-mTOR signal down-regulation were reversed. PTEN is transcriptionally regulated by Bergapten through the involvement of p38MAPK/NF-Y, as evidenced by the use of p38MAPK inhibitor SB203580, site-direct mutagenesis of NF-Y element and NF-Y siRNA. Furthermore NF-Y knockdown prevented Bergapten-induced acid vesicular organelle accumulations (AVOs), strengthening the role of this element in mediating autophagy.Our data indicate PTEN as a key target of Bergapten action in breast cancer cells for the induction of autophagy. These findings add further details on the mechanism of action of Bergapten, therefore suggesting that phytochemical compounds may be implemented in the novel strategies for breast cancer treatment.
Black–White Blood Pressure Disparities: Depressive Symptoms and Differential Vulnerability to Blood Lead
Authors: Margaret T. Hicken, Gilbert C. Gee, Cathleen Connell, Rachel C. Snow, Jeffrey Morenoff, Howard Hu
Journal: Environmental Health Perspectives (2012)

Blacks have higher hypertension rates than whites, but the reasons for these disparities are unknown. Differential vulnerability, through which stress alters vulnerability to the effects of environmental hazards, is an emergent notion in environmental health that may contribute to these disparities.We examined whether blacks and whites exhibit different associations between blood lead (BPb) and blood pressure (BP) and whether depressive symptoms may play a role.Using the National Health and Nutrition Examination Survey 2005-2008, we regressed BP on the three-way interaction among race/ethnicity, BPb, and depressive symptoms in blacks and whites ≥ 20 years of age.Blacks but not whites showed a positive association between BPb and systolic blood pressure (SBP). The disparity in this association between blacks and whites appeared to be specific to the high depressive symptoms group. In the low depressive symptoms group, there was no significant black-white disparity (βinteraction = 0.9 mmHg; 95% CI: -0.9, 2.7). However, of those with high depressive symptoms, blacks and whites had 5.6 mmHg (95% CI: 2.0, 9.2) and 1.2 mmHg (95% CI: -0.5, 2.9) increases in SBP, respectively, in association with each doubling of BPb (βinteraction = 4.4 mmHg; 95% CI: 0.5, 8.3). The pattern of results was similar for diastolic blood pressure.Our results suggest that depressive symptoms may contribute to the black-white disparity in the association between BPb and BP. Depressive symptoms may result, in part, from psychosocial stress. Our results support the notion that stress increases vulnerability to the health effects of environmental hazards and suggest that stress-related vulnerability may be an important determinant of racial/ethnic health disparities.
Invasive mechanical ventilation in community acquired pneumonia
Authors: Catia Cilloniz, Miquel Ferrer, Eva Polverino, Albert Gabarrus, Rosanel Amaro, Jorge Puig de la Bellacasa, Adamantia Liapikou, Jose Mensa, Antoni Torres
Journal: European Respiratory Journal (2014)

Background : Invasive mechanical ventilation (IMV) is frequently used in patients with community-acquired pneumonia (CAP) and severe respiratory failure. However, there is little information on these patients.   Methods : We prospectively enrolled consecutive patients hospitalized with CAP for 12 yrs. We assessed the characteristics and outcomes of patients on IMV, those who needed non-invasive ventilation (NIV) and no ventilatory support, and determined predictors for the need of ventilation and mortality.   Results : Among 3,719 patients included, 154 (4%) required IMV, 136 (4%) NIV, and 3,429 (92%) were not ventilated.  Streptococcus pneumoniae  was the main pathogen. Current alcohol consumption, higher levels of C-reactive protein, worse baseline oxygenation, higher Pneumonia Severity Index, and bacteremia at admission independently predicted the need for IMV, while former tobacco consumption and fever at admission were independently associated with no need for IMV. Likewise, higher levels of C-reactive protein and worse baseline oxygenation independently predicted the need for NIV, while fever at admission was independently associated with no need for NIV. The 30-day mortality was highest in the IMV group, followed by the NIV and non-ventilation groups (51, 33%  vs . 22, 16% and 192, 6%, respectively, pl0.001). Both the need for NIV and IMV independently predicted 30-day mortality in the multivariate analysis.   Conclusion:  Even alter adjustment for higher baseline severity, the need for NIV and IMV independently predicted mortality. Identification of these predictors may help in the initial management and hospital allocation of patients.   Supported : CibeRes (CB06/06/0028)-ISCiii, 2009 SGR 911, and IDIBAPS.
Frequent detection of rhinovirus in bronchoalveolar lavage samples from children with cystic fibrosis
Authors: Elisabeth Kieninger, Caroline Tapparel, M.-N. Kronig, F. Singer, P. Latzin, Hui-Leng Tan, Cara Bossley, C. Casaulta, Andrew Bush, Jane C. Davies, Laurent Kaiser, Nicolas Regamey
Journal: European Respiratory Journal (2011)

Background:  Rhinovirus (RV)-induced chest exacerbations are common in cystic fibrosis (CF) and have been associated with impaired virus clearance by the CF airway epithelium.   Hypothesis:  As a consequence RV can be frequently detected in lower airways of CF children.   Patients and methods:  Bronchoalveolar lavage (BAL) samples were collected from children with CF (n=93), non-CF bronchiectasis (n=26), asthma (n=19) and control children without lower respiratory tract disease (n=21) at a median (IQR) age of 6.7 (2.5-10.8) years. RV load was assessed by RT-PCR. Prevalence of RV infection and RV load were compared between groups and related to demographic and clinical parameters.   Results:  RV was detected in 58 samples (36% of total) and more often in younger children  3 ) compared to asthmatic (2.3 [2.1-4.8] ×10 3 ) (p=0.02), non-CF bronchiectasis (11 [3.5-193] ×10 3 ) (p=0.03) and healthy children (0.8 [0.4-6.5] ×10 3 ) (p=0.001). RV prevalence was similar in CF patients in whom BAL was performed during chest exacerbation (n=20) and phases of clinical stability (n=17). However, RV load was higher during exacerbation (859 [20-3380] ×10 3  vs. 25 [5.8-277] ×10 3 ), p=0.01) and inversely related to FEV1 (%predicted) (r=-0.52, p=0.004).   Conclusions:  RV is frequently detected in the lower airways of CF children. High RV loads during chest exacerbations and in children with advanced lung disease suggest a possible role for RV in CF lung disease progression.
Androgen Suppression Plus Radiation for Prostate Cancer
Authors: Jeremy Millar
Journal: JAMA (2004)

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IL-17 enhances IL-8 production by attenuating both the ARE-mediated and the microRNA-mediated degradation of IL-8 mRNA
Authors: Saheli Chowdhury, Annemiek Dijkhuis, Rene Lutter
Journal: European Respiratory Journal (2011)

Background:  Interleukin (IL)-17 is a cytokine implicated in chronic inflammation. Enhanced amounts of IL-17 have been found in the airways of patients with asthma and COPD. Previously we have reported that IL-17 potentiates TNF-α or IL-1β-induced IL-8 and IL-6 production in human lung epithelial cells, predominantly by stabilizing IL-6 and IL-8 mRNA.   Aim:  IL-6 and IL-8 mRNA contain AU-rich elements (ARE) in the 39UTR, targeting these mRNAs for facilitated degradation. This decay pathway may be mediated by AU-binding proteins (AU-bps) and possibly microRNAs (miRs). We have assessed whether AUBps (TTP, KHSRP, AUF1) and/or miRs are involved in IL-8 mRNA degradation. And, if so, whether IL-17 modulates these pathways.   Results:  Inhibition of miR16, or knock-down of TTP or KHSRP resulted in a marked increase of TNF-α-induced IL-8 production, which was paralleled by stabilizing IL-8 mRNA. Conversely, knock-down of AUF-1 reduced IL-8 production and promoted degradation of IL-8 mRNA. IL-17 halts IL-8 mRNA degradation by enhancing the role of AUF1 which protects IL-8 mRNA from degradation. Furthermore, IL-17 reverses the TNF-α-induced production of miR16.   Discussion:  These findings strongly indicate that IL-17 enhances IL-8 production by attenuating two pathways that degrade IL-8 mRNA. We have obtained similar data for several other inflammatory mediators. Since airway epithelial cells from patients with asthma display enhanced IL-8 production we are assessing whether there is an intrinsic disturbance in these mRNA decay pathways.  This work is supported by the Netherlands Asthma Foundation (3.2.06.031)
Evaluation of a ‘DIY’ Test for the Detection of Colorectal Cancer
Authors: J J T Tate, J Northway, G T Royle, I Taylor
Journal: Journal of the Royal Society of Medicine (1989)

A new type of faecal occult blood test, EZ-Detect™, has been evaluated in 404 patients presenting with symptoms suggestive of colorectal disease. The test avoids handling of stools and gives a result which patients can read themselves - factors which may increase patient compliance. In comparison with the Haemoccult™ test, EZ-Detect has the same sensiti-vity for blood in laboratory conditions. In clinical use 98% of patients expressed a preference for EZ-Detect but it detected significantly fewer patients with cancer than did Haemoccult (P = &lt; 0.05). In its present form, this type of test would be unsuitable for population screening for colorectal cancer even if improved compliance is achieved.