tbuckley/cabot-search huggingface dataset:
THE ESTIMATION OF PHENOTHIAZINES USING CHEMICALLY IMPREGNATED PAPER STRIPS
Authors: JACK J. HEYMAN, BARBARA BAYNE, SIDNEY MERLIS
Journal: American Journal of Psychiatry (1960)

The Forrest tests and the test strips give essentially the same results. These methods for testing for phenothiazines excreted in the urine require some caution on the part of the observer. A positive test may be indicative of phenothiazine intake, but also may be due to bile pigments or other excretion products. A negative test may be indicative of no drug intake or low intake. When interpreted with caution, these tests remain valid for estimating phenothiazine intake.
Motion control shoe affects temporal activity of quadriceps in runners
Authors: R T H Cheung, G Y F Ng
Journal: British Journal of Sports Medicine (2008)

Objective: Delay onset of the vastus medialis obliquus (VMO) has often been reported to happen in people with patellofemoral pain (PFP). Previous studies revealed that a motion control shoe could check rearfoot pronation in overpronators. Literature suggested that movements of the lower leg could affect patellar tracking; thus motion control shoe may help prevent PFP by controlling excessive foot movements. This study aimed to compare the vasti muscle activities in people with excessive foot pronation when running with different footwear. Methods: Twenty female subjects with rearfoot pronation &gt;6° were tested by running for 10 km on a treadmill on two separate days. During each test, subjects either wore a motion-control running shoe or a neutral running shoe. EMG activities of their right VMO and vastus lateralis (VL) were recorded. Their EMG onset timing and median frequency (MF) were compared between the two shoe conditions. Results: A more significant delay in VMO onset of the running duty cycle was observed in the neutral shoe condition than in the motion control shoe (p&lt;0.001). In the neutral shoe condition, the delay in VMO increased with running mileage (Pearson correlation = 0.948), whereas no such pattern was observed in the motion control shoe. A significant drop in MF of the quadriceps after the 10 km run in both shoe conditions was observed (p ranged from &lt;0.001 to 0.008), and there was a larger drop in VMO MF when running with the neutral shoe. Conclusions: The findings suggest that the motion control shoe may facilitate a stable temporal activation of VMO during running.
Constitutive Endocytosis and Degradation of the Pre-T Cell Receptor
Authors: Maddalena Panigada, Simona Porcellini, Eliane Barbier, Sonja Hoeflinger, Pierre-André Cazenave, Hua Gu, Hamid Band, Harald von Boehmer, Fabio Grassi
Journal: The Journal of Experimental Medicine (2002)

The pre-T cell receptor (TCR) signals constitutively in the absence of putative ligands on thymic stroma and signal transduction correlates with translocation of the pre-TCR into glycolipid-enriched microdomains (rafts) in the plasma membrane. Here, we show that the pre-TCR is constitutively routed to lysosomes after reaching the cell surface. The cell-autonomous down-regulation of the pre-TCR requires activation of the src-like kinase p56lck, actin polymerization, and dynamin. Constitutive signaling and degradation represents a feature of the pre-TCR because the γδTCR expressed in the same cell line does not exhibit these features. This is also evident by the observation that the protein adaptor/ubiquitin ligase c-Cbl is phosphorylated and selectively translocated into rafts in pre-TCR– but not γδTCR-expressing cells. A role of c-Cbl–mediated ubiquitination in pre-TCR degradation is supported by the reduction of degradation through pharmacological inhibition of the proteasome and through a dominant-negative c-Cbl ubiquitin ligase as well as by increased pre-TCR surface expression on immature thymocytes in c-Cbl–deficient mice. The pre-TCR internalization contributes significantly to the low surface level of the receptor on developing T cells, and may in fact be a requirement for optimal pre-TCR function.
<i>Helicobacter hepaticus</i>–Induced Liver Tumor Promotion Is Associated with Increased Serum Bile Acid and a Persistent Microbial-Induced Immune Response
Authors: Alexis García, Yu Zeng, Sureshkumar Muthupalani, Zhongming Ge, Amanda Potter, Melissa W. Mobley, Chakib Boussahmain, Yan Feng, John S. Wishnok, James G. Fox
Journal: Cancer Research (2011)

Abstract Chronic microbial infection influences cancer progression, but the mechanisms that link them remain unclear. Constitutive androstane receptor (CAR) is a nuclear receptor that regulates enzymes involved in endobiotic and xenobiotic metabolism. CAR activation is a mechanism of xenobiotic tumor promotion; however, the effects of chronic microbial infection on tumor promotion have not been studied in the context of CAR function. Here, we report that CAR limits the effects of chronic infection–associated progression of liver cancer. CAR knockout (KO) and wild-type (WT) male mice were treated with or without the tumor initiator diethylnitrosamine (DEN) at 5 weeks of age and then orally inoculated with Helicobacter hepaticus (Hh) or sterile media at 8 weeks of age. At approximately 50 weeks postinoculation, mice were euthanized for histopathologic, microbiological, molecular, and metabolomic analyses. Hh infection induced comparable hepatitis in WT and KO mice with or without DEN that correlated with significant upregulation of Tnfα and toll receptor Tlr2. Notably, DEN-treated Hh-infected KO mice exhibited increased numbers of liver lobes with dysplasia and neoplasia and increased multiplicity of neoplasia, relative to similarly treated WT mice. Enhanced tumor promotion was associated with decreased hepatic expression of P450 enzymes Cyp2b10 and Cyp3a11, increased expression of Camp, and increased serum concentrations of chenodeoxycholic acid. Together, our findings suggest that liver tumor promotion is enhanced by an impaired metabolic detoxification of endobiotics and a persistent microbial-induced immune response. Cancer Res; 71(7); 2529–40. ©2011 AACR.
Evidence for a mature B cell subpopulation in Peyer's patches of young adult xid mice.
Authors: J H Eldridge, H Kiyono, S M Michalek, J R McGhee
Journal: The Journal of Experimental Medicine (1983)

Peyer's patch (PP) and mesenteric lymph node (MLN) cell cultures from young adult X-linked immunodeficient (xid) CBA/N and (CBA/N X DBA/2) F1 male mice support primary anti-sheep erythrocyte (SRBC) plaque-forming cell (PFC) responses, which suggests that gut-associated lymphoreticular tissue (GALT) contains a normal B lymphocyte subpopulation. Further support for this was provided by the observation that PP cells from xid mice gave responses to both TI-1 and TI-2 antigens that were similar to the responses of PP cell cultures from normal mice. Spleen cell cultures from xid mice were unresponsive to SRBC and TI-2 antigens. Proof that GALT of xid mice contain mature B lymphocytes was provided by the demonstration of PP B cells that bear a low density of surface immunoglobulin M. When these cells were separated by flow cytometry and immunized with trinitrophenyl (TNP)-Ficoll in vitro, good anti-TNP PFC responses were observed. These results suggest that GALT of young adult xid mice contain mature B cells and may represent the origin for the mature B cell responses seen in aged xid mice.
Bosentan therapy for portopulmonary hypertension
Authors: M. M. Hoeper, M. Halank, C. Marx, G. Hoeffken, H. J. Seyfarth, J. Schauer, J. Niedermeyer, J. Winkler
Journal: European Respiratory Journal (2005)

The dual endothelin receptor antagonist bosentan has been approved in several countries for pulmonary arterial hypertension, and patients with portopulmonary hypertension (PPHTN) have not specifically been excluded. However, no data have been published on the efficacy and safety of bosentan in this patient population. Here, the first clinical experiences with bosentan in patients with Child A cirrhosis and severe PPHTN are reported. In total, 11 consecutive patients with cirrhosis and severe PPHTN in New York Heart Association Functional Classes III and IV were treated for &gt;1 yr with bosentan. After 1 yr of treatment with bosentan, all patients showed improved symptoms and exercise capacity. The 6-min walking distance increased from 310±102 m at baseline to 388±81 m at 1 yr. Cardiopulmonary exercise testing disclosed a significant increase in peak oxygen uptake, from 12.6±3.5 to 16.6±2.8 mL·min −1 ·kg −1 . Pulmonary vascular resistance fell from 944±519 to 635±321 dynes·s·L −1 . The medication was well tolerated by all patients, and there was no evidence of drug-related liver injury. In conclusion, bosentan proved to be efficacious and safe in a small number of patients with portopulmonary hypertension.
786 INCREASED LEVELS OF SOLUBLE LIGANDS OF THE ACTIVATING NATURAL KILLER RECEPTOR (NKG2D) ARE INDEPENDENT RISK FACTORS FOR ADVANCED FIBROSIS IN LIVER TRANSPLANT RECIPIENTS
Authors: S. Iacob, V.R. Cicinnati, G. Wu, M. Lindemann, F.M. Heinemann, V. Rebmann, P.A. Horn, G.C. Sotiropoulos, H.H. Schmidt, A. Paul, G. Gerken, S. Beckebaum
Journal: Journal of Hepatology (2012)
Echocardiographic and Clinical Outcomes of MitraClip Therapy in Patients Not Amenable to Surgery
Authors: Volker Rudolph, Malgorzata Knap, Olaf Franzen, Michael Schlüter, Tjark de Vries, Lenard Conradi, Johannes Schirmer, Hendrik Treede, Karl Wegscheider, Angelika Costard-Jäckle, Thomas Meinertz, Hermann Reichenspurner, Stephan Baldus
Journal: Journal of the American College of Cardiology (2011)
Fluid Shear Stress Transcriptionally Induces Lectin-like Oxidized LDL Receptor-1 in Vascular Endothelial Cells
Authors: Takatoshi Murase, Noriaki Kume, Risa Korenaga, Joji Ando, Tatsuya Sawamura, Tomoh Masaki, Toru Kita
Journal: Circulation Research (1998)

Abstract —Fluid shear stress has been shown to modulate various endothelial functions, including gene expression. In this study, we examined the effect of fluid shear stress on the expression of lectin-like oxidized LDL receptor-1 (LOX-1), a novel receptor for atherogenic oxidized LDL in cultured bovine aortic endothelial cells (BAECs). Exposure of BAECs to the physiological range of shear stress (1 to 15 dyne/cm 2 ) upregulated LOX-1 protein and mRNA in a time-dependent fashion. LOX-1 mRNA levels peaked at 4 hours, and LOX-1 protein levels peaked at 8 hours. Inhibition of de novo RNA synthesis by actinomycin D totally abolished shear stress–induced LOX-1 mRNA expression. Furthermore, nuclear runoff assay showed that shear stress directly stimulates transcription of the LOX-1 gene. Chelation of intracellular Ca 2+ with quin 2-AM completely reduced shear stress–induced LOX-1 mRNA expression; furthermore, the treatment of BAECs with ionomycin upregulated LOX-1 mRNA levels in a dose-dependent manner. Taken together, physiological levels of fluid shear stress can regulate LOX-1 expression by a mechanism dependent on intracellular Ca 2+ mobilization. Inducible expression of LOX-1 by fluid mechanics may play a role in localized expression of LOX-1 and atherosclerotic lesion formation in vivo.
Kinetics of 14C-glycocholic acid clearance in normal man and in patients with liver disease.
Authors: I T Gilmore, R P Thompson
Journal: Gut (1978)

The plasma clearance of a tracer dose of 14C-glycocholic acid, and fasting total serum bile acid concentrations were measured in 14 control subjects and in 38 patients with acute and chronic liver disease. In controls plasma clearance was 415 +/- 24 ml min-1 m-2 (mean +/- SEM), equivalent to a 'first-pass' extraction by the liver of 85%. Clearance was not significantly different from controls in patients with acute hepatitis or active chronic hepatitis, nor in anicteric patients with primary biliary or alcoholic cirrhosis. Thus bile acid clearance was impaired only in icteric chronic liver disease. In contrast, serum bile acid concentrations were abnormal in all but seven patients, six of whom had active chronic hepatitis in complete biochemical remission. The pattern of plasma disappearance of injected 14C-glycocholic acid was biexponential in controls and patients with liver disease, and computer analysis of the curves suggested that there was significant distribution of bile acid outside the vascular space. The preservation of bile acid clearance in anicteric chronic liver disease confirms that it is dependent more on liver blood flow than on liver cell function.
Building a Protocol Expressway: The Case of Mayo Clinic Cancer Center
Authors: Terre A. McJoynt, Muhanad A. Hirzallah, Daniel V. Satele, Jason H. Pitzen, Steven R. Alberts, S. Vincent Rajkumar
Journal: Journal of Clinical Oncology (2009)

Inconsistencies and errors resulting from nonstandard processes, together with redundancies, rework, and excess workload, lead to extended time frames for clinical trial protocol development. This results in dissatisfaction among sponsors, investigators, and staff and restricts the availability of novel treatment options for patients.A team of experts from Mayo Clinic formed, including Protocol Development Unit staff and management from the three Mayo Clinic campuses (Florida, Minnesota, and Arizona), a systems and procedures analyst, a quality office analyst, and two physician members to address the identified deficiencies. The current-state process was intensively reviewed, and improvement steps were taken to accelerate the development and approval of cancer-related clinical trials. The primary goal was to decrease the time from receipt of a new protocol through submission to an approving authority, such as the National Cancer Institute or institutional review board.Using the Define, Measure, Analyze, Improve, Control (DMAIC) framework infused with Lean waste-reduction methodologies, areas were identified for improvement, including enhancing first-time quality and processing new studies on a first-in/first-out basis. The project was successful in improving the mean turnaround time for internally authored protocols (P < .001) from 25.00 weeks (n = 41; range, 3.43 to 94.14 weeks) to 10.15 weeks (n = 14; range, 4.00 to 22.14 weeks). The mean turnaround time for externally authored protocols was improved (P < .001) from 20.61 weeks (n = 85; range, 3.29 to 108.57 weeks) to 7.79 weeks (n = 50; range, 2.00 to 20.86 weeks).DMAIC framework combined with Lean methodologies is an effective tool to structure the definition, planning, analysis, and implementation of significant process changes.
Efficacy and Safety of Milrinone in Preventing Low Cardiac Output Syndrome in Infants and Children After Corrective Surgery for Congenital Heart Disease
Authors: Timothy M. Hoffman, Gil Wernovsky, Andrew M. Atz, Thomas J. Kulik, David P. Nelson, Anthony C. Chang, James M. Bailey, Akbar Akbary, John F. Kocsis, Raymond Kaczmarek, Thomas L. Spray, David L. Wessel
Journal: Circulation (2003)

Background— Low cardiac output syndrome (LCOS), affecting up to 25% of neonates and young children after cardiac surgery, contributes to postoperative morbidity and mortality. This study evaluated the efficacy and safety of prophylactic milrinone in pediatric patients at high risk for developing LCOS. Methods and Results— The study was a double-blind, placebo-controlled trial with 3 parallel groups (low dose, 25-μg/kg bolus over 60 minutes followed by a 0.25-μg/kg per min infusion for 35 hours; high dose, 75-μg/kg bolus followed by a 0.75-μg/kg per min infusion for 35 hours; or placebo). The composite end point of death or the development of LCOS was evaluated at 36 hours and up to 30 days after randomization. Among 238 treated patients, 25.9%, 17.5%, and 11.7% in the placebo, low-dose milrinone, and high-dose milrinone groups, respectively, developed LCOS in the first 36 hours after surgery. High-dose milrinone significantly reduced the risk the development of LCOS compared with placebo, with a relative risk reduction of 55% ( P =0.023) in 238 treated patients and 64% ( P =0.007) in 227 patients without major protocol violations. There were 2 deaths, both after infusion of study drug. The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% ( P =0.049). Conclusions— The use of high-dose milrinone after pediatric congenital heart surgery reduces the risk of LCOS.
Protein Expression of Platelet-Derived Growth Factor Receptor Correlates with Malignant Histology and PTEN with Survival in Childhood Gliomas
Authors: Halldora K. Thorarinsdottir, Mariarita Santi, Robert McCarter, Elisabeth J. Rushing, Robert Cornelison, Alessandra Jales, Tobey J. MacDonald
Journal: Clinical Cancer Research (2008)

Abstract Purpose: We previously showed that overexpression of epidermal growth factor receptor (EGFR) is associated with malignant grade in childhood glioma. The objective of this study was to determine whether protein expression of EGFR or platelet-derived growth factor receptor (PDGFR) and their active signaling pathways are related to malignant histology, progression of disease, and worse survival. Experimental Design: Tissue microarrays were prepared from untreated tumors from 85 new glioma patients [22 high-grade gliomas (HGG) and 63 low-grade gliomas (LGG)] diagnosed at this institution from 1989 to 2004. Immunohistochemistry was used to assess total expression of EGFR, PDGFRβ, and PTEN and expression of phosphorylated EGFR, phosphorylated PDGFRα (p-PDGFRα), phosphorylated AKT, phosphorylated mitogen-activated protein kinase, and phosphorylated mammalian target of rapamycin. These results were correlated with clinicopathologic data, including extent of initial tumor resection, evidence of dissemination, tumor grade, proliferation index, and survival, as well as with Affymetrix gene expression profiles previously obtained from a subset of these tumors. Results: High expression of p-PDGFRα, EGFR, PDGFRβ, and phosphorylated EGFR was seen in 85.7%, 80.0%, 78.9%, and 47.4% of HGG and 40.0%, 87.1%, 41.7%, and 30.6% of LGG, respectively. However, high expression of p-PDGFRα and PDGFRβ was the only significant association with malignant histology (P = 0.031 and 0.005, respectively); only the loss of PTEN expression was associated with worse overall survival. None of these targets, either alone or in combination, was significantly associated with progression-free survival in either LGG or HGG. Conclusions: High PDGFR protein expression is significantly associated with malignant histology in pediatric gliomas, but it does not represent an independent prognostic factor. Deficient PTEN expression is associated with worse overall survival in HGG.
Eligibility for intravenous thrombolysis in suspected acute myocardial infarction.
Authors: B W Karlson, J Herlitz, N Edvardsson, H Emanuelsson, M Sjölin, A Hjalmarson
Journal: Circulation (1990)

Based on the registration of all the 7,157 patients admitted during a 21-month period to the emergency ward of a single hospital in an urban area with chest pain or other symptoms suggestive of acute myocardial infarction, we studied eligibility for intravenous thrombolysis in suspected acute myocardial infarction. We have limited the present analysis to those 1,715 patients with a strong suspicion of myocardial infarction, and for these patients, we have calculated the percentages eligible for thrombolysis when various electrocardiographic and delay time criteria are applied, but we have not considered contraindications to thrombolysis. We have also calculated the proportions of all infarctions in this group that would thereby receive the treatment, and the proportions of patients treated that would develop a confirmed infarction. Using the criteria ST elevation on the initial electrocardiogram and arrival in hospital within 6 hours from onset of symptoms, 18% of patients would have been given early intravenous thrombolysis, 37% of confirmed infarctions would have been treated, and 91% of all treated patients would have developed a confirmed infarction; with a delay time criterion of 12 hours, these percentages would have been 20%, 41%, and 91%, respectively; with a criterion of 24 hours, they would have been 22%, 45%, and 90%, respectively. By not considering the initial electrocardiogram and applying only the criterion of delay time, these percentages would have been 70%, 72%, and 45%, respectively, for a delay time of 6 hours; 83%, 84%, and 45%, respectively, for a delay time of 12 hours; and 91%, 92%, and 44%, respectively, for a delay time of 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Alexandra B. Lantermann, Dongshu Chen, Kaitlin McCutcheon, Greg Hoffman, Elizabeth Frias, David Ruddy, Daniel Rakiec, Joshua Korn, Gregory McAllister, Frank Stegmeier, Matthew J. Meyer, Sreenath V. Sharma
Journal: Cancer Research (2015)

Abstract Patients with lung tumors harboring activating mutations in the EGF receptor (EGFR) show good initial treatment responses to the EGFR tyrosine kinase inhibitors (TKI) erlotinib or gefitinib. However, acquired resistance invariably develops. Applying a focused shRNA screening approach to identify genes whose knockdown can prevent and/or overcome acquired resistance to erlotinib in several EGFR-mutant non–small cell lung cancer (NSCLC) cell lines, we identified casein kinase 1 α (CSNK1A1, CK1α). We found that CK1α suppression inhibits the NF-κB prosurvival signaling pathway. Furthermore, downregulation of NF-κB signaling by approaches independent of CK1α knockdown can also attenuate acquired erlotinib resistance, supporting a role for activated NF-κB signaling in conferring acquired drug resistance. Importantly, CK1α suppression prevented erlotinib resistance in an HCC827 xenograft model in vivo. Our findings suggest that patients with EGFR-mutant NSCLC might benefit from a combination of EGFR TKIs and CK1α inhibition to prevent acquired drug resistance and to prolong disease-free survival. Cancer Res; 75(22); 4937–48. ©2015 AACR.
A Multifunctional Chimeric Chaperone Serves as a Novel Immune Modulator Inducing Therapeutic Antitumor Immunity
Authors: Xiaofei Yu, Chunqing Guo, Huanfa Yi, Jie Qian, Paul B. Fisher, John R. Subjeck, Xiang-Yang Wang
Journal: Cancer Research (2013)

Converting the immunosuppressive tumor environment into one that is favorable to the induction of antitumor immunity is indispensable for effective cancer immunotherapy. Here, we strategically incorporate a pathogen (i.e., flagellin)-derived, NF-κB-stimulating "danger" signal into the large stress protein or chaperone Grp170 (HYOU1/ORP150) that was previously shown to facilitate antigen crosspresentation. This engineered chimeric molecule (i.e., Flagrp170) is capable of transporting tumor antigens and concurrently inducing functional activation of dendritic cells (DC). Intratumoral administration of adenoviruses expressing Flagrp170 induces a superior antitumor response against B16 melanoma and its distant lung metastasis compared with unmodified Grp170 and flagellin. The enhanced tumor destruction is accompanied with significantly increased tumor infiltration by CD8(+) cells as well as elevation of IFN-γ and interleukin (IL)-12 levels in the tumor sites. In situ Ad.Flagrp170 therapy provokes systemic activation of CTLs that recognize several antigens naturally expressing in melanoma (e.g., gp100/PMEL and TRP2/DCT). The mechanistic studies using CD11c-DTR transgenic mice and Batf3-deficient mice reveal that CD8α(+) DCs are required for the improved T-cell crosspriming. Antibody neutralization assays show that IL-12 and IFN-γ are essential for the Flagrp170-elicited antitumor response, which also involves CD8(+) T cells and natural killer cells. The therapeutic efficacy of Flagrp170 and its immunostimulating activity are also confirmed in mouse prostate cancer and colon carcinoma. Together, targeting the tumor microenvironment with this chimeric chaperone is highly effective in mobilizing or restoring antitumor immunity, supporting the potential therapeutic use of this novel immunomodulator in the treatment of metastatic diseases.