tbuckley/cabot-search huggingface dataset:
Diagnostic Endoscopic Retrograde Cholangiopancreatography
Authors: M. Ciocirlan, T. Ponchon
Journal: Endoscopy (2004)

The United States National Institutes of Health (NIH) State of the Science Conference Statement, published in 2002 [1], reviewed the current indications and future directions for diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP). In biliary stone disease, magnetic resonance cholangiopancreatography (MRCP) and endoscopic ultrasonography (EUS) have replaced purely diagnostic ERCP. In cases of advanced pancreatic malignancy in which chemoradiotherapy is indicated, ERCP may be one of the modalities for tissue sampling by needle aspiration, brush cytology, or forceps biopsy, alone or in combination with other techniques. ERCP is the best method of diagnosis for ampullary malignancies. It is also useful for diagnosing biliary malignancy in patients with underlying sclerosing cholangitis. Purely diagnostic ERCP has no role in acute or chronic pancreatitis. In recurrent pancreatitis of unknown cause, ERCP with sphincter manometry should be used if MRCP or computed tomography (CT) are negative, or should be used without manometry if pancreas divisum is suspected. Purely diagnostic ERCP has no role in the diagnosis of abdominal pain of possible pancreatic or biliary origin. This NIH statement, which is open to discussion, illustrates the way in which the role of diagnostic ERCP is becoming increasingly limited due to the emergence of noninvasive techniques such as MRCP and EUS.
Implementation of guidelines for management of possible multidrug-resistant pneumonia in intensive care: an observational, multicentre cohort study
Authors: Daniel H Kett, Ennie Cano, Andrew A Quartin, Julie E Mangino, Marcus J Zervos, Paula Peyrani, Cynthia M Cely, Kimbal D Ford, Ernesto G Scerpella, Julio A Ramirez
Journal: The Lancet Infectious Diseases (2011)
A1C Level and Future Risk of Diabetes: A Systematic Review
Authors: Xuanping Zhang, Edward W. Gregg, David F. Williamson, Lawrence E. Barker, William Thomas, Kai McKeever Bullard, Giuseppina Imperatore, Desmond E. Williams, Ann L. Albright
Journal: Diabetes Care (2010)

We examined ranges of A1C useful for identifying persons at high risk for diabetes prior to preventive intervention by conducting a systematic review. From 16 included studies, we found that annualized diabetes incidence ranged from 0.1% at A1C <5.0% to 54.1% at A1C >or=6.1%. Findings from 7 studies that examined incident diabetes across a broad range of A1C categories showed 1) risk of incident diabetes increased steeply with A1C across the range of 5.0 to 6.5%; 2) the A1C range of 6.0 to 6.5% was associated with a highly increased risk of incident diabetes, 25 to 50% incidence over 5 years; 3) the A1C range of 5.5 to 6.0% was associated with a moderately increased relative risk, 9 to 25% incidence over 5 years; and 4) the A1C range of 5.0 to 5.5% was associated with an increased incidence relative to those with A1C <5%, but the absolute incidence of diabetes was less than 9% over 5 years. Our systematic review demonstrated that A1C values between 5.5 and 6.5% were associated with a substantially increased risk for developing diabetes.
Effectiveness of Pharmacist Care for Patients With Reactive Airways Disease
Authors: Morris Weinberger, Michael D. Murray, David G. Marrero, Nancy Brewer, Michael Lykens, Lisa E. Harris, Roopa Seshadri, Helena Caffrey, J. Franklin Roesner, Faye Smith, A. Jeffrey Newell, Joyce C. Collins, Clement J. McDonald, William M. Tierney
Journal: JAMA (2002)

2][3][4][5][6][7][8] Although exacerbations are potentially preventable by appropriate drug therapy, 9,10 patients often have difficulty following prescribed regimens.Pharmacists may be able to enhance patients' compliance and outcomes by engaging in pharmaceutical care activities (eg, monitoring symptoms, providing medication counseling, helping resolve drug-related problems, facilitating communication with physicians). 11,12Pharmaceutical care is promising because: (1) pharmacists have the knowledge and skills to iden-
<i>Aurora-A</i> and <i>p16</i> Polymorphisms Contribute to an Earlier Age at Diagnosis of Pancreatic Cancer in Caucasians
Authors: Jinyun Chen, Donghui Li, Chongjuan Wei, Subrata Sen, Ann M. Killary, Christopher I. Amos, Douglas B. Evans, James L. Abbruzzese, Marsha L. Frazier
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Aurora-A and p16 play a major role in cell cycle checkpoint regulation. Both of them are important in the maintenance of centrosome duplication. Therefore, we hypothesized that polymorphisms in the two genes may interact or work together to influence the finely tuned mechanisms of cell cycle regulation that these proteins regulate. The purpose of this study was to investigate the association of the Aurora-A (T91A), and p16 (C540G and C580T) polymorphisms with age at diagnosis of pancreatic cancer. Experimental Design: We genotyped 148 Caucasian patients with a diagnosis of pancreatic cancer for the Aurora-A and p16 polymorphisms using pyrosequencing. We tested the association between age at diagnosis and the Aurora-A and p16 genotypes by comparing Kaplan-Meier curves, evaluating the homogeneity of the curves using the log-rank test. We used Cox proportional hazard regression analysis to estimate the association between time to diagnosis and genotype, adjusting for gender. Results: Patients with the Aurora-A polymorphic genotypes had a median age at diagnosis with pancreatic cancer that was 2.8 years earlier than those with the wild-type genotype [log-rank, P = 0.015; hazard ratio (HR), 1.55; 95% confidence intervals (95% CI), 1.09-2.20]. There was no significant association between the p16 genotypes and age at diagnosis. However, the Aurora-A and p16 C580T polymorphisms combined had a synergistic effect on age-associated risk for early diagnosis of pancreatic cancer. Compared with patients with wild-type genotypes for both genes, the median age at diagnosis for patients with one or two polymorphic alleles for both genes was 12.6 years earlier (log-rank, P = 0.0002; HR, 3.88; 95% CI, 1.94-7.76). No significant associations between the polymorphisms and the cancer metastatic status or survival after diagnosis were found. Conclusions: Our findings suggest that the Aurora-A polymorphism contributes to a significantly earlier age at diagnosis of pancreatic cancer, and that Aurora-A and p16 C580T polymorphisms synergistically contribute to an earlier age at diagnosis of pancreatic cancer.
Relation between bronchial responsiveness to inhaled leukotriene D4 and markers of leukotriene biosynthesis
Authors: P Gyllfors
Journal: Thorax (2005)

<b>Background:</b> While clinical trials with antileukotrienes have shown overall beneficial effects in asthma, the factors that determine leukotriene dependent asthma are still unclear. A study was undertaken to determine whether or not leukotriene responsiveness in the airways correlates with endogenous leukotriene biosynthesis. <b>Methods:</b> Bronchial responsiveness to leukotriene (LT) D<sub>4</sub> was assessed as PD<sub>20</sub>FEV<sub>1</sub> in 20 subjects with mild asthma and 10 healthy controls, and compared with bronchial responsiveness to methacholine and two global measures of leukotriene production—urinary LTE<sub>4</sub> and ex vivo production of LTB<sub>4</sub> in whole blood. <b>Results:</b> In patients with asthma the bronchoconstrictor activity of LTD<sub>4</sub> was about 1300 times greater than methacholine (geometric mean PD<sub>20</sub> 0.69 nmol <i>v</i> 887 nmol). Those who were most responsive to LTD<sub>4</sub> were relatively less responsive to methacholine (p&lt;0.01). There was, however, no correlation between bronchial responsiveness to LTD<sub>4</sub> and urinary LTE<sub>4</sub> or blood ex vivo LTB<sub>4</sub> levels in asthmatic subjects or healthy controls. Subjects with asthma treated with inhaled corticosteroids produced higher levels of LTB<sub>4</sub> (p&lt;0.05). <b>Conclusions:</b> General measures of leukotriene production cannot predict bronchial responsiveness to LTD<sub>4</sub>. The unique bronchoconstrictive potency of LTD<sub>4</sub> on human airways may relate to the locally regulated expression of the cysteinyl LT<sub>1</sub> receptor.
2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2
Authors: Hao Liu, Chen Chen Jiang, Christopher J Lavis, Amanda Croft, Li Dong, Hsin-Yi Tseng, Fan Yang, Kwang Hong Tay, Peter Hersey, Xu Dong Zhang
Journal: Molecular Cancer (2009)

Past studies have shown that sensitivity of melanoma cells to TRAIL-induced apoptosis is largely correlated with the expression levels of TRAIL death receptors on the cell surface. However, fresh melanoma isolates and melanoma tissue sections express generally low levels of death receptors for TRAIL. The clinical potential of TRAIL in the treatment of melanoma may therefore be limited unless given with agents that increase the cell surface expression of TRAIL death receptors. 2-Deoxy-D-glucose (2-DG) is a synthetic glucose analogue that inhibits glycolysis and glycosylation and blocks cell growth. It has been in clinical evaluation for its potential use as an anticancer agent. In this study, we have examined whether 2-DG and TRAIL interact to enhance their cytotoxicity towards melanoma cells.2-DG did not kill melanoma cells, but enhanced TRAIL-induced apoptosis in cultured melanoma cells and fresh melanoma isolates. This was associated with increased activation of the caspase cascade and mitochondrial apoptotic pathway, and was blocked by inhibition of TRAIL-R2, and to a lesser extent, inhibition of TRAIL-R1. Treatment with 2-DG up-regulated TRAIL death receptors, in particular, TRAIL-R2, on the melanoma cell surface. Up-regulation of TRAIL-R2 was due to increased transcription that was not dependent on the transcription factors, p53 and CHOP. Instead, the IRE1 alpha and ATF6 pathways of the unfolded protein response that were activated by 2-DG appeared to be involved. Moreover, XBP-1, which is known to be transcriptionally regulated by ATF6 and functionally activated by IRE1 alpha, was found to play an important role in 2-DG-mediated transcriptional up-regulation of TRAIL-R2 in melanoma cells.These results indicate that 2-DG sensitizes human melanoma cells to TRAIL-induced apoptosis by up-regulation of TRAIL-2 via the ATF6/IRE1 alpha/XBP-1 axis of the unfolded protein response. They suggest that 2-DG is a promising agent to increase the therapeutic response to TRAIL in melanoma.
Inhibition of sodium metabisulphite induced bronchoconstriction by frusemide in asthma: role of cyclooxygenase products.
Authors: B J O'Connor, P J Barnes, K F Chung
Journal: Thorax (1994)

BACKGROUND--Inhaled frusemide inhibits airway responses to sodium metabisulphite and other indirect bronchial challenges in asthma by undetermined mechanisms which may relate to its ability to stimulate prostaglandin release. Inhalation of sodium metabisulphite provokes indirect bronchoconstriction, possibly by activating sensory nerves. To investigate the role of cyclooxygenase products in the airway actions of frusemide and sodium metabisulphite, the effects of a potent cyclooxygenase inhibitor, flurbiprofen, alone and in combination with frusemide were investigated against airway responsiveness to sodium metabisulphite. METHODS--In a double blind double placebo controlled study, 12 mild asthmatic subjects attended on four occasions to undergo three inhalation challenges with sodium metabisulphite. A baseline challenge was performed one hour before oral intake of flurbiprofen 200 mg or matched placebo, and two hours before inhalation of frusemide 40 mg or matched placebo. A second challenge was performed immediately after inhalation of frusemide (two hours after flurbiprofen) with a further challenge three hours later. The log concentration provoking a 20% fall in FEV1 (log PC20) was used to assess airway responsiveness to sodium metabisulphite. RESULTS--Frusemide caused an immediate 1.9 doubling dose protection and a lesser 0.7 doubling dose protection at three hours. This protection was enhanced by flurbiprofen at both time points to 2.7 (early) and 1.9 (late) doubling doses. In addition, flurbiprofen alone significantly reduced airway responsiveness to sodium metabisulphite by 1.1 doubling doses at both two and five hours. CONCLUSIONS--The generation of bronchoprotective prostaglandins is unlikely to underlie the inhibitory action of frusemide against airway responsiveness to sodium metabisulphite. Endogenous contractile prostaglandins within the airways may be involved in the bronchoconstrictor response to sodium metabisulphite.
Quantitative Classification of Mammographic Densities and Breast Cancer Risk: Results From the Canadian National Breast Screening Study
Authors: N. F. Boyd, J. W. Byng, R. A. Jong, E. K. Fishell, L. E. Little, A. B. Miller, G. A. Lockwood, D. L. Tritchler, M. J. Yaffe
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Quantitative Classification of Mammographic Densities and Breast Cancer Risk: Results From the Canadian National Breast Screening Study Get access N. F. Boyd, N. F. Boyd 1Division of Preventive Oncology, The Ontario Cancer Treatment and Research Foundation, Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Byng, J. W. Byng 3Richmann Research Institute, Sunnybrook Health Sciences CentreToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar R. A. Jong, R. A. Jong 4Department of Radiology, Mount Sinai HospitalToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar E. K. Fishell, E. K. Fishell 5Department of Radiology, Women's College HospitalToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar L. E. Little, L. E. Little 2Division of Epidemiology and Statistics, Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar A. B. Miller, A. B. Miller 6Preventive Medicine and Biostatistics, University of Toronto Search for other works by this author on: Oxford Academic PubMed Google Scholar G. A. Lockwood, G. A. Lockwood 2Division of Epidemiology and Statistics, Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar D. L. Tritchler, D. L. Tritchler 2Division of Epidemiology and Statistics, Ontario Cancer InstituteToronto, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar M. J. Yaffe M. J. Yaffe 3Richmann Research Institute, Sunnybrook Health Sciences CentreToronto Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 9, 3 May 1995, Pages 670–675, https://doi.org/10.1093/jnci/87.9.670 Published: 03 May 1995 Article history Received: 31 May 1994 Revision received: 26 September 1994 Accepted: 23 February 1995 Published: 03 May 1995
Immunocompetent autoreactive B lymphocytes are activated cycling cells in normal mice.
Authors: D Portnoï, A Freitas, D Holmberg, A Bandeira, A Coutinho
Journal: The Journal of Experimental Medicine (1986)

Frequencies of B cell clonal precursors producing antibodies that react with mouse thyroglobulin, mouse erythrocytes, beef hemoglobin, KLH, and sheep erythrocytes were determined by limiting dilution analyses among small, resting lymphocytes, and among large activated cells from normal adult mice. While frequencies of clones reacting with external antigens were equally distributed in large and small B cells, most, if not all, autoreactive B lymphocytes were found in the large cell fraction. Analysis of antithyroglobulin hybridomas isolated from normal mice revealed dissociation constants ranging from 10(-6) to 5-6 X 10(-7). Treatment of normal donors with antimitotic drugs dramatically decreases the frequencies of autoreactive B cells, but not those of B lymphocytes reacting with external antigenic molecules. Taken together, these experiments show that immunocompetent, autoreactive B lymphocytes are activated and cycling cells in the peripheral lymphoid tissues of normal individuals.
Selective C4 deficiency, systemic lupus erythematosus, and Whipple's disease.
Authors: M Ehrenfeld, M B Urowitz, M E Platts
Journal: Annals of the Rheumatic Diseases (1984)

A 45-year-old female with selective deficiency of C4 and systemic lupus erythematosus developed puzzling gastrointestinal and systemic symptoms in the last 6 months of her life. Extensive investigation of the gastrointestinal tract did not yield any diagnosis, and the patient died shortly afterwards. Autopsy revealed evidence of a typical Whipple's disease of the jejunum and lymph nodes. This association has not been previously described. The disease is reviewed with emphasis on its being an opportunistic infection in an immunosuppressed host with a complement deficiency and SLE.
Fuc-Tvii Is Required for T Helper 1 and T Cytotoxic 1 Lymphocyte Selectin Ligand Expression and Recruitment in Inflammation, and Together with Fuc-Tiv Regulates Naive T Cell Trafficking to Lymph Nodes
Authors: Glennda Smithson, Clare E. Rogers, Peter L. Smith, E. Paul Scheidegger, Bronislawa Petryniak, Jay T. Myers, David S. L. Kim, Jonathon W. Homeister, John B. Lowe
Journal: The Journal of Experimental Medicine (2001)

To determine how the α(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the selectin ligands they control may contribute to the adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient in either or both enzymes. We find a substantial CHS deficiency in Fuc-TVII−/− mice, and a complete deficiency in Fuc-TIV−/−/Fuc-TVII−/− mice. These defects are not accounted for by alterations in the number or function of epidermal Langerhans cells required for cutaneous antigen processing and presentation. By contrast, defective CHS in Fuc-TVII−/− mice or Fuc-TIV−/−/Fuc-TVII−/− mice is attributed in part to prominent, or nearly complete deficiencies, respectively, in the complement of naive T lymphocytes available in lymph nodes for antigen-dependent activation, expansion, differentiation, and dissemination. Fuc-TVII deficiency also deletes expression of E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous sites in vivo, and thereby controls an essential component of the efferent phase of the cutaneous immune response. These observations indicate that collaborative contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to lymphocyte recruitment, are requisite components of the primary cellular immune response, and assign an essential role to Fuc-TVII in control of E- and P-selectin ligand expression by Th1 and Tc1 lymphocytes.
Raised Plasma Soluble P-Selectin in Peripheral Arterial Occlusive Disease Enhances Leukocyte Adhesion
Authors: K.J. Woollard, D. Kling, S. Kulkarni, A.M. Dart, S. Jackson, J. Chin-Dusting
Journal: Circulation Research (2005)

Raised levels of soluble P-selectin (sP-selectin) have been reported in the plasma of patients with vascular diseases; however, the functional importance of this ligand remains unclear. In this study we have examined a potential role for plasma sP-selectin in regulating neutrophil adhesion in patients with peripheral arterial occlusive disease (PAOD). Patients with PAOD had significantly higher levels of sP-selectin (mean+/-SD: 73.3+/-13.0 versus 16.7+/-6.4 ng/mL) and enhanced whole blood leukocyte adhesion to platelets under shear. To examine whether the raised sP-selectin levels can directly influence leukocyte adhesion, isolated neutrophils were incubated with plasma from PAOD patients before and after immunodepletion of sP-selectin. Neutrophil adhesion to fibrinogen increased 2-fold following incubation with PAOD plasma, which was abrogated on sP-selectin immunodepletion. We subsequently demonstrated that recombinant sP-selectin dose-dependently (75 to 250 ng/mL) increased leukocyte adhesion to fibrinogen and platelet monolayers. This increase was PSGL-1 and Src kinase-dependent and correlated with an increase in sP-selectin-mediated Mac-1 activation. sP-selectin-stimulated neutrophil adhesion to platelet monolayers was inversely correlated with shear, such that at low shear (50 s(-1)) a 92.7%+/-15.7 increase in adhesion was observed decreasing to 38.5%+/-11.9 at 150 s(-1) and 10.1%+/-7.4 at 300 s(-1). These studies suggest a potentially important role for sP-selectin in modulating neutrophil adhesion in patients with PAOD, particularly at sites of low shear, where it raises the possibility that raised plasma sP-selectin levels may enhance leukocyte recruitment to vascular injury and promote disease progression.
DIFFERENTIAL IMMUNOFLUORESCENCE OF FERTILIZED MOUSE EGGS WITH H-2 AND NON H-2 ANTIBODY
Authors: Joy Palm, Susan Heyner, R. L. Brinster
Journal: The Journal of Experimental Medicine (1971)

Mouse embryos at the two-cell and blastocyst stages, as well as unfertilized eggs, have been studied by indirect immunofluorescence for the expression of H-2 and non-H-2 histocompatibility antigens on surface membranes. Serologically-specific reactivity to non-H-2 antibody (H-3 and H-6) was observed as diffuse, patchy staining over the entire surface of the blastomeres at the two-cell stage. In contrast, no reactivity of two-cell or unfertilized egg embryos of four inbred strains was observed when antisera containing only multispecific H-2 cytolytic antibody were used. Antisera containing H-2 along with non-H-2 antibody of unknown specificity showed varying degrees of reactivity, which could be shown by absorption studies to be due to the non-H-2 content of the serum. The results suggest that the initial expression of histocompatibility genes varies and support the hypothesis that the appearance of these cell components may relate to specific stages of differentiation.
Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma
Authors: Maurizio Zangari, Elias Anaissie, Alison Stopeck, Alyssa Morimoto, Nguyen Tan, Jeffrey Lancet, Maureen Cooper, Alison Hannah, Guillermo Garcia-Manero, Stephan Faderl, Hagop Kantarjian, Julie Cherrington, Maher Albitar, Francis J. Giles
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with multiple myeloma (MM). VEGF, a soluble circulating angiogenic molecule, acts via receptor tyrosine kinases, including VEGF receptor 2. SU5416 is a small molecule VEGF receptor 2 inhibitor. Experimental Design: Adult patients with advanced MM were entered on a multicenter phase II study. Results: Twenty-seven patients (median age 69, range 39–79), median 4 (0–10) lines of prior therapy, 14 with prior thalidomide therapy, received SU5416 at 145 mg/m2 twice weekly i.v. for a median of two 4-week cycles (range 0.2–9). Grade 3/4 toxicities were rarely observed; the most frequent was thrombocytopenia (12%). Mild-to-moderate toxicities included nausea (63%), headache (56%), diarrhea, vomiting (both 37%), and fatigue (33%). There were three thromboembolic episodes and five cases of new onset hypertension. Two (7%) patients did not complete the first 4-week cycle of therapy because of adverse events (pneumonia and headache). There were no objective responses. Four patients had disease stabilization for ≥4 months. A decrease in median VEGF plasma levels was observed in patients with stable disease (n = 7) compared with patients with progressive disease (n = 5). Overall median survival was 42 weeks (range 3–92+). Conclusions: Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM.