tbuckley/cabot-search huggingface dataset:
<i>Pseudomonas aeruginosa</i> in Chronic Obstructive Pulmonary Disease
Authors: Timothy F. Murphy, Aimee L. Brauer, Karen Eschberger, Phyllis Lobbins, Lori Grove, Xueya Cai, Sanjay Sethi
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Pseudomonas aeruginosa is isolated from adults with chronic obstructive pulmonary disease (COPD) in cross-sectional studies. However, patterns of carriage and the role of P. aeruginosa in COPD are unknown.To elucidate carriage patterns, phenotypes of strains, clinical manifestations, and the antibody response to P. aeruginosa in COPD.A prospective study of adults with COPD was conducted. Isolates of P. aeruginosa were subjected to genotypic and phenotypic analysis. Sputum samples were studied for P. aeruginosa DNA, and immune responses were assayed.We analyzed longitudinal clinical data, sputum cultures, pulsed-field gel electrophoresis of bacterial DNA, polymerase chain reaction of sputum, and immunoblot assays of serum. Fifty-seven episodes of acquisition of strains of P. aeruginosa were observed in 39 of 126 patients over 10 years. Acquisition of a new strain was associated with exacerbation. Thirty-one episodes of carriage were followed by clearance of the strain; 16 were of short (<1 mo) duration. Thirteen strains demonstrated persistence, and 13 strains were of indeterminate duration. Six strains were mucoid and were more likely to persist than nonmucoid strains (P = 0.005). Antibody responses developed in 53.8% of persistent carriage and in only 9.7% of short-term carriage episodes (P = 0.003). Antibiotics did not account for clearance.Two distinct patterns of carriage by P. aeruginosa were observed: (1) short-term colonization followed by clearance and (2) long-term persistence. Mucoid strains showed persistence. Acquisition of P. aeruginosa is associated with the occurrence of an exacerbation. Serum antibody responses do not mediate clearance of P. aeruginosa.
The Combined Expression of CXCR7 and its Ligand CXCL12 is a Marker for Unfavorable Prognosis in Gastric Cancer
Authors: H.J. Lee, K.S. Lee, H. Ryu, I.C. Song, S.M. Huang, H.J. Yun, J. Kim, D.Y. Jo, S. Kim, M.K. Mallath, A. Yelsengekar, S.A. Mehta, P.S. Patil, R. Okita, D. Mougiakakos, K. Yasuda, A. Maeda, T. Yukawa, S. Saisho, Y. Hirami, K. Shimizu, M. Nakata, R. Kiessling, N.G. Tsoukalas, I. Kostakis, M. Tolia, A. Tzovaras, C. Giaginis, I. Sfiniadakis, K. Tsolakis, A. Karameris, E. Patsouris, S. Theocharis, M.S. Liew, C. Murone, M. Walkiewicz, P. Mitchell, H. Gan, S. Barnett, P. Russell, G. Wright, A. Scott, T. John, T. Fujii, S. Yamada, N. Okumura, B.C. Fuchs, M. Suenaga, G. Nakayama, H. Sugimoto, S. Takeda, K.K. Tanabe, Y. Kodera, H. Iwasaki, K. Nakano, H. Onishi, M. Katano, A. Amann, M. Zwierzina, M. Bitsche, G. Gamerith, J. Huber, S. Koeck, J. Kelm, W. Hilbe, H. Zwierzina, Y. Ohara, T. Oda, Y. Akashi, R. Miyamoto, K. Yamada, S. Hashimoto, N. Ohkohchi, G. Gerotziafas, M.P. Roman, E. Mdemba, M. Hatmi, J. Fareed, J.F. Bernaudin, I. Elalamy, F. Paksoy Türköz, M. Solak, O. Keskin, Z. Arık, F.S. Sarıcı, H. Petekkaya, T. Babacan, K.M. Altunda, S. Camilleri-Broet, A. Stanczak, A. Brozyna, H. Wisniewska, W. Jozwicki, L. Bodnar, M. Lamparska-Przybysz, M. Wieczorek, M. Nomura, J. Mobley, D. Chen, T. Ohira, N. Gotoh, A.F. Gazdar, N. Ikeda, Z. Tomasevic, D. Kolarevic, Z. Milovanovic, M. Inomata
Journal: Annals of Oncology (2012)
Retained Lens Fragments after Phacoemulsification
Authors: Judy E. Kim, Harry W. Flynn, William E. Smiddy, Timothy G. Murray, Patrick E. Rubsamen, Janet L. Davis, Don H. Nicholson
Journal: Ophthalmology (1994)

The authors present the clinical features of patients with retained lens fragments after phacoemulsification and their outcome after pars plana vitrectomy.The authors performed a retrospective chart review of 62 patients who had surgical management of posteriorly dislocated lens fragments after phacoemulsification during the 3-year period from January 1990 to December 1992.Eight of the 62 patients underwent vitrectomy on the same day as the cataract surgery. Of the remaining 54 patients examined in the outpatient clinic, initial clinical features included marked intraocular inflammation (87%), elevated intraocular pressure of 30 mmHg or higher (46%), and corneal edema (46%). Retinal detachment was present before vitrectomy in one patient and occurred after vitrectomy in two others. Initial visual acuity was 20/200 or worse in 68% of patients. After vitrectomy, final visual acuity was 20/40 or better in 68% of patients. Using the percentage of patients with 20/40 or better final visual acuity, there was no statistically significant difference in surgery performed within 7 days (70%), between 1 and 4 weeks (60%), and after 4 weeks (70%). Twenty (80%) of 25 patients with initial posterior chamber intraocular lenses (PC IOLs) and 16 (62%) of 26 patients with initial anterior chamber IOLs (AC IOLs) achieved 20/40 or better visual acuity. A visual acuity outcome of 20/200 or worse occurred in all three patients with retinal detachment. Six of the eight patients who underwent vitrectomy on the same day as the cataract surgery achieved 20/30 or better visual acuity.The timing of vitrectomy did not influence visual acuity outcomes. Intraocular lenses inserted at the primary operation did not adversely affect the visual outcome. However, vitrectomy on the same day as cataract surgery generally yielded favorable visual acuity outcomes and eliminated the need for a second operation at a later date. In most patients with retained lens fragments, management with vitrectomy allowed good visual acuity outcomes.
Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor Are Associated with Improved Survival in Gefitinib-Treated Chemorefractory Lung Adenocarcinomas
Authors: Miguel Taron, Yukito Ichinose, Rafael Rosell, Tony Mok, Bartomeu Massuti, Lurdes Zamora, Jose Luis Mate, Christian Manegold, Mayumi Ono, Cristina Queralt, Thierry Jahan, Jose Javier Sanchez, Maria Sanchez-Ronco, Victor Hsue, David Jablons, Jose Miguel Sanchez, Teresa Moran
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) confer a strong sensitivity to gefitinib, a selective tyrosine kinase inhibitor of EGFR. Experimental Design: We examined EGFR mutations at exons 18, 19, and 21 in tumor tissue from 68 gefitinib-treated, chemorefractory, advanced non–small cell lung cancer patients from the United States, Europe, and Asia and in a highly gefitinib-sensitive non–small cell lung cancer cell line and correlated their presence with response and survival. In addition, in a subgroup of 28 patients for whom the remaining tumor tissue was available, we examined the relationship among EGFR mutations, CA repeats in intron 1 of EGFR, EGFR and caveolin-1 mRNA levels, and increased EGFR gene copy numbers. Results: Seventeen patients had EGFR mutations, all of which were in lung adenocarcinomas. Radiographic response was observed in 16 of 17 (94.1%) patients harboring EGFR mutations, in contrast with 6 of 51 (12.6%) with wild-type EGFR (P &amp;lt; 0.0001). Probability of response increased significantly in never smokers, patients receiving a greater number of prior chemotherapy regimens, Asians, and younger patients. Median survival was not reached for patients with EGFR mutations and was 9.9 months for those with wild-type EGFR (P = 0.001). EGFR mutations tended to be associated with increased numbers of CA repeats and increased EGFR gene copy numbers but not with EGFR and caveolin-1 mRNA overexpression (P = not significant). Conclusions: The presence of EGFR mutations is a major determinant of gefitinib response, and targeting EGFR should be considered in preference to chemotherapy as first-line treatment in lung adenocarcinomas that have demonstrable EGFR mutations.
No difference in mortality between low and high PEEP
Authors: P Bhatia
Journal: Thorax (2004)

▴ The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med2004;351:327–36 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Positive end expiratory pressure (PEEP) during ventilation improves arterial oxygenation by recruiting alveoli, but it may cause circulatory depression and increase airway pressure and lung volumes resulting in ventilator induced lung injury from overdistension. In acute lung injury and acute respiratory distress syndrome (ARDS), mechanical ventilation is critical for the survival … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DThe%2BNational%2BHeart%252C%2BLung%252C%2Band%2BBlood%2BInstitute%2BARDS%26rft.auinit1%253D%2B%26rft.volume%253D351%26rft.issue%253D4%26rft.spage%253D327%26rft.epage%253D336%26rft.atitle%253DHigher%2Bversus%2BLower%2BPositive%2BEnd-Expiratory%2BPressures%2Bin%2BPatients%2Bwith%2Bthe%2BAcute%2BRespiratory%2BDistress%2BSyndrome%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa032193%26rft_id%253Dinfo%253Apmid%252F15269312%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa032193&link_type=DOI [3]: /lookup/external-ref?access_num=15269312&link_type=MED&atom=%2Fthoraxjnl%2F59%2F10%2F842.atom [4]: /lookup/external-ref?access_num=000222801200006&link_type=ISI
Pharmacogenetic Pathway Analysis for Determination of Sunitinib-Induced Toxicity
Authors: Nielka P. van Erp, Karel Eechoute, Astrid A. van der Veldt, John B. Haanen, An K.L. Reyners, Ron H.J. Mathijssen, Epie Boven, Tahar van der Straaten, Renée F. Baak-Pablo, Judith A.M. Wessels, Henk-Jan Guchelaar, Hans Gelderblom
Journal: Journal of Clinical Oncology (2009)

To identify genetic markers in the pharmacokinetic and pharmacodynamic pathways of sunitinib that predispose for development of toxicities: thrombocytopenia, leukopenia, mucosal inflammation, hand-foot syndrome, and any toxicity according to National Cancer Institute Common Toxicity Criteria higher than grade 2.A multicenter pharmacogenetic association study was performed in 219 patients treated with single-agent sunitinib. A total of 31 single nucleotide polymorphisms in 12 candidate genes, together with several nongenetic variants, were analyzed for a possible association with toxicity. In addition, genetic haplotypes were developed and related to toxicity.The risk for leukopenia was increased when the G allele in CYP1A1 2455A/G (odds ratio [OR], 6.24; P = .029) or the T allele in FLT3 738T/C (OR, 2.8; P = .008) were present or CAG in the NR1I3 (5719C/T, 7738A/C, 7837T/G) haplotype (OR, 1.74; P = .041) was absent. Any toxicity higher than grade 2 prevalence was increased when the T allele of vascular endothelial growth factor receptor 2 1191C/T (OR, 2.39; P = .046) or a copy of TT in the ABCG2 (-15622C/T, 1143C/T) haplotype (OR, 2.63; P = .016) were present. The risk for mucosal inflammation was increased in the presence of the G allele in CYP1A1 2455A/G (OR, 4.03; P = .021) and the prevalence of hand-foot syndrome was increased when a copy of TTT in the ABCB1 (3435C/T, 1236C/T, 2677G/T) haplotype (OR, 2.56; P = .035) was present.This exploratory study suggests that polymorphisms in specific genes encoding for metabolizing enzymes, efflux transporters, and drug targets are associated with sunitinib-related toxicities. A better understanding of genetic and nongenetic determinants of sunitinib toxicity should help to optimize drug treatment in individual patients.
Electrical Remodeling of the Atria Following Loss of Atrioventricular Synchrony
Authors: Paul B. Sparks, Harry G. Mond, Jitendra K. Vohra, Shenthar Jayaprakash, Jonathan M. Kalman
Journal: Circulation (1999)

Background —Evidence suggests that an increased incidence of atrial fibrillation occurs in patients undergoing single-chamber ventricular pacing (VVI) when compared with those undergoing single-chamber atrial pacing (AAI) or those having dual-chamber atrioventricular pacing (DDD). The mechanism for this is unknown. We hypothesized that long-term loss of atrioventricular (AV) synchrony leads to atrial electrical remodeling: a potential explanation for this difference. Methods and Results —The study was a prospective, randomized comparison between 18 patients paced in VVI mode and 12 patients paced in DDD mode for 3 months. Under autonomic blockade, effective refractory periods (ERPs) from the lateral right atrium (RA), RA appendage, RA septum, and coronary sinus–corrected sinus node recovery times (cSNRTs), as well as P-wave duration (PWD), and biatrial diameters were measured at baseline and 3 months. The VVI group was then programmed to DDD pacing and reevaluated after a further 3 months. After long-term VVI pacing, ERPs at all 4 atrial sites increased significantly in a nonuniform fashion in association with biatrial dilatation. PWD and cSNRTs also prolonged significantly. With the reestablishment of AV synchrony, ERPs, PWD, cSNRTs, and biatrial dimensions returned to baseline levels. In the 12 patients who underwent long-term DDD pacing from baseline, no significant changes in atrial electrophysiology or biatrial dimensions were demonstrated. Conclusions —Long-term loss of AV synchrony induced by VVI pacing is associated with atrial electrical remodeling, which is reversible after the reestablishment of AV synchrony with DDD pacing. This process may be partly responsible for the higher incidence of atrial fibrillation in patients undergoing VVI pacing compared with AV sequential pacing.
Association between 2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope
Authors: O Malysheva, M Pierer, U Wagner, M Wahle, U Wagner, C G Baerwald
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> In the present work, the frequency of inherited polymorphisms of the β2 adrenergic receptor (β2AR) gene and their association with rheumatoid arthritis (RA) as well as human leukocyte antigen (HLA)-DRB1 alleles was examined. <h3>Methods:</h3> An allele-specific polymerase chain reaction was used to determine the common variants of the β2AR at positions 16, 27 and 164 in patients with RA (n = 310) and ethnically matched healthy controls (n = 305) from Germany. HLA-DRB1 genotyping was performed by oligonucleotide hybridisation of enzymatically amplified DNA allowing low-resolution HLA-DRB1 genotyping comprising specificities DRB1*01 to DRB1*17. <h3>Results:</h3> Arginine (Arg) at codon 16 was present in 278 patients with RA (89.7%) compared to 202 controls (66.2%; odds ratio (OR) 4.43, 95% CI 2.81 to 7.02, p&lt;0.001). Homozygosity for Arg16 was found in 107 patients with RA (34.5%) compared to 14 controls (4.6%; OR 10.9, CI 5.9 to 20.5, p&lt;0.001). Stratifying patients for their HLA-DR status revealed that homozygosity for Arg16 exhibited the greatest risk for RA in combination with HLA-DRB1*04 (OR 17.1, 95% CI 1.71 to 414.4, p = 0.004). Interestingly, patients with the Arg16 allele have a younger mean (SD) age at disease onset compared to patients without Arg16 (46.1 (2.0) vs 53.1 (2.7) respectively, p&lt;0.05). Furthermore, 93.3% patients with homozygosity for Arg16 were positive for anti-cyclic citrullinated peptide (CCP) antibodies vs 75% patients with homozygosity for Gly16 (p&lt;0.05). <h3>Conclusion:</h3> There was a highly significant distortion between patients with RA and controls in the distribution of β2AR polymorphisms at codon 16, contributing (together with the HLA-DR alleles) to the genetic background of RA.
Angiotensin in progressive renal diseases
Authors: T Matsusaka, J Hymes, I Ichikawa
Journal: Journal of the American Society of Nephrology (1996)

Experimental studies indicate that Angll is involved in the process of tissue destruction in chronic renal diseases. This notion has been verified in a number of small-to large-scale clinical studies using angiotensin (ANG) I converting enzyme inhibitors (ACEI). Although the repertoire of the pathophysiologic cascade underlying the progressive destruction of renal tissue has continued to expand over recent years, from proteinuria and physical forces to growth factors and metalloproteinase disregulations, studies now suggest that Angll is involved in many, if not all, of these processes. Because these expanded pathophysiologic potentials of Angll are based primarily on observations in vitro, their significance in vivo, and in humans in particular, needs to be established. Recent studies in animals and humans indicate that the role of Angll in renal tissue destruction is subject to the modulation of multiple environmental and genetic factors, such as dietary habit and ACE genotype. Further delineation of the role of Angll in this respect for specific renal diseases and patients will enable us to design an efficient therapeutic intervention for this otherwise most complex problem of today's nephrology.
Overexpression of KIAA0101 Predicts High Stage, Early Tumor Recurrence, and Poor Prognosis of Hepatocellular Carcinoma
Authors: Ray-Hwang Yuan, Yung-Ming Jeng, Hung-Wei Pan, Fu-Chang Hu, Po-Lin Lai, Po-Huang Lee, Hey-Chi Hsu
Journal: Clinical Cancer Research (2007)

Abstract Purpose: KIAA0101 is a proliferating cell nuclear antigen–associated factor and involved in cell proliferation. This study is to elucidate its role in the progression, early tumor recurrence (ETR), and prognosis of hepatocellular carcinoma (HCC). Experimental Design: KIAA0101 mRNA was measured by reverse transcription-PCR in 216 resected, unifocal, primary HCCs and its protein in 164 cases by immunohistochemistry. Results: KIAA0101 mRNA was overexpressed in 131 (61%) HCCs, and protein was detected in 105 (64%). KIAA0101 mRNA overexpression correlated with higher tumor grade (P = 0.0001), higher tumor stage with vascular invasion and various extents of intrahepatic spread (P = 1 × 10−8), ETR (P = 1.8 × 10−6), and lower 5-year survival (P = 0.0026). Multivariate analysis confirmed that KIAA0101 overexpression was an independent risk factor associated with high-grade tumor (P = 0.0001), high-stage tumor (P &amp;lt; 0.0001), and ETR (P = 0.0052) and thus contributed to poor prognosis. KIAA0101 protein–positive tumor cells accumulated at the borders of tumor macrotrabeculae and were more abundant in tumor thrombi than in the main tumors. Hence, KIAA0101 may contribute to growth advantage and resistance to hypoxic insult. In this series, p53 mutation was detected in 93 of 184 (51%) HCCs. In both p53-mutated and non–p53-mutated HCCs, KIAA0101 overexpression correlated with higher vascular invasion (stages IIIA to IV; all Ps &amp;lt; 0.0001) and, accordingly, led to lower 5-year survival rates (P = 0.011 and 0.029, respectively). Conclusion: KIAA0101 correlates with enhanced metastatic potential and is a significant prognostic factor of HCC.
Negative regulation of BIK by the micro RNA125B interferes with macrophage apoptosis in rheumatoid arthritis
Authors: J. Presumey, I. Duroux-Richard, S. Fabre, Y.-M. Pers, G. Courties, C. Jorgensen, F. Apparailly
Journal: Annals of the Rheumatic Diseases (2010)

Cells from the mononuclear phagocyte system (MPS) act as systemic and local amplifiers that contribute to the progression of chronic inflammatory disorders such as rheumatoid arthritis (RA). …
Alcohol Intake and Colorectal Cancer: A Pooled Analysis of 8 Cohort Studies
Authors: Eunyoung Cho
Journal: Annals of Internal Medicine (2004)

Background: Epidemiologic studies have generally reported positive associations between alcohol consumption and risk for colorectal cancer. However, findings related to specific alcoholic beverages or different anatomic sites in the large bowel have been inconsistent. Objective: To examine the relationship of total alcohol intake and intake from specific beverages to the incidence of colorectal cancer and to evaluate whether other potential risk factors modify the association. Design: Pooled analysis of primary data from 8 cohort studies in 5 countries. Setting: North America and Europe. Participants: 489 979 women and men with no history of cancer other than nonmelanoma skin cancer at baseline. Measurements: Alcohol intake was assessed in each study at baseline by using a validated food-frequency questionnaire. Results: During a maximum of 6 to 16 years of follow-up across the studies, 4687 cases of colorectal cancer were documented. In categorical analyses, increased risk for colorectal cancer was limited to persons with an alcohol intake of 30 g/d or greater (approximately ≥ 2 drinks/d), a consumption level reported by 4% of women and 13% of men. Compared with nondrinkers, the pooled multivariate relative risks were 1.16 (95% CI, 0.99 to 1.36) for persons who consumed 30 to less than 45 g/d and 1.41 (CI, 1.16 to 1.72) for those who consumed 45 g/d or greater. No significant heterogeneity by study or sex was observed. The association was evident for cancer of the proximal colon, distal colon, and rectum. No clear difference in relative risks was found among specific alcoholic beverages. Limitations: The study included only one measure of alcohol consumption at baseline and could not investigate lifetime alcohol consumption, alcohol consumption at younger ages, or changes in alcohol consumption during follow-up. It also could not examine drinking patterns or duration of alcohol use. Conclusions: A single determination of alcohol intake correlated with a modest relative elevation in colorectal cancer rate, mainly at the highest levels of alcohol intake.
A subset of metastatic pancreatic ductal adenocarcinomas depends quantitatively on oncogenic Kras/Mek/Erk-induced hyperactive mTOR signalling
Authors: Bo Kong, Weiwei Wu, Tao Cheng, Anna Melissa Schlitter, Chengjia Qian, Philipp Bruns, Ziying Jian, Carsten Jäger, Ivonne Regel, Susanne Raulefs, Nora Behler, Martin Irmler, Johannes Beckers, Helmut Friess, Mert Erkan, Jens T Siveke, Andrea Tannapfel, Stephan A Hahn, Fabian J Theis, Irene Esposito, Jörg Kleeff, Christoph W Michalski
Journal: Gut (2015)

Oncogenic Kras-activated robust Mek/Erk signals phosphorylate to the tuberous sclerosis complex (Tsc) and deactivates mammalian target of rapamycin (mTOR) suppression in pancreatic ductal adenocarcinoma (PDAC); however, Mek and mTOR inhibitors alone have demonstrated minimal clinical antitumor activity.We generated transgenic mouse models in which mTOR was hyperactivated either through the Kras/Mek/Erk cascade, by loss of Pten or through Tsc1 haploinsufficiency. Primary cancer cells were isolated from mouse tumours. Oncogenic signalling was assessed in vitro and in vivo, with and without single or multiple targeted molecule inhibition. Transcriptional profiling was used to identify biomarkers predictive of the underlying pathway alterations and of therapeutic response. Results from the preclinical models were confirmed on human material.Reduction of Tsc1 function facilitated activation of Kras/Mek/Erk-mediated mTOR signalling, which promoted the development of metastatic PDACs. Single inhibition of mTOR or Mek elicited strong feedback activation of Erk or Akt, respectively. Only dual inhibition of Mek and PI3K reduced mTOR activity and effectively induced cancer cell apoptosis. Analysis of downstream targets demonstrated that oncogenic activity of the Mek/Erk/Tsc/mTOR axis relied on Aldh1a3 function. Moreover, in clinical PDAC samples, ALDH1A3 specifically labelled an aggressive subtype.These results advance our understanding of Mek/Erk-driven mTOR activation and its downstream targets in PDAC, and provide a mechanistic rationale for effective therapeutic matching for Aldh1a3-positive PDACs.