tbuckley/cabot-search huggingface dataset:
Association Between Imatinib-Resistant BCR-ABL Mutation-Negative Leukemia and Persistent Activation of LYN Kinase
Authors: Ji Wu, Feng Meng, Ling-Yuan Kong, Zhenghong Peng, Yunming Ying, William G. Bornmann, Bryant G. Darnay, Betty Lamothe, Hanshi Sun, Moshe Talpaz, Nicholas J. Donato
Journal: JNCI Journal of the National Cancer Institute (2008)

Imatinib is a tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). BCR-ABL mutations are associated with failure of imatinib treatment in many CML patients. LYN kinase regulates survival and responsiveness of CML cells to inhibition of BCR-ABL kinase, and differences in LYN regulation have been found between imatinib-sensitive and -resistant CML cell lines.We evaluated cells from 12 imatinib-resistant CML patients with mutation-negative BCR-ABL and from six imatinib-sensitive patients who discontinued therapy because of imatinib intolerance. Phosphorylation of BCR-ABL and LYN was assessed in patient cells and cell lines by immunoblotting with activation state-specific antibodies, co-immunoprecipitation studies, and mass spectroscopy analysis of phosphopeptides. Cell viability, caspase activation, and apoptosis were also measured. Mutations were analyzed by sequencing. The effect of silencing LYN with short interfering RNAs (siRNAs) or reducing activation by treatment with tyrosine kinase inhibitors was evaluated in cell lines and patient cells.Imatinib treatment suppressed LYN phosphorylation in cells from imatinib-sensitive CML patients and imatinib-sensitive cell lines. Imatinib treatment blocked BCR-ABL signaling but did not suppress LYN phosphorylation in cells from imatinib-resistant patients, and persistent activation of LYN kinase was not associated with mutations in LYN kinase or its carboxyl-terminal regulatory domains. Unique LYN phosphorylation sites (tyrosine-193 and tyrosine-459) and associated proteins (c-Cbl and p80) were identified in cells from imatinib-resistant patients. Reducing LYN expression (siRNA) or activation (dasatinib) was associated with loss of cell survival and cytogenetic or complete hematologic responses in imatinib-resistant disease.LYN activation was independent of BCR-ABL in cells from imatinib-resistant patients. Thus, LYN kinase may be involved in imatinib resistance in CML patients with mutation-negative BCR-ABL and its direct inhibition is consistent with clinical responses in these patients.
Wired but not WEIRD: The promise of the Internet in reaching more diverse samples
Authors: Samuel D. Gosling, Carson J. Sandy, Oliver P. John, Jeff Potter
Journal: Behavioral and Brain Sciences (2010)

Can the Internet reach beyond the U. S. college samples predominant in social science research? A sample of 564,502 participants completed a personality questionnaire online. We found that 19% were not from advanced economies; 20% were from non-Western societies; 35% of the Western-society sample were not from the United States; and 66% of the U. S. sample were not in the 18-22 (college) age group.
Update in Diffuse Parenchymal Lung Diseases 2005
Authors: Fernando J. Martinez, Michael P. Keane
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

CLINICAL ADVANCES A number of publications have shed light on important clinical concepts surrounding the clinical evaluation and management of diffuse parenchymal lung diseases (DPLDs). These include approaches to idiopathic interstitial pneumonias (IIPs), including nonspecific interstitial pneumonia (NSIP) and idiopathic pulmonary fibrosis (IPF; idiopathic usual interstitial pneumonia [UIP]), connective tissue–associated DPLD, hypersensitivity pneumonitis (HP), and lymphangioleiomyomatosis (LAM). IIPs A series of sentinel observations have addressed diagnostic issues, staging approaches, unique phenotypes, and management strategies for IIPs. Diagnostic approach. The approach to diagnosis in patients with DPLDs has continued to evolve over the past decade. A recent centennial review described the major impact of highresolution computed tomography (HRCT) in guiding the diagnostic approach to patients with suspected IIP (1). It is evident that stereotypical imaging features have been described for many DPLDs, including some of the IIPs (2). The diagnostic accuracy of the radiological features of UIP has been demonstrated in well-designed clinical studies (3–5). Despite these data, there remains diagnostic confusion regarding the separation of UIP from other IIPs, particularly NSIP (6). On the other hand, increasing data have suggested that predominance of ground-glass opacity with no honeycombing is more common in NSIP. In a recent series, such a pattern was seen in 96% of patients with NSIP and 59% of patients with UIP (7). Unfortunately, the overall diagnostic accuracy of HRCT for separating these two disorders was 70% in this series. The contrast between expert and less experienced radiologists in applying HRCT criteria to the diagnosis of IPF has recently been reported in data from a landmark clinical therapeutic trial (8). As part of this trial, HRCT scans were interpreted by clinical site radiologists and an expert radiology core using predefined criteria. The core radiologists agreed with a diagnosis of IPF in 99% of those diagnosed by site radiologists; little difference was found if the clinical site was an “academic” center or a community-based practice. A survey of American College of Chest Physician members (52.6% responses to the survey) suggested that 67% of respondents accepted HRCT diagnosis for IPF (9). Interestingly, one investigative group has demonstrated that interaction between expert clinicians and radiologists improves the interobserver agreement of the former in evaluating patients with IIPs (10). It is evident that a consensus is developing that typical features of UIP in the appropriate clinical setting can be used to accurately diagnose IPF. In other IIPs, particularly
Effect of Anti-IgE Therapy in Patients with Peanut Allergy
Authors: Donald Y.M. Leung, Hugh A. Sampson, John W. Yunginger, A. Wesley Burks, Lynda C. Schneider, Cornelis H. Wortel, Frances M. Davis, John D. Hyun, William R. Shanahan
Journal: New England Journal of Medicine (2003)

Peanut-induced anaphylaxis is an IgE-mediated condition that is estimated to affect 1.5 million people and cause 50 to 100 deaths per year in the United States. TNX-901 is a humanized IgG1 monoclonal antibody against IgE that recognizes and masks an epitope in the CH3 region of IgE responsible for binding to the high-affinity Fcε receptor on mast cells and basophils.
Alcohol consumption, cigarette smoking and risk of subtypes of oesophageal and gastric cancer: a prospective cohort study
Authors: J Steevens, L J Schouten, R A Goldbohm, P A van den Brandt
Journal: Gut (2009)

<h3>Objective:</h3> Alcohol consumption and cigarette smoking may be differentially associated with oesophageal squamous cell carcinoma (OSCC), oesophageal adenocarcinoma (OAC), gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). However, because this was based on retrospective studies, these hypotheses were examined in a prospective cohort. <h3>Methods:</h3> The prospective Netherlands Cohort Study consists of 120 852 participants who completed a baseline questionnaire on diet and other cancer risk factors in 1986. After 16.3 years of follow-up, 107 OSCC, 145 OAC, 164 GCA and 491 GNCA cases were available for analysis using Cox proportional hazards models and the case–cohort approach. <h3>Results:</h3> The multivariable adjusted incidence rate ratio (RR) for OSCC was 4.61 (95% CI 2.24 to 9.50) for ⩾30 g ethanol/day compared with abstainers (p trend &lt;0.001), while no associations with alcohol were found for OAC, GCA or GNCA. Compared with never smokers, current smokers had RRs varying from 1.60 for GCA to 2.63 for OSCC, and were statistically significant or borderline statistically significant. Frequency, duration and pack-years of smoking were independently associated with risk of all four cancers. A positive interaction was found between alcohol consumption and smoking status regarding OSCC risk. The RR for current smokers who consumed &gt;15 g/day of ethanol was 8.05 (95% CI 3.89 to 16.60; p interaction = 0.65), when compared with never smokers who consumed &lt;5 g/day of ethanol. <h3>Conclusions:</h3> This prospective study found alcohol consumption to be associated with increased risk of only OSCC. Cigarette smoking was associated with risk of all four cancers.
Glucose Intolerance and Cardiometabolic Risk in Adolescents Exposed to Maternal Gestational Diabetes
Authors: Wing Hung Tam, Ronald Ching Wan Ma, Xilin Yang, Albert Martin Li, Gary Tin Choi Ko, Alice Pik Shan Kong, Terence Tzu Hsi Lao, Michael Ho Ming Chan, Christopher Wai Kei Lam, Juliana Chung Ngor Chan
Journal: Diabetes Care (2010)

Adolescent offspring of women with a history of gestational diabetes (GD) were evaluated for their cardiometabolic risks at a mean age of 15 years.One hundred and twenty-nine adolescents who were assessed for their cardiometabolic risks at 8 years of age were reassessed at 15 years of age.Adolescent offspring of mothers with GD had similar blood pressure, plasma lipid profile, and a rate of abnormal glucose tolerance as control subjects. In utero hyperinsulinemia was associated with a 17-fold increase in metabolic syndrome and a 10-fold increase in overweight at adolescence, independent of birth weight, Tanner stage, maternal GD status, and mother's BMI.In utero environment of hyperinsulinemia, irrespective of the degree of maternal GD, was associated with increased risk of overweight and metabolic syndrome during early adolescence in the offspring.
Role of SIRT1 in regulation of epithelial-to-mesenchymal transition in oral squamous cell carcinoma metastasis
Authors: I-Chieh Chen, Wei-Fan Chiang, Hsin-Hsiu Huang, Pei-Fen Chen, Ying-Ying Shen, Hung-Che Chiang
Journal: Molecular Cancer (2014)

The epithelial-to-mesenchymal transition (EMT) process results in a loss of cell-cell adhesion, increased cell mobility, and is crucial for enabling the metastasis of cancer cells. Recently, the enzyme SIRT1 has been implicated in a variety of physiological processes; however, its role in regulating oral cancer metastasis and EMT is not fully elucidated. Here, we propose a mechanism by which the enzyme sirtuin1 (SIRT1) regulates the EMT process in oral cancer by deacetylating Smad4 and repressing the effect of TGF-β signaling on matrix metalloproteinase-7 (MMP7). The roles of SIRT1 in tumor cell migration/invasion and metastasis to the lungs were investigated using the Boyden chamber assay and orthotopic injections, respectively. RNA interference was used to knockdown either SIRT1 or Smad4 expression in oral squamous cell carcinoma (OSCC) cell lines. Immunoblotting, zymographic assays, and co-immunoprecipitation were used to examine the effects of SIRT1 overexpression on MMP7 expression and activity, as well as on SIRT1/ Smad4 interaction. We found that compared with normal human oral keratinocytes (HOKs), SIRT1 was underexpressed in OSCC cells, and also in oral cancer tissues obtained from 14 of 21 OSCC patients compared with expression in their matched normal tissues. Overexpression of SIRT1 inhibited migration of OSCC cells in vitro, as well as their metastasis to the lung in vivo. Furthermore, up-regulation of SIRT1 in metastatic OSCCs significantly inhibited the migration and invasion abilities of OSCC cells, while concomitantly increasing the expression of E-cadherin, and decreasing the expressions of mesenchymal markers. We also identified Smad4, a TGF-β-activated transcription factor, as a direct target protein for SIRT1. Overexpression of SIRT1 in OSCC cells led to decreased levels of acetylated Smad4, and inhibition of TGF-β-induced signaling. By associating and deacetylating Smad4, SIRT1 enzyme can influence MMP7 expression, MMP enzyme activity, and consequently, cell migration, invasion, and tumor metastasis in OSCCs. These findings provide a valuable insight into the potential role of the SIRT1 enzyme in regulating cell migration and invasion in oral squamous cell carcinoma. Our findings suggest the SIRT1/Smad4/MMP7 pathway as a target for oral cancer driven by EMT.
RNA interference against cancer/testis genes identifies dual specificity phosphatase 21 as a potential therapeutic target in human hepatocellular carcinoma
Authors: Qing Deng, Kun-Yu Li, Hui Chen, Ji-Hong Dai, Yang-Yang Zhai, Qun Wang, Niu Li, Yu-Ping Wang, Ze-Guang Han
Journal: Hepatology (2013)

Cancer/testis (CT) antigens have been considered therapeutic targets for treating cancers. However, a central question is whether their expression contributes to tumorigenesis or if they are functionally irrelevant by-products derived from the process of cellular transformation. In any case, these CT antigens are essential for cancer cell survival and may serve as potential therapeutic targets. Recently, the cell-based RNA interference (RNAi) screen has proven to be a powerful approach for identifying potential therapeutic targets. In this study we sought to identify new CT antigens as potential therapeutic targets for human hepatocellular carcinoma (HCC), and 179 potential CT genes on the X chromosome were screened through a bioinformatics analysis of gene expression profiles. Then an RNAi screen against these potential CT genes identified nine that were required for sustaining the survival of Focus and PLC/PRF/5 cells. Among the nine genes, the physiologically testis-restricted dual specificity phosphatase 21 (DUSP21) encoding a dual specificity phosphatase was up-regulated in 39 (33%) of 118 human HCC specimens. Ectopic DUSP21 had no obvious impact on proliferation and colony formation in HCC cells. However, DUSP21 silencing significantly suppressed cell proliferation, colony formation, and in vivo tumorigenicity in HCC cells. The administration of adenovirus-mediated RNAi and an atelocollagen/siRNA mixture against endogenous DUSP21 significantly suppressed xenograft HCC tumors in mice. Further investigations showed that DUSP21 knockdown led to arrest of the cell cycle in G1 phase, cell senescence, and expression changes of some factors with functions in the cell cycle and/or senescence. Furthermore, the antiproliferative role of DUSP21 knockdown is through activation of p38 mitogen-activated protein kinase in HCC. Conclusion : DUSP21 plays an important role in sustaining HCC cell proliferation and may thus act as a potential therapeutic target in HCC treatment. (Hepatology 2014;59:518–530)
Enhancement of Benzo[&lt;italic&gt;a&lt;/italic&gt;]pyrene-Induced Sister Chromatid Exchanges in Lymphocytes From Cigarette Smokers Occupationally Exposed to Asbestos&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: K T Kelsey, D C Christiani, J B Little
Journal: JNCI Journal of the National Cancer Institute (1986)

The frequencies of base-line and benzo[a]pyrene [(BP) CAS 50-38-8]-induced sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes from 22 male asbestos-exposed workers and 10 nonexposed workers of comparable age. A clear association between cigarette smoking and asbestos exposure in the sensitivity of lymphocytes to BP was observed. Among asbestos-exposed workers, lymphocytes from those who smoked cigarettes were significantly more susceptible to the induction of SCE by in vitro exposure to BP (P = .01) than were lymphocytes from nonsmokers. Active smoking elevated the base-line SCE frequency in both asbestos-exposed and nonexposed workers (P = .001), and an interaction between smoking and asbestos in the production of base-line SCE was suggested (P = .07). Asbestos exposure alone was not associated with an enhanced susceptibility to the induction of SCE by BP or with an elevation of base-line SCE. Increased age was associated with an increase in SCE inducibility by BP (P = .01), and a history of smoking was marginally associated with SCE inducibility by BP (P = .07). These findings support the hypothesis that an increased susceptibility of asbestos-exposed individuals to polyaromatic hydrocarbon- induced cancer results from an enhanced sensitivity to the induction of genetic damage rather than to an asbestos-induced differential cellular metabolic capacity.
Identification of cyclin A as a molecular target of antinuclear antibodies (ANA) in hepatic and non-hepatic autoimmune disease
Authors: Christian P. Strassburg, Britta Alex, auFréderique Zindy, Guido Gerken, Birgit Lüttig, Karl-hermann Meyer zum Büschenfelde, Christian Bréchot, Michael P. Manns
Journal: Journal of Hepatology (1996)
Capillary, Interstitial, and Cell Membrane Barriers to Blood-Tissue Transport of Potassium and Rubidium in Mammalian Skeletal Muscle
Authors: R. M. SHEEHAN, E. M. RENKIN
Journal: Circulation Research (1972)

Blood-tissue transport of 42 K, 86 Rb, and 22 Na was studied in perfused gracilis muscles of dogs to ascertain the influence of capillary wall, interstitial space, and muscle cell membranes on overall transport kinetics. Single-injection and continuous-infusion techniques were used, with T-1824 or 51 Cr-hemoglobin as nondiffusible references. Results were as follows: (1) Extraction ( E ) of the diffusible solutes was incomplete even in the earliest samples of venous outflow. (2) E Rb equaled E K in the first few samples, but later, as both declined, the ratio of E Rb to E K became less than one; stable ratios between 0.6 and 0.8 were established in different experiments. (3) E Na was initially slightly less than E Rb or E K but declined much more sharply in successive samples. (4) Steadystate E Rb and E K decreased with increasing blood flow but maintained a constant ratio. Vasomotion sometimes changed E Rb and E K but had little effect on their ratio. Local anesthetics (procaine or cocaine) brought the ratio of E Rb to E K closer to one. Analysis in terms of capillary and interstitial barriers, which do not discriminate between K, Rb, or Na, in series with a muscle cell membrane barrier, which does, leads to the following conclusions. (1) For K, the nondiscriminating barrier (mainly capillary wall) offers about 70% of the total resistance to transport and the discriminating barrier (cell membrane) about 30%. (2) For Rb, each barrier offers half the total resistance. (3) The resting muscle cell membrane is 2.5 times more permeable to K than to Rb. Local anesthetics reduce cell permeability to both ions and decrease this ratio. (4) For Na, resistance at the capillary wall is about 1.3 times that for K or Rb. Resistance at the cell membrane is, of course, very much greater.
No serological evidence of Rickettsia helvetica infection in Scandinavian sarcoidosis patients
Authors: A. Planck, A. Eklund, J. Grunewald, S. Vene
Journal: European Respiratory Journal (2004)

Many agents have been suggested to elicit sarcoidosis, and, recently, an association was presented between this disease and the bacterium Rickettsia helvetica. The aim of this study was to investigate if serological support for such an association could be detected. Sera from 20 well-characterised sarcoidosis patients were investigated for anti-rickettsial immunoglobulin G antibodies with a micro-immunofluorescence technique. R. helvetica, R. conorii and R. typhi served as antigens. In conclusion, none of the investigated sera displayed detectable titres of anti-rickettsial immunoglobulin G antibodies. Thus, the current study does not support an association between rickettsia and sarcoidosis.
Corrigendum to: “Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health” [J Hepatol 2012;57:133–140]
Authors: Karin Dilger, Simon Hohenester, Ursula Winkler-Budenhofer, Barbara A.J. Bastiaansen, Frank G. Schaap, Christian Rust, Ulrich Beuers
Journal: Journal of Hepatology (2013)
Health Care Use of Long-Term Survivors of Childhood Cancer: The British Childhood Cancer Survivor Study
Authors: Cornelia E. Rebholz, Raoul C. Reulen, Andrew A. Toogood, Clare Frobisher, Emma R. Lancashire, David L. Winter, Claudia E. Kuehni, Michael M. Hawkins
Journal: Journal of Clinical Oncology (2011)

Survivors of childhood cancer are at high risk of chronic conditions, but few studies investigated whether this translates into increased health care utilization. We compared health care service utilization between childhood cancer survivors and the general British population and investigated potential risk factors.We used data from the British Childhood Cancer Survivor Study, a population-based cohort of 17,981 individuals diagnosed with childhood cancer (1940-1991) and surviving ≥ 5 years. Frequency of talks to a doctor, hospital outpatient visits, and day-patient and inpatient hospitalizations were ascertained by questionnaire in 10,483 survivors and were compared with the General Household Survey 2002 data by using logistic regression.Among survivors, 16.5% had talked to a doctor in the last 2 weeks, 25.5% had attended the outpatient department of a hospital in the last 3 months, 11.9% had been hospitalized as a day patient in the last 12 months, and 9.8% had been hospitalized as an inpatient in the last 12 months. Survivors had talked slightly more often to a doctor than the general population (odds ratio [OR], 1.2; 95% CI, 1.1 to 1.3) and experienced increased hospital outpatient visits (OR, 2.5; 95% CI, 2.3 to 2.8), day-patient hospitalizations (OR, 1.4; 95% CI, 1.3 to 1.6) and inpatient hospitalizations (OR, 1.9; 95% CI, 1.7 to 2.2). Survivors of Hodgkin's lymphoma, neuroblastoma, and Wilms tumor had the highest ORs for day-patient care, whereas survivors of CNS tumors and bone sarcomas had the highest OR for outpatient and inpatient care. The OR of health care use did not vary significantly with age of survivor.We have quantified how excess morbidity experienced by survivors of childhood cancer translates into increased use of health care facilities.
Involvement of CD56 (NKH-1/Leu-19 antigen) as an adhesion molecule in natural killer-target cell interaction.
Authors: T Nitta, H Yagita, K Sato, K Okumura
Journal: The Journal of Experimental Medicine (1989)

The CD56 differentiation antigen, recognized by anti-Leu-19 and NKH-1 mAbs, is a 200-220-kD glycoprotein that is expressed predominantly on human NK cells and a minor subset of T lymphocytes mediating MHC-unrestricted cytotoxicity. The recent finding that CD56 is an isoform of the neural cell adhesion molecule (N-CAM) prompted us to examine the adhesive function of CD56 in the NK-target cell interaction. Synergistic inhibitory effects of anti-CD56 mAbs with anti-LFA-1 and/or anti-LFA-3 mAbs were demonstrated on NK cell-mediated cytotoxicity and on NK cell binding to target cells only when the target cells also express CD56. These findings indicate that CD56 on NK cells can serve as the third pathway of cell adhesion other than those mediated by the CD2/LFA-3 and LFA-1/ICAM-1 interactions, and is involved in NK cell cytotoxicity when interacting with the cells bearing N-CAM.