tbuckley/cabot-search huggingface dataset:
Exogenous Surfactant Kinetics in Infant Respiratory Distress Syndrome: A Novel Method with Stable Isotopes
Authors: MIRKA TORRESIN, LUC J. I. ZIMMERMANN, PAOLA E. COGO, PAOLA CAVICCHIOLI, TAMARA BADON, GIUSEPPE GIORDANO, FRANCO ZACCHELLO, PIETER J. J. SAUER, VIRGILIO P. CARNIELLI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Little is known about surfactant metabolism in newborn infants, since radioactive isotopes cannot be used in humans. We describe here a new method for studying exogenous surfactant pharmacokinetics in vivo. We measured surfactant half-life, pool size, and turnover time in eight preterm infants (gestational age: 30 +/- 2 wk; birth weight: 1,416 +/- 202 g) who were mechanically ventilated because of infant respiratory distress syndrome. We administered two doses of 100 mg/kg each of a natural porcine surfactant with (13)C-labeled dipalmitoylphosphatidylcholine as a tracer. The (13)C enrichment of surfactant disaturated phosphatidylcholine (DSPC) was measured in serial tracheal aspirates by gas chromatography-mass spectrometry. The DSPC half-life was 34.2 +/- 9.4 h (mean +/- SD; range: 21.8 to 45.9 h). The apparent DSPC pool sizes were 5.8 +/- 6.1 mg/kg (range: 0.1 to 17.0 mg/kg) and 17.3 +/- 13.6 mg/kg (range: 3.3 to 41.0 mg/kg) at the time of the first and second surfactant doses, respectively. We present a novel and safe method that allows the tracing of exogenous surfactant phosphatidylcholine, the major lipid component of pulmonary surfactant, in infants who receive exogenous surfactant. This method could be a valuable tool for studying: (1) therapies that enhance lung/surfactant maturation; (2) the dosing and timing of surfactant therapy in different lung diseases; and (3) the comparison of different surfactant preparations.
<i>HER2</i> Amplification: A Potential Mechanism of Acquired Resistance to EGFR Inhibition in <i>EGFR</i>-Mutant Lung Cancers That Lack the Second-Site <i>EGFR</i>T790M Mutation
Authors: Ken Takezawa, Valentina Pirazzoli, Maria E. Arcila, Caroline A. Nebhan, Xiaoling Song, Elisa de Stanchina, Kadoaki Ohashi, Yelena Y. Janjigian, Paula J. Spitzler, Mary Ann Melnick, Greg J. Riely, Mark G. Kris, Vincent A. Miller, Marc Ladanyi, Katerina Politi, William Pao
Journal: Cancer Discovery (2012)

Abstract EGF receptor (EGFR)–mutant lung cancers eventually become resistant to treatment with EGFR tyrosine kinase inhibitors (TKI). The combination of EGFR-TKI afatinib and anti-EGFR antibody cetuximab can overcome acquired resistance in mouse models and human patients. Because afatinib is also a potent HER2 inhibitor, we investigated the role of HER2 in EGFR-mutant tumor cells. We show in vitro and in vivo that afatinib plus cetuximab significantly inhibits HER2 phosphorylation. HER2 overexpression or knockdown confers resistance or sensitivity, respectively, in all studied cell line models. FISH analysis revealed that HER2 was amplified in 12% of tumors with acquired resistance versus only 1% of untreated lung adenocarcinomas. Notably, HER2 amplification and EGFRT790M were mutually exclusive. Collectively, these results reveal a previously unrecognized mechanism of resistance to EGFR-TKIs and provide a rationale to assess the status and possibly target HER2 in EGFR-mutant tumors with acquired resistance to EGFR-TKIs. Significance: Because all EGFR-mutant lung adenocarcinomas eventually develop resistance to TKI therapy, understanding mechanisms of acquired resistance may improve clinical outcomes. These results implicate HER2 as a novel protein involved in the sensitivity or resistance of EGFR-mutant lung cancer and provide a rationale to assess the status of and possibly target HER2 in such tumors. Cancer Discov; 2(10); 922–33. ©2012 AACR. Read the Commentary on this article by Blakely and Bivona, p. 872. This article is highlighted in the In This Issue feature, p. 857.
Polymorphic Competence Peptides Do Not Restrict Recombination in Streptococcus pneumoniae
Authors: O. E. Cornejo, L. McGee, D. E. Rozen
Journal: Molecular Biology and Evolution (2009)

Understanding the factors that limit recombination in bacteria is critical in order to better understand and assess its effects on genetic variation and bacterial population genetic structure. Transformation in the naturally competent bacterium, Streptococcus pneumoniae, is regulated by a polymorphic competence (com) apparatus. It has been suggested that polymorphic types, called pherotypes, generate and maintain subpopulation genetic structure within this species. We test predictions stemming from this hypothesis using a cosmopolitan sample of clinical pneumococcal isolates. We sequenced the locus encoding the peptide that induces competence (comC) to assign clones to each known pherotype class and then used multilocus sequence typing to determine whether there is significant genetic differentiation between pherotypes subgroups. We find two dominant pherotypes within our sample, and both are maintained at high frequencies (CSP1 74%, CSP2 26%). Our analyses fail to detect significant genetic differentiation between pherotype groups and find strong evidence, from a coalescent analysis, for interpherotype recombination. In addition, our analyses indicate that positive selection may account for the maintenance of the fixed polymorphism in this locus (comC). Altogether, these results fail to support the prediction that the polymorphism in the competence system acts to limit recombination within S. pneumoniae populations. We discuss why this result is expected given the mechanism underlying transformation and outline a scenario to explain the evolution of polymorphism in the competence system.
Psychological status of COPD patients on long term oxygen therapy
Authors: J Borak, P Sliwinski, Z Piasecki, J Zielinski
Journal: European Respiratory Journal (1991)

We evaluated the psychological status of chronic obstructive pulmonary disease patients with chronic respiratory failure, who were qualified for or on long-term oxygen therapy. Forty eight patients were examined. The patients' psychological status was assessed by means of the following methods: detailed clinical interview, the Taylor Manifest Anxiety Scale (MAS), Beck's Depression Inventory, and Tylka's Psychological Evaluation of Rehabilitation Efficiency Scale (SOPER). The study demonstrated that the great majority of patients presented a high degree of anxiety, depression and psychological tension, had low self-esteem and did not believe in the efficiency of therapy.
Got Calcium? Welcome to the Calcium-Alkali Syndrome
Authors: Ami M. Patel, Stanley Goldfarb
Journal: Journal of the American Society of Nephrology (2010)

We recommend changing the name of the milk-alkali syndrome to the calcium-alkali syndrome, because the new terminology better reflects the shifting epidemiology and understanding of this disorder. The calcium-alkali syndrome is now the third most common cause of hospital admission for hypercalcemia, and those at greatest risk are postmenopausal or pregnant women. The incidence of the calcium-alkali syndrome is growing in large part as a result of the widespread use of over-the-counter calcium and vitamin D supplements. Advertising for treatment or prevention of osteoporosis has long encouraged this use. Intricate mechanisms mediating the calcium-alkali syndrome depend on interplay among intestine, kidney, and bone. New insights regarding its pathogenesis focus on the key role of calcium-sensing receptors and TRPV5 channels in the modulation of renal calcium excretion. Restoring extracellular blood volume, increasing GFR and calcium excretion, and discontinuing calcium supplementation provide best treatment.
Loss of the Endothelial Glycocalyx Links Albuminuria and Vascular Dysfunction
Authors: Andrew H.J. Salmon, Joanne K. Ferguson, James L. Burford, Haykanush Gevorgyan, Daisuke Nakano, Steven J. Harper, David O. Bates, Janos Peti-Peterdi
Journal: Journal of the American Society of Nephrology (2012)

Patients with albuminuria and CKD frequently have vascular dysfunction but the underlying mechanisms remain unclear. Because the endothelial surface layer, a meshwork of surface-bound and loosely adherent glycosaminoglycans and proteoglycans, modulates vascular function, its loss could contribute to both renal and systemic vascular dysfunction in proteinuric CKD. Using Munich-Wistar-Fromter (MWF) rats as a model of spontaneous albuminuric CKD, multiphoton fluorescence imaging and single-vessel physiology measurements revealed that old MWF rats exhibited widespread loss of the endothelial surface layer in parallel with defects in microvascular permeability to both water and albumin, in both continuous mesenteric microvessels and fenestrated glomerular microvessels. In contrast to young MWF rats, enzymatic disruption of the endothelial surface layer in old MWF rats resulted in neither additional loss of the layer nor additional changes in permeability. Intravenous injection of wheat germ agglutinin lectin and its adsorption onto the endothelial surface layer significantly improved glomerular albumin permeability. Taken together, these results suggest that widespread loss of the endothelial surface layer links albuminuric kidney disease with systemic vascular dysfunction, providing a potential therapeutic target for proteinuric kidney disease.
Nanomolar concentration of NSC606985, a camptothecin analog, induces leukemic-cell apoptosis through protein kinase Cδ–dependent mechanisms
Authors: Man-Gen Song, Shen-Meng Gao, Ke-Ming Du, Min Xu, Yun Yu, Yu-Hong Zhou, Qiong Wang, Zhu Chen, Yuan-Shan Zhu, Guo-Qiang Chen
Journal: Blood (2005)
Induction of Human Arylamine <i>N</i>-Acetyltransferase Type I by Androgens in Human Prostate Cancer Cells
Authors: Neville J. Butcher, Natasha L. Tetlow, Catherine Cheung, Gysell M. Broadhurst, Rodney F. Minchin
Journal: Cancer Research (2007)

Human arylamine N-acetyltransferases (NAT) bioactivate arylamine and heterocyclic amine carcinogens present in red meat and tobacco products. As a result, factors that regulate expression of NATs have the potential to modulate cancer risk in individuals exposed to these classes of carcinogens. Because epidemiologic studies have implicated well-done meat consumption as a risk factor for prostate cancer, we have investigated the effects of androgens on the expression of arylamine N-acetyltransferase type I (NAT1). We show that NAT1 activity is induced by R1881 in androgen receptor (AR)-positive prostate lines 22Rv1 and LNCaP, but not in the AR-negative PC-3, HK-293, or HeLa cells. The effect of R1881 was dose dependent, with an EC(50) for R1881 of 1.6 nmol/L. Androgen up-regulation of NAT1 was prevented by the AR antagonist flutamide. Real-time PCR showed a significant increase in NAT1 mRNA levels for R1881-treated cells (6.60 +/- 0.80) compared with vehicle-treated controls (1.53 +/- 0.17), which was not due to a change in mRNA stability. The increase in NAT1 mRNA was attenuated by concurrent cycloheximide treatment, suggesting that the effect of R1881 may not be by direct transcriptional activation of NAT1. The dominant NAT1 transcript present following androgen treatment was type IIA, indicating transcriptional activation from the major NAT1 promoter P1. A series of luciferase reporter deletions mapped the androgen responsive motifs to a 157-bp region of P1 located 745 bases upstream of the first exon. These results show that human NAT1 is induced by androgens, which may have implications for cancer risk in individuals.
Role of Interleukin 16 in Multiple Myeloma
Authors: D. Atanackovic, Y. Hildebrandt, J. Templin, Y. Cao, C. Keller, J. Panse, S. Meyer, H. Reinhard, K. Bartels, N. Lajmi, O. Sezer, A. R. Zander, A. H. Marx, R. Uhlig, J. Zustin, C. Bokemeyer, N. Kroger
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundMultiple myeloma is a malignancy characterized by the expansion of a plasma cell clone that localizes to the human bone marrow. Myeloma cells and bone marrow stromal cells produce soluble factors that promote the survival and progression of multiple myeloma. Interleukin 16 (IL-16) is involved in regulating the migration and proliferation of normal leukocytes. However, the role of IL-16 in human cancers, including multiple myeloma, is unclear.
HLA AW19, B12 in immunoproliferative small intestinal disease.
Authors: B Nikbin, M Banisadre, F Ala, A Mojtabai
Journal: Gut (1979)

A group of 21 patients with immunoproliferative small intestinal disease (IPSID), 10 with alpha heavy chain paraproteinaemia and 11 without it, were HLA typed. The results were compared with 35 disease controls and 120 normal controls. A significant increase of Aw19 and B12 antigens was noted among the patients compared with the control subjects. The high rate of association of both AW19 and B12 antigens in patients as compared with controls suggests a possible haplotype (Aw19, B12) association with IPSID.
Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery
Authors: H. Takahashi, S. Soma, M. Muramatsu, M. Oka, H. Ienaga, Y. Fukuchi
Journal: European Respiratory Journal (2001)

Since pulmonary vasculature is complex in terms of regional difference in structure and function, it is important to understand the site of endothelin (ET) synthesis and the distribution of the ET system along the axial pathways of pulmonary artery. The expression of big ET-1, ET converting enzyme (ECE) and ET(A) receptors were examined in rat pulmonary arteries under normal and hypoxic conditions using an immunohistochemical method and Northern blot analysis. In normal conditions, big ET-1 was expressed in the intima and media of pulmonary arteries with a predominant distribution in the distal segments and a preferential localization in the media, while ETA receptors were dominantly expressed in the proximal segments. ECE was constitutively expressed in the intima and media. Following exposure to hypoxia, messenger ribonucleic acid (mRNA) expression of ET-1 and ET(A) receptors were up-regulated by two-fold and immunoreactivities for big ET-1, ECE, and ET(A) receptors significantly increased by two to five-fold in the distal segments. Smooth muscle cells are an important source of endothelin-1 in the pulmonary artery. The distribution of big endothelin-1 and endothelin A receptors in pulmonary arteries was discrepant in normal conditions while their expression concomitantly increased in the distal segments in hypoxic conditions. This heterogeneity may play an important role in the regulation of pulmonary vascular tone.
The relation between paracetamol use and asthma: a GA2LEN European case-control study
Authors: S. Shaheen, J. Potts, L. Gnatiuc, J. Makowska, M. L. Kowalski, G. Joos, T. van Zele, Y. van Durme, I. De Rudder, S. Wöhrl, J. Godnic-Cvar, L. Skadhauge, G. Thomsen, T. Zuberbier, K. C. Bergmann, L. Heinzerling, M. Gjomarkaj, A. Bruno, E. Pace, S. Bonini, W. Fokkens, E. J. M. Weersink, C. Loureiro, A. Todo-Bom, C. M. Villanueva, C. Sanjuas, J-P. Zock, C. Janson, P. Burney
Journal: European Respiratory Journal (2008)

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case–control study organised by the Global Allergy and Asthma European Network (GA 2 LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (20–45 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations.
Cost effectiveness of treatment for gastro-oesophageal reflux disease in clinical practice: a clinical database analysis
Authors: A Eggleston, A Wigerinck, S Huijghebaert, D Dubois, A Haycox
Journal: Gut (1998)

Background —Previous evaluations of the cost effectiveness of antireflux medication used in gastro-oesophageal reflux disease (GORD) have been based on results obtained in controlled clinical trials. Unfortunately such an approach does not necessarily identify the therapeutic option which provides the greatest benefit from available resources in real life situations. To make an informed choice requires a recognition that the costs and benefits of therapy in practice may differ from those identified in trials. Aims —To evaluate, based on a retrospective prescription database analysis, the cost effectiveness of alternative treatment options for patients with uncomplicated GORD. The analysis assesses health service resource use during the first six months of treatment in three groups of patients initially prescribed cisapride (CIS), ranitidine (RAN), or omeprazole (OME). Methods —The MediPlus™ UK database was used to identify all health care resources consumed by patients in the three treatment groups during their first six months of treatment. Patients with more complicated GORD, as indicated by initial referral to a specialist or outpatient hospital visit (&lt;13%), were excluded from the analysis. Results —The average cost per patient for the initial six months of treatment for CIS, RAN, and OME based therapies was £136, £177, and £189 per patient, respectively. A major element underlying this cost variation was the acquisition cost and quantity of antireflux medication required by patients. The average number of one month equivalent prescriptions consumed during this six month period was 1.85 (CIS), 2.57 (RAN), and 2.96 (OME) with associated costs of £49 (CIS), £67 (RAN), and £105 (OME). Antacid and alginate/antacid use was higher in the CIS and RAN groups (about 1.0 antacid prescription per patient versus 0.4 for OME), but their contribution to the total cost per patient was less than 2%. The number of general practitioner consultations over the six month period for each treatment group was 2.4 (CIS), 2.9 (RAN), and 2.6 (OME) with associated costs of £60.31 (CIS), £73.06 (RAN), and £65.52 (OME). The average number of non-drug interventions (referrals, outpatient visits, endoscopies, barium meals, or x rays) was 0.34 in the RAN group compared with less than 0.2 in the CIS and OME groups. The costs associated with such interventions were £23.80 (RAN), £9.60 (CIS), and £11.10 (OME) per patient. Conclusion —The data indicate that the “step up” approach, starting with a prokinetic or H 2 receptor antagonist, represents the most cost effective initial therapeutic strategy for a primary care physician to adopt when faced with a patient with first diagnosis of uncomplicated GORD.
Abrogation of Passively Transferred Tumor Immunity &lt;italic&gt;In Vivo&lt;/italic&gt; by Antigenically Related Tumor Cells
Authors: Harold T. Wepsic, Irwin D. Bernstein, Berton Zbar, Tibor Borsos, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1971)

Systemic transfer of tumor immunity in syngeneic guinea pigs, accomplished by transfusion of peritoneal exudate cells, was abrogated after the intraperitoneal injection of live or X-irradiated tumor cells antigenically related to the immunity transferred. Passive transfer of immunity was not affected by the intraperitoneal injection of unrelated tumor cells. The relationships of time of inoculation and dose of tumor cells to abrogation of transferred immunity were studied. The transfer of tumor immunity was also abolished when antigenically related tumor cells were mixed with peritoneal exudate cells before inoculation.
Connexin43 silencing in myofibroblasts prevents arrhythmias in myocardial cultures: role of maximal diastolic potential
Authors: Saïd F. Askar, Brian O. Bingen, Jim Swildens, Dirk L. Ypey, Arnoud van der Laarse, Douwe E. Atsma, Katja Zeppenfeld, Martin J. Schalij, Antoine A. de Vries, Daniël A. Pijnappels
Journal: Cardiovascular Research (2011)

AimsArrhythmogenesis in cardiac fibrosis remains incompletely understood. Therefore, this study aims to investigate how heterocellular coupling between cardiomyocytes (CMCs) and myofibroblasts (MFBs) affects arrhythmogeneity of fibrotic myocardial cultures. Potentially, this may lead to the identification of novel anti-arrhythmic strategies.
Clinical and pharmacological phase I study with accelerated titration design of a daily times five schedule of BBR3464, a novel cationic triplatinum complex
Authors: C. Sessa, G. Capri, L. Gianni, F. Peccatori, G. Grasselli, J. Bauer, M. Zucchetti, L. Viganò, A. Gatti, C. Minoia, P. Liati, S. Van den Bosch, A. Bernareggi, G. Camboni, S. Marsoni
Journal: Annals of Oncology (2000)
c-Jun-NH2-kinase-1 Inhibition Leads to Antitumor Activity in Ovarian Cancer
Authors: Pablo Vivas-Mejia, Juliana Maria Benito, Ariel Fernandez, Hee-Dong Han, Lingegowda Mangala, Cristian Rodriguez-Aguayo, Arturo Chavez-Reyes, Yvonne G. Lin, Mark S. Carey, Alpa M. Nick, Rebecca L. Stone, Hye Sun Kim, Francois-Xavier Claret, William Bornmann, Bryan T.J. Hennessy, Angela Sanguino, Zhengong Peng, Anil K. Sood, Gabriel Lopez-Berestein
Journal: Clinical Cancer Research (2009)

To show the functional, clinical, and biological significance of c-Jun-NH(2)-kinase (JNK)-1 in ovarian carcinoma.Analysis of the impact of JNK on 116 epithelial ovarian cancers was conducted. The role of JNK in vitro and in experimental models of ovarian cancer was assessed. We studied the role of N-5-[4-(4-methyl piperazine methyl)-benzoylamido]-2-methylphenyl-4-[3-(4-methyl)-pyridyl]-2-pyrimidine amine (WBZ_4), a novel JNK inhibitor redesigned from imatinib based on targeting wrapping defects, in cell lines and in experimental models of ovarian cancer.We found a significant association of pJNK with progression-free survival in the 116 epithelial ovarian cancers obtained at primary debulking therapy. WBZ_4 led to cell growth inhibition and increased apoptosis in a dose-dependent fashion in four ovarian cancer cell lines. In vivo, whereas imatinib had no effect on tumor growth, WBZ_4 inhibited tumor growth in orthotopic murine models of ovarian cancer. The antitumor effect was further increased in combination with docetaxel. Silencing of JNK-1 with systemically administered siRNA led to significantly reduced tumor weights compared with nonsilencing siRNA controls, indicating that indeed the antitumor effects observed were due to JNK-1 inhibition.These studies identify JNK-1 as an attractive therapeutic target in ovarian carcinoma and that the redesigned WBZ_4 compound should be considered for further clinical development.