tbuckley/cabot-search huggingface dataset:
Lipid Testing Among Patients With Diabetes Who Receive Diabetes Care From Primary Care Physicians
Authors: Mark W. Massing, Nancy S. Henley, Lori Carter-Edwards, Anna P. Schenck, Ross J. Simpson
Journal: Diabetes Care (2003)

OBJECTIVE—To identify factors related to lipid testing among patients with diabetes who receive diabetes care from primary care physicians. RESEARCH DESIGN AND METHODS—North Carolina Medicare claims were used to identify individuals with diabetes who received diabetes care from primary care physicians. Lipid testing was related to sociodemographic characteristics, comorbid conditions, physician specialty, and mortality. RESULTS—Based on Medicare claims from July 1997 through June 1999, 13,660 diabetic North Carolina residents with Medicare, 65–75 years of age, had received HbA1c testing from a single primary care physician during at least three of four consecutive 6-month time intervals. During these 2 years, 31% had no lipid profile and 24% had only one lipid profile. Caucasians were 1.6 times more likely than African Americans to receive lipid profiles. Patients not receiving state Medicare assistance were 1.4 times more likely to have a lipid profile than the presumably lower-income patients receiving assistance. Patients with stroke and heart failure were less likely to receive lipid profiles. Those with no lipid profile were almost twice as likely to die from cardiovascular disease than those with at least two lipid profiles. CONCLUSIONS—Adherence to lipid testing recommendations by primary care physicians for elderly patients with diabetes has much room for improvement. The most vulnerable patients (African Americans, the economically disadvantaged, and the medically complex) are the least likely to receive lipid testing.
Idiopathic chronic eosinophilic pneumonia and asthma: how do they influence each other?
Authors: E. Marchand, B. Etienne-Mastroianni, P. Chanez, D. Lauque, P. Leclerc, J.F. Cordier
Journal: European Respiratory Journal (2003)

Since idiopathic chronic eosinophilic pneumonia (ICEP) and asthma are frequently associated, their possible reciprocal influence on clinical presentation and evolution were investigated. The clinical and follow-up features of 53 cases of ICEP, of which 41 (77%) had asthma, were reviewed retrospectively. Asthma preceded the diagnosis of ICEP in 26 patients, was contemporaneous in eight patients, and developed 17 +/- 12 months after ICEP in seven patients. Presentation of ICEP was similar in asthmatics and nonasthmatics with the exception of a higher level of total immunoglobulin E in the former group. Patients with asthma at the time of diagnosis of ICEP were more likely to remain free of relapse of ICEP (56 versus 23%) and had a lower number of relapses per year of follow-up (median 0 versus 0.24). Moreover, they were treated more frequently with long-term inhaled corticosteroids (88 versus 31%) at last follow-up. Asthma got worse after the diagnosis of ICEP and frequently required long-term oral corticosteroids. To conclude, among patients with idiopathic chronic eosinophilic pneumonia, asthmatics have a lower frequency of relapse than nonasthmatics, possibly because of a higher use of inhaled corticosteroids. The occurrence of idiopathic chronic eosinophilic pneumonia in asthmatics is often associated with the development of severe asthma.
Antifibrotic property of brain natriuretic peptide in cardiac fibroblasts: Cross-talk action with endothelin-1 and tumor necrosis factor on the induction of matrix metalloproteinases
Authors: Toshihiro Tsuruda, Guido Boerrigter, Brenda K. Huntley, Josh A. Noser, Alessandro Cataliotti, John C. Burnett
Journal: Journal of the American College of Cardiology (2003)
Systemic Cancer Therapy with a Small Molecule Agonist of Toll-like Receptor 7 Can Be Improved by Circumventing TLR Tolerance
Authors: Carole Bourquin, Christian Hotz, Daniel Noerenberg, Andreas Voelkl, Simon Heidegger, Laurin C. Roetzer, Bettina Storch, Nadja Sandholzer, Cornelia Wurzenberger, David Anz, Stefan Endres
Journal: Cancer Research (2011)

Topical application of small molecule Toll-like receptor 7 (TLR7) agonists is highly effective for the treatment of skin tumors, whereas their systemic application has been largely unsuccessful for cancer therapy. One reason may be that repeated systemic application of TLR ligands can induce a state of immune unresponsiveness, termed TLR tolerance. We show here that a single injection of the TLR7 agonist R848 in mice induces a short period of increased response to TLR stimulation followed by a state of hyporesponsiveness lasting several days. This state is characterized by inhibited secretion of the key cytokines interleukin (IL)-12p70 and IL-6 as well as by a block in IFN-α production. We show for the first time that at the cellular level, TLR7 tolerance occurs in both plasmacytoid and myeloid dendritic cells, two cell populations that play a critical role in the initiation and amplification of antitumor immune responses. We further show that TLR7 tolerance in plasmacytoid dendritic cells is accompanied by downregulation of the adaptor protein IL-1 receptor-associated kinase 1. On the basis of these findings, we have designed a novel strategy for the treatment of tumors by using cycles of repeated R848 injections separated by treatment-free intervals. We show in CT26 tumor-bearing mice that this protocol circumvents TLR7 tolerance and improves the efficacy of cancer immunotherapy.
Expressed sequence tag profiling identifies developmental and anatomic partitioning of gene expression in the mouse prostate
Authors: Denise E Abbott, Colin Pritchard, Nigel J Clegg, Camari Ferguson, Ruth Dumpit, Robert A Sikes, Peter S Nelson
Journal: Genome biology (2003)

The prostate gland is an organ with highly specialized functional attributes that serves to enhance the fertility of mammalian species. Much of the information pertaining to normal and pathological conditions affecting the prostate has been obtained through extensive developmental, biochemical and genetic analyses of rodent species. Although important insights can be obtained through detailed anatomical and histological assessments of mouse and rat models, further mechanistic explanations are greatly aided through studies of gene and protein expression.
Cyclooxygenase-2 Inhibition Inhibits c-Met Kinase Activity and Wnt Activity in Colon Cancer
Authors: Jurriaan B. Tuynman, Louis Vermeulen, Elles M. Boon, Kristel Kemper, Aeilko H. Zwinderman, Maikel P. Peppelenbosch, Dirk J. Richel
Journal: Cancer Research (2008)

Activity of receptor tyrosine kinases (RTK) in colorectal cancer (CRC) is associated with enhanced tumor growth and a poorer prognosis. In addition, cyclooxygenase-2 (COX-2) expression contributes to tumor growth and invasion. COX-2 inhibitors exhibit important anticarcinogenic potential against CRC, but the molecular mechanism underlying this effect and the relation with RTK signaling remain the subject of intense research effort. Therefore, the rapid effects of COX-2 inhibition in CRC on the complement of all cellular kinases were investigated using a kinase substrate peptide array, Western blotting, transfection, small interfering RNA assays, and CRC cell lines. The resulting alterations in the kinome profile revealed that celecoxib, a selective COX-2 inhibitor, impairs phosphorylation of substrates for the RTKs c-Met and insulin-like growth factor receptor, resulting in decreased downstream signaling. The decrease in c-Met activation is accompanied with an increase in glycogen synthase kinase 3beta kinase activity together with a rapid increase in phosphorylation of beta-catenin. In agreement, a significant reduction of beta-catenin-T-cell factor-dependent transcription is observed both with celecoxib and selective inhibition of c-Met phosphorylation by small molecules. Hence, corepression of c-Met-related and beta-catenin-related oncogenic signal transduction seems a major effector of celecoxib in CRC, which provides a rationale to use c-Met inhibitors and celecoxib analogous to target c-Met and Wnt signaling in a therapeutic setting for patients with CRC.
Right Heart Failure Secondary to Compression of the Right Pulmonary Artery by a Large Proximal Aortic Aneurysm
Authors: Tomonobu Abe, Yosuke Kamikubo, Tetsuyoshi Taneichi, Takafumi Terada, Jyunya Sugiura, Takahisa Sakurai, Naoya Tsuboi, Hajime Sakurai
Journal: Circulation (2013)
Randomized, Phase III Study of Gemcitabine or Erlotinib Maintenance Therapy Versus Observation, With Predefined Second-Line Treatment, After Cisplatin-Gemcitabine Induction Chemotherapy in Advanced Non–Small-Cell Lung Cancer
Authors: Maurice Pérol, Christos Chouaid, David Pérol, Fabrice Barlési, Radj Gervais, Virginie Westeel, Jacky Crequit, Hervé Léna, Alain Vergnenègre, Gérard Zalcman, Isabelle Monnet, Hervé Le Caer, Pierre Fournel, Lionel Falchero, Michel Poudenx, Fabien Vaylet, Céline Ségura-Ferlay, Mojgan Devouassoux-Shisheboran, Miquel Taron, Bernard Milleron
Journal: Journal of Clinical Oncology (2012)

This phase III study investigated whether continuation maintenance with gemcitabine or switch maintenance with erlotinib improves clinical outcome compared with observation in patients with advanced non-small-cell lung cancer (NSCLC) whose disease was controlled after cisplatin-gemcitabine induction chemotherapy.Four hundred sixty-four patients with stage IIIB/IV NSCLC without tumor progression after four cycles of cisplatin-gemcitabine were randomly assigned to observation or to gemcitabine (1,250 mg/m(2) days 1 and 8 of a 3-week cycle) or daily erlotinib (150 mg/day) study arms. On disease progression, patients in all three arms received pemetrexed (500 mg/m(2) once every 21 days) as predefined second-line therapy. The primary end point was progression-free survival (PFS).PFS was significantly prolonged by gemcitabine (median, 3.8 v 1.9 months; hazard ratio [HR], 0.56; 95% CI, 0.44 to 0.72; log-rank P < .001) and erlotinib (median, 2.9 v 1.9 months; HR, 0.69; 95% CI, 0.54 to 0.88; log-rank P = .003) versus observation; this benefit was consistent across all clinical subgroups. Both maintenance strategies resulted in a nonsignificant improvement in overall survival (OS); patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit. Exploratory analysis showed that magnitude of response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated with no unexpected adverse events.Gemcitabine continuation maintenance or erlotinib switch maintenance significantly reduces disease progression in patients with advanced NSCLC treated with cisplatin-gemcitabine as first-line chemotherapy. Response to induction chemotherapy may affect OS only for continuation maintenance.
Expression of RASSF1A, an Epigenetically Silenced Tumor Suppressor, Overcomes Resistance to Apoptosis Induction by Interferons
Authors: Frederic J. Reu, Douglas W. Leaman, Ratan R. Maitra, Soo In Bae, Leonid Cherkassky, Mark W. Fox, Donald R. Rempinski, Normand Beaulieu, A. Robert MacLeod, Ernest C. Borden
Journal: Cancer Research (2006)

Abstract Resistance of human renal cell carcinoma (RCC) and melanoma to the apoptosis-inducing effects of IFNs was postulated to result from epigenetic silencing of genes by DNA methylation, a common feature of human cancers. To reverse silencing, 5-AZA-deoxycytidine (5-AZA-dC) or selective depletion of DNA methyltransferase 1 (DNMT1) by phosphorothioate oligonucleotide antisense (DNMT1 AS) were employed in cells resistant (&amp;lt;5% terminal deoxynucleotidyl transferase–mediated nick-end labeling positive) to apoptosis induction by IFN-α2 and IFN-β (ACHN, SK-RC-45, and A375). 5-AZA-dC and DNMT1 AS similarly depleted available DNMT1 protein and, at doses that did not cause apoptosis alone, resulted in apoptotic response to IFNs. The proapoptotic tumor suppressor RASSF1A was reactivated by DNMT1 inhibitors in all three cell lines. This was associated with demethylation of its promoter region. IFNs augmented RASSF1A protein expression after reactivation by DNMT1 inhibition. In IFN-sensitive WM9 melanoma cells, expression of RASSF1A was constitutive but also augmented by IFNs. RASSF1A small interfering RNA reduced IFN-induced apoptosis in WM9 cells and in DNMT1-depleted ACHN cells. Conversely, lentiviral expression of RASSF1A but not transduction with empty virus enabled IFN-induced apoptosis. IFN induced tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and TRAIL-neutralizing antibody inhibited apoptotic response to IFN in RASSF1A-expressing ACHN cells. Accordingly, RASSF1A markedly sensitized to recombinant TRAIL. Normal kidney epithelial cells, although expressing RASSF1A, did not undergo apoptosis in response to IFN or TRAIL but had &amp;gt;400-fold higher TRAIL decoy receptor 1 expression than transduced ACHN cells (real-time reverse transcription-PCR). Results identified RASSF1A as regulated by IFNs and participating in IFN-induced apoptosis at least in part by sensitization to TRAIL. (Cancer Res 2006; 66(5): 2785-93)
Environmental Public Health Tracking of Childhood Asthma Using California Health Interview Survey, Traffic, and Outdoor Air Pollution Data
Authors: Michelle Wilhelm, Ying-Ying Meng, Rudolph P. Rull, Paul English, John Balmes, Beate Ritz
Journal: Environmental Health Perspectives (2008)

Despite extensive evidence that air pollution affects childhood asthma, state-level and national-level tracking of asthma outcomes in relation to air pollution is limited.Our goals were to evaluate the feasibility of linking the 2001 California Health Interview Survey (CHIS), air monitoring, and traffic data; estimate associations between traffic density (TD) or outdoor air pollutant concentrations and childhood asthma morbidity; and evaluate the usefulness of such databases, linkages, and analyses to Environmental Public Health Tracking (EPHT).We estimated TD within 500 feet of residential cross-streets of respondents and annual average pollutant concentrations based on monitoring station measurements. We used logistic regression to examine associations with reported asthma symptoms and emergency department (ED) visits/hospitalizations.Assignment of TD and air pollution exposures for cross-streets was successful for 82% of children with asthma in Los Angeles and San Diego, California, Counties. Children with asthma living in high ozone areas and areas with high concentrations of particulate matter < 10 microm in aerodynamic diameter experienced symptoms more frequently, and those living close to heavy traffic reported more ED visits/hospitalizations. The advantages of the CHIS for asthma EPHT include a large and representative sample, biennial data collection, and ascertainment of important socio-demographic and residential address information. Disadvantages are its cross-sectional design, reliance on parental reports of diagnoses and symptoms, and lack of information on some potential confounders.Despite limitations, the CHIS provides a useful framework for examining air pollution and childhood asthma morbidity in support of EPHT, especially because later surveys address some noted gaps. We plan to employ CHIS 2003 and 2005 data and novel exposure assessment methods to re-examine the questions raised here.
Inhibition of MEK and PI3K/mTOR Suppresses Tumor Growth but Does Not Cause Tumor Regression in Patient-Derived Xenografts of RAS-Mutant Colorectal Carcinomas
Authors: Giorgia Migliardi, Francesco Sassi, Davide Torti, Francesco Galimi, Eugenia R. Zanella, Michela Buscarino, Dario Ribero, Andrea Muratore, Paolo Massucco, Alberto Pisacane, Mauro Risio, Lorenzo Capussotti, Silvia Marsoni, Federica Di Nicolantonio, Alberto Bardelli, Paolo M. Comoglio, Livio Trusolino, Andrea Bertotti
Journal: Clinical Cancer Research (2012)

Gene mutations along the Ras pathway (KRAS, NRAS, BRAF, PIK3CA) occur in approximately 50% of colorectal cancers (CRC) and correlate with poor response to anti-EGF receptor (EGFR) therapies. We assessed the effects of mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) and phosphoinositide 3-kinase (PI3K)/mTOR inhibitors, which neutralize the major Ras effectors, in patient-derived xenografts from RAS/RAF/PIK3CA-mutant metastatic CRCs (mCRC).Forty mCRC specimens harboring KRAS, NRAS, BRAF, and/or PIK3CA mutations were implanted in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Each xenograft was expanded into four treatment arms: placebo, the MEK inhibitor AZD6244, the PI3K/mTOR inhibitor, BEZ235, or AZD6244 + BEZ235. Cases initially treated with placebo crossed over to AZD6244, BEZ235, and the anti-EGFR monoclonal antibody cetuximab.At the 3-week evaluation time point, cotreatment of established tumors with AZD6244 + BEZ235 induced disease stabilization in the majority of cases (70%) but did not lead to overt tumor regression. Monotherapy was less effective, with BEZ235 displaying higher activity than AZD6244 (disease control rates, DCRs: AZD6244, 27.5%; BEZ235, 42.5%). Triple therapy with cetuximab provided further advantage (DCR, 88%). The extent of disease control declined at the 6-week evaluation time point (DCRs: AZD6244, 13.9%; BEZ235, 16.2%; AZD6244 + BEZ235, 34%). Cross-analysis of mice harboring xenografts from the same original tumor and treated with each of the different modalities revealed subgroups with preferential sensitivity to AZD6244 (12.5%), BEZ235 (35%), or AZD6244 + BEZ235 (42.5%); another subgroup (10%) showed equivalent response to any treatment.The prevalent growth-suppressive effects produced by MEK and PI3K/mTOR inhibition suggest that this strategy may retard disease progression in patients. However, data offer cautionary evidence against the occurrence of durable responses.
Psychological and Quality-of-Life Outcomes from a Comprehensive Stress Reduction and Lifestyle Program in Patients with Coronary Artery Disease: Results of a Randomized Trial
Authors: Andreas Michalsen, Paul Grossman, Nils Lehmann, Nicola T.M. Knoblauch, Anna Paul, Susanne Moebus, Thomas Budde, Gustav J. Dobos
Journal: Psychotherapy and Psychosomatics (2005)

Stress reduction and comprehensive lifestyle modification programs have improved atherosclerosis and cardiac risk factors in earlier trials. Little is known about the impact of such programs on quality-of-life (QoL) and psychological outcomes. Given recent significant improvements in cardiac care, we evaluated the current benefit of stress reduction/lifestyle modification on QoL and emotional distress in patients with coronary artery disease (CAD).101 patients (59.4 +/- 8.6 years, 23 female) with CAD were randomized to a 1-year lifestyle/stress management program (n = 48) or written advice (n = 53). QoL and psychological outcomes were assessed with the SF-36, Beck Depression, Spielberger State/Trait Anxiety, Spielberger State/Trait Anger and Perceived Stress Inventories. Group repeated-measures analyses of variance were performed for all measures.Adherence to the program was excellent (daily relaxation practice 39 +/- 5 vs. 5 +/- 8 min, respectively; p < 0.001). Both groups improved comparably in most dimensions of QoL, and significantly greater improvements for the lifestyle group were found for physical function and physical sum score (p = 0.046 and p = 0.045). Depression, anxiety, anger and perceived stress were reduced similarly in both groups. However, intervention x gender interaction effects revealed greater benefits among women in the lifestyle intervention vs. advice group for depression and anger (p = 0.025 and p = 0.040), but no effects for men.A comprehensive lifestyle modification and stress management program did not improve psychological outcomes in medically stable CAD patients. The program did appear to confer psychological benefits for women but not men. Further trials should investigate gender-related differences in coronary patient responses to behavioral interventions.
Mucin-Producing Neoplasms of the Pancreas: An Analysis of Distinguishing Clinical and Epidemiologic Characteristics
Authors: Stefano Crippa, Carlos Fernández–del Castillo, Roberto Salvia, Dianne Finkelstein, Claudio Bassi, Ismael Domínguez, Alona Muzikansky, Sarah P. Thayer, Massimo Falconi, Mari Mino–Kenudson, Paola Capelli, Gregory Y. Lauwers, Stefano Partelli, Paolo Pederzoli, Andrew L. Warshaw
Journal: Clinical Gastroenterology and Hepatology (2009)
Brain SPECT Imaging of Amphetamine-Induced Dopamine Release in Euthymic Bipolar Disorder Patients
Authors: Amit Anand, Paul Verhoeff, Nicholas Seneca, Sami S. Zoghbi, John P. Seibyl, Dennis S. Charney, Robert B. Innis
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Increased dopaminergic neurotransmission has been implicated in the pathophysiology of bipolar disorder. However, it remains unclear whether the abnormality is due to increased dopamine release or enhanced postsynaptic receptor sensitivity. In this study, dopamine receptor imaging combined with a pharmacological challenge of amphetamine was used to assess both pre- and postsynaptic aspects of dopamine neurotransmission in euthymic bipolar disorder patients.METHOD: Thirteen patients with bipolar disorder (seven medication free and six receiving mood stabilizer therapy) who had been euthymic for more than 4 weeks and 13 age- and gender-matched healthy comparison subjects were included in the study. Single photon emission computed tomography scans were obtained with the striatal dopamine (D2/D3) receptor radiotracer iodobenzamide ([123I]IBZM) before and after an intravenous amphetamine challenge (0.3 mg/kg). Reduction in striatal [123I]IBZM binding potential from the first scan to the second scan was used as an indirect measure of the amount of dopamine released. Behavioral response to amphetamine was measured with the Brief Psychiatric Rating Scale, Young Mania Rating Scale, and visual analogue scales.RESULTS: Bipolar patients and healthy subjects did not differ in terms of mood state or striatal D2 receptor binding at baseline. Amphetamine challenge led to a significantly greater behavioral response in bipolar patients than in healthy subjects. However, there was no significant difference between the two groups in the amphetamine-induced decrease in striatal [123I]IBZM binding.CONCLUSIONS: In a group of euthymic patients with bipolar disorder, this study did not find evidence for increased striatal dopamine release. Instead, these data are consistent with enhanced postsynaptic dopamine responsivity in patients with bipolar disorder.
Impaired c-Jun Amino Terminal Kinase Activity and T Cell Differentiation in Death Receptor 6–deficient Mice
Authors: Haoran Zhao, Minhong Yan, Hua Wang, Sharon Erickson, Iqbal S. Grewal, Vishva M. Dixit
Journal: The Journal of Experimental Medicine (2001)

During an immune response naive T helper (Th) cells differentiate into two functionally distinct subsets, Th1 and Th2, based on their cytokine secretion profile and immunomodulatory function. c-Jun amino terminal kinase (JNK) regulates Th cell differentiation by activating a transcriptional program required for cytokine production. We have recently identified a TNFR superfamily death domain–containing molecule, death receptor (DR)6, which potently activates JNK. T cells from DR6-deficient mice are substantially impaired in JNK activation. When DR6−/− mice were challenged with protein antigen, their T cells hyperproliferate and display a profound polarization toward a Th2 response whereas Th1 differentiation is not equivalently affected. In addition, DR6−/− T cells showed preference toward Th2 differentiation in vitro. The phenotype seen in the DR6−/− mice is not due to the apoptotic pathway. Therefore, DR6, working through JNK, rather than apoptosis, functions to attenuate the Th2 response. This is the first demonstration of a role in the activation and differentiation of Th cells by DR6 in particular and DRs in general.