tbuckley/cabot-search huggingface dataset:
The Future of Benefit-Cost Analyses of the Clean Air Act
Authors: Alan Krupnick, Richard Morgenstern
Journal: Annual Review of Public Health (2002)

▪ Abstract This review examines the first two studies conducted pursuant to a Congressional mandate that the U.S. Environmental Protection Agency analyze the effects of the Clean Air Act on the “public health, economy, and the environment of the United States.” While these studies indicate that overall, the nation received good value for the resources it invested in improving air quality over the past three decades, we don't know if even higher value could have been obtained by changing or eliminating certain potentially inefficient elements. The review focuses on the critical policy and technical choices made in the analyses, including the selection of the appropriate baseline and the level of disaggregation for the studies. It is proposed that a potential third analysis focus on potential new policies not yet mandated by law or regulation. It is also proposed that the next study fill in key information gaps, expand the benefit categories, and incorporate new research on topics such as mortality and morbidity benefits, cost uncertainties, and others.
Urease induced calcium precipitation by Helicobacter species may initiate gallstone formation
Authors: C Belzer, J G Kusters, E J Kuipers, A H M van Vliet
Journal: Gut (2006)

Helicobacter species can colonise the mammalian gastrointestinal and hepatobiliary tract which usually results in a chronic infection coupled to an inflammatory host response. It is therefore not surprising that colonisation with Helicobacter species is linked with a range of inflammation associated gastrointestinal and hepatobiliary diseases.1 Recently, this range has been expanded, with an association of infection with enterohepatic Helicobacter species and the formation of cholesterol gallstones.2

In their study, Maurer and colleagues2 demonstrated that murine infection with the enterohepatic Helicobacter species H bilis and H hepaticus accelerated the formation of cholesterol gallstones in mice fed a lithogenic diet. Although the gallbladder mucosa in mice with gallstones displayed signs of inflammation, Helicobacter species were not cultured from the inflamed gallbladder or bile. Therefore, Maurer et al hypothesised that the chronic immune stimulation caused by Helicobacter species, rather than a direct bacterial factor, led to the production of nucleating agents, thus indirectly linking …
Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys
Authors: Jan Storek, Thurman Gillespy, Hailing Lu, Ansamma Joseph, Monja A. Dawson, Michael Gough, Julia Morris, Robert C. Hackman, Peter A. Horn, George E. Sale, Robert G. Andrews, David G. Maloney, Hans-Peter Kiem
Journal: Blood (2003)
Role of cyclophilin B in tumorigenesis and cisplatin resistance in hepatocellular carcinoma in humans
Authors: Yeonghwan Kim, Miran Jang, Sangbin Lim, Hyeran Won, Kyung-Sik Yoon, Jae-Hoon Park, Hyo Jong Kim, Byung-Ho Kim, Won-Sang Park, Joohun Ha, Sung-Soo Kim
Journal: Hepatology (2011)

Cyclophilin B (CypB) performs diverse roles in living cells, but its role in hepatocellular carcinoma (HCC) is largely unclear. To reveal its role in HCC, we investigated the induction of CypB under hypoxia and its functions in tumor cells in vitro and in vivo. Here, we demonstrated that hypoxia-inducible factor 1α (HIF-1α) induces CypB under hypoxia. Interestingly, CypB protected tumor cells, even p53-defective HCC cells, against hypoxia- and cisplatin-induced apoptosis. Furthermore, it regulated the effects of HIF-1α, including those in angiogenesis and glucose metabolism, via a positive feedback loop with HIF-1α. The tumorigenic and chemoresistant effects of CypB were confirmed in vivo using a xenograft model. Finally, we showed that CypB is overexpressed in 78% and 91% of the human HCC and colon cancer tissues, respectively, and its overexpression in these cancers reduced patient survival.These results indicate that CypB induced by hypoxia stimulates the survival of HCC via a positive feedback loop with HIF-1α, indicating that CypB is a novel candidate target for developing chemotherapeutic agents against HCC and colon cancer.
Three year joint space narrowing predicts long term incidence of knee surgery in patients with osteoarthritis: an eight year prospective follow up study
Authors: O Bruyere
Journal: Annals of the Rheumatic Diseases (2005)

To assess the clinical relevance of mean and minimum femorotibial joint space narrowing (JSN) for predicting future osteoarthritis related surgery in patients with knee osteoarthritis.126 subjects with primary knee osteoarthritis were followed prospectively for a mean eight years. Minimum and mean joint space width (JSW) were assessed from standard x rays at baseline and after a follow up of three years. The rate of knee osteoarthritis related surgery was recorded for the following five years.After a mean follow up of eight years, 16 patients (12.7%) had received osteoarthritis related joint surgery. The areas under the curves (AUC) resulting from the receiver operating characteristic curve analyses for predicting osteoarthritis surgery were 0.73 (p=0.006) for minimum JSN and 0.55 (p=0.54) for mean JSN. The cut off for minimum JSN maximising sensitivity and specificity for predicting future surgery was a change of 0.7 mm or more in minimum joint space width over a period of three years. However, no meaningful differences were observed for cut off values between 0.5 and 0.8 mm The relative risk (adjusted for age, body mass index, baseline symptoms, and baseline JSW) of experiencing osteoarthritis related surgery during the eight year of follow up was 5.15 (95% confidence interval, 1.70 to 15.60) (p=0.004) in patients with a minimum joint space narrowing of 0.7 mm or more during the first three years of the study.A cut off of 0.5 to 0.8 mm in minimum JSN, measured on standard x rays, reflects a clinically relevant progression in patients with knee osteoarthritis.
Long-term follow-up of the <i>MAINTAIN</i> Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis
Authors: Farah Tamirou, David D'Cruz, Shirish Sangle, Philippe Remy, Carlos Vasconcelos, Christoph Fiehn, Maria del Mar Ayala Guttierez, Inge-Magrethe Gilboe, Maria Tektonidou, Daniel Blockmans, Isabelle Ravelingien, Véronique le Guern, Geneviève Depresseux, Loïc Guillevin, Ricard Cervera, Frédéric A Houssiau
Journal: Annals of the Rheumatic Diseases (2015)

Objective To report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome. Methods In 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up. Results Death (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria &lt;0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker. Conclusions The long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome. Trial registration number NCT00204022.
Molecular cloning and expression of the human interleukin 5 receptor.
Authors: Y Murata, S Takaki, M Migita, Y Kikuchi, A Tominaga, K Takatsu
Journal: The Journal of Experimental Medicine (1992)

Human interleukin 5 (IL-5) plays an important role in proliferation and differentiation of human eosinophils. We report the isolation of cDNA clones from cDNA libraries of human eosinophils by using murine IL-5 receptor alpha chain cDNA as a probe. Analysis of the predicted amino acid sequence indicated that the human IL-5 receptor has approximately 70% amino acid sequence homology with the murine IL-5 receptor and retains features common to the cytokine receptor superfamily. One cDNA clone encodes a glycoprotein of 420 amino acids (Mr 47,670) with an NH2-terminal hydrophobic region (20 amino acids), a glycosylated extracellular domain (324 amino acids), a transmembrane domain (21 amino acids), and a cytoplasmic domain (55 amino acids). Another cDNA encodes only the extracellular domain of this receptor molecule. Other cDNA clones encode molecules having diversified cytoplasmic domains. COS7 cells transfected with the cDNA expressed a approximately 60-kD protein and bound IL-5 with a single class of affinity (Kd = 250-590 pM). The Kd values were similar to that observed in normal human eosinophils. In contrast to the murine 60-kD alpha chain, which binds IL-5 with low affinity (Kd = approximately 10 nM), the human alpha chain homologue can bind IL-5 with much higher affinity by itself. RNA blot analysis of human cells demonstrated two transcripts (approximately 5.3 and 1.4 kb). Both of them were expressed in normal human eosinophils and in erythroleukemic cell line TF-1, which responds to IL-5. The human IL-5 receptor characterized in this paper is essential for signal transduction, because expression of this molecule in murine IL-3-dependent cell line FDC-P1 allowed these cells to proliferate in response to IL-5.
A High Molecular Weight Melanoma-Associated Antigen–Specific Chimeric Antigen Receptor Redirects Lymphocytes to Target Human Melanomas
Authors: William R. Burns, Yangbing Zhao, Timothy L. Frankel, Christian S. Hinrichs, Zhili Zheng, Hui Xu, Steven A. Feldman, Soldano Ferrone, Steven A. Rosenberg, Richard A. Morgan
Journal: Cancer Research (2010)

Abstract Immunotherapy, particularly the adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL), is a very promising therapy for metastatic melanoma. Some patients unable to receive TIL have been successfully treated with autologous peripheral blood lymphocytes (PBL), genetically modified to express human leukocyte antigen (HLA) class I antigen–restricted, melanoma antigen–reactive T-cell receptors; however, substantial numbers of patients remain ineligible due to the lack of expression of the restricting HLA class I allele. We sought to overcome this limitation by designing a non–MHC-restricted, chimeric antigen receptor (CAR) targeting the high molecular weight melanoma-associated antigen (HMW-MAA), which is highly expressed on more than 90% of human melanomas but has a restricted distribution in normal tissues. HMW-MAA–specific CARs containing an antigen recognition domain based on variations of the HMW-MAA–specific monoclonal antibody 225.28S and a T-cell activation domain based on combinations of CD28, 4-1BB, and CD3ζ activation motifs were constructed within a retroviral vector to allow stable gene transfer into cells and their progeny. Following optimization of the HMW-MAA–specific CAR for expression and function in human PBL, these gene-modified T cells secreted cytokines, were cytolytic, and proliferated in response to HMW-MAA–expressing cell lines. Furthermore, the receptor functioned in both CD4+ and CD8+ cells, was non–MHC restricted, and reacted against explanted human melanomas. To evaluate this HMW-MAA–specific CAR in patients with metastatic melanoma, we developed a clinical-grade retroviral packaging line. This may represent a novel means to treat the majority of patients with advanced melanoma, most notably those unable to receive current ACT therapies. Cancer Res; 70(8); 3027–33. ©2010 AACR.
Identification of Novel Small Molecule Inhibitors of Hypoxia-Inducible Factor-1 That Differentially Block Hypoxia-Inducible Factor-1 Activity and Hypoxia-Inducible Factor-1α Induction in Response to Hypoxic Stress and Growth Factors
Authors: Noan-Minh Chau, Paul Rogers, Wynne Aherne, Veronica Carroll, Ian Collins, Edward McDonald, Paul Workman, Margaret Ashcroft
Journal: Cancer Research (2005)

Abstract Hypoxia-inducible factor-1 (HIF-1) is a transcriptional complex that is activated in response to hypoxia and growth factors. HIF-1 plays a central role in tumor progression, invasion, and metastasis. Overexpression of the HIF-1α subunit has been observed in many human cancers and is associated with a poor prognostic outcome with conventional treatments. Targeting HIF-1 using novel small molecule inhibitors is, therefore, an attractive strategy for therapeutic development. We have generated U2OS human osteosarcoma cells stably expressing a luciferase reporter construct under the control of a hypoxia response element (U2OS-HRE-luc). The U2OS-HRE-luc cells were robustly and reproducibly sensitive to hypoxic stress in a HIF-1–dependent manner. We developed an automated U2OS-HRE-luc cell-based assay that was used in a high-throughput screen to identify compounds that inhibited HIF-1 activity induced by treatment with the hypoxia mimetic, deferoxamine mesylate. We performed a pilot screen of the National Cancer Institute Diversity Set of 2,000 compounds. We identified eight hit compounds, six of these were also identified by Rapisarda et al. in an independent hypoxia screen. However, there were two novel hit compounds, NSC-134754 and NSC-643735, that did not significantly inhibit constitutive luciferase activity in U2OS cells (U2OS-luc). We showed that both NSC-134754 and NSC-643735 significantly inhibited HIF-1 activity and HIF-1α protein induced by deferoxamine mesylate. Interestingly, NSC-134754 but not NCS-643735 inhibited HIF-1 activity and HIF-1α protein induced by hypoxia and significantly inhibited Glut-1 expression. Finally, we showed that both NCS-134754 and NCS-643735 inhibited HIF-1α protein induced by insulin-like growth factor-1. Our cell-based assay approach has successfully identified novel compounds that differentially target hypoxia and/or growth factor–mediated induction of HIF-1α.
Increased systemic absorption of inhaled corticosteroids in asthmatics with better lung function
Authors: A Saxena
Journal: Thorax (2007)

▴ Mortimer KJ, Harrison TW, Tang Y, et al . Plasma concentrations of inhaled corticosteroids in relation to airflow obstruction in asthma. Br J Clin Pharmacol2006;62:412–19.

[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4]



This study compared the pharmacokinetic profiles of four different inhaled corticosteroids in 30 subjects with asthma who had an FEV1 ranging 36–138% predicted. Each subject inhaled doses of beclometasone, budesonide, fluticasone and mometasone in random order. Plasma concentrations of the drugs were …

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Ocular complications of ulcerative colitis.
Authors: F A Billson, F T De Dombal, G Watkinson, J C Goligher
Journal: Gut (1967)

EDITORIAL COMMENT This study showed that 17 out of 465 patients, i.e., 3.6 %, had ocular complications.These were always associated with at least one other systemic complication and all the patients had joint symptoms.It seems likely that the greater use of corticosteroids may reduce the incidence of eye complications, especially of uveitis.
A newly developed sling incorporating a shock absorber to minimize the motion effect on SpO2 during the 6-minutes-walk test
Authors: Kenji Miyamoto, Yuya Tanaka, Toshiaki Kurimoto
Journal: European Respiratory Journal (2012)

Recently, the degree of desaturation during 6-minute-walk test (6MWT) is considered to have prognostic value in patients with idiopathic pulmonary fibrosis. In this study, we demonstrate a negative effect of motion on SpO2 during the walking, and present a newly developed device that minimizes the negative effect during the test. Subjects and Methods : Ten healthy volunteers (26±11yrs) performed 6MWT in 4 different manners: 1) usual walking, 2) usual walking while trying to minimize the effect of motion on the finger on which the oximeter-probe was placed, 3) usual walking using a newly developed sling with a shock absorber (75g) wrapped around the finger and the probe, and 4) walking on a treadmill at the same speed as the usual 6MWT while the finger and the probe were in a resting position without movement. SpO2 was measured continuously using a Pulsox 300i (Konica-Minolta).

Results : During the usual walking with/without the finger moving, there was severe desaturation of more than 4% from the baseline. However, when walking with the new device or on the treadmill there was only a small change in the SpO2, which was within the accuracy of the oximeter.

View this table:

Motion effects on SpO2





Conclusions : SpO2 monitoring during 6MWT does not provide reliable data on desaturation. However, using the new device, more reliable data on desaturation are available.
A Large Prospective Study of Meat Consumption and Colorectal Cancer Risk: An Investigation of Potential Mechanisms Underlying this Association
Authors: Amanda J. Cross, Leah M. Ferrucci, Adam Risch, Barry I. Graubard, Mary H. Ward, Yikyung Park, Albert R. Hollenbeck, Arthur Schatzkin, Rashmi Sinha
Journal: Cancer Research (2010)

Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U.S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09-1.42; P(trend) < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01-1.32; P(trend) = 0.017) intakes indicated an elevated risk for colorectal cancer. The potential mechanisms for this relation include heme iron (HR, 1.13; 95% CI, 0.99-1.29; P(trend) = 0.022), nitrate from processed meats (HR, 1.16; 95% CI, 1.02-1.32; P(trend) = 0.001), and heterocyclic amine intake [HR, 1.19; 95% CI, 1.05-1.34; P(trend) < 0.001 for 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and HR, 1.17; 95% CI, 1.05-1.29; P(trend) <0.001 for 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx)]. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations.
Pedometers to enhance physical activity in COPD: a randomised controlled trial
Authors: Laura Mendoza, Paula Horta, José Espinoza, Miguel Aguilera, Nicolás Balmaceda, Ariel Castro, Mauricio Ruiz, Orlando Díaz, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2014)

Physical inactivity is a cardinal feature of chronic obstructive pulmonary disease (COPD), and is associated with increased morbidity and mortality. Pedometers, which have been used in healthy populations, might also increase physical activity in patients with COPD. COPD patients taking part in a 3-month individualised programme to promote an increase in their daily physical activity were randomised to either a standard programme of physical activity encouragement alone, or a pedometer-based programme. Assessments were performed by investigators blinded to treatment allocation. Change in average 1-week daily step count, 6-min walking distance (6MWD), modified Medical Research Council scale, St George’s respiratory questionnaire (SGRQ) and COPD assessment test (CAT) were compared between groups. 102 patients were recruited, of whom 97 completed the programme (pedometer group: n=50; control group: n=47); 60.8% were male with a mean± sd age of 68.7±8.5 years, and forced expiratory volume in 1 s (FEV 1 ) 66.1±19.4% and FEV 1 /forced vital capacity 55.2±9.5%. Both groups had comparable characteristics at baseline. The pedometer group had significantly greater improvements in: physical activity 3080±3254 steps·day −1 versus 138.3±1950 steps·day −1 (p&lt;0.001); SGRQ −8.8±12.2 versus −3.8±10.9 (p=0.01); CAT score −3.5±5.5 versus −0.6±6.6 (p=0.001); and 6MWD 12.4±34.6 versus −0.7±24.4 m (p=0.02) than patients receiving activity encouragement only. A simple physical activity enhancement programme using pedometers can effectively improve physical activity level and quality of life in COPD patients.
Vascular brachytherapy for ostial in-stent restenotic lesions
Authors: Costantino O. Costantini, Alexandra J. Lansky, Roxana Mehran, G.S. Mintz, Kartik Desai, Kazuyuki Shirai, Horia Marginean, Gregg W. Stone, George Dangas, Martin B. Leon
Journal: Journal of the American College of Cardiology (2002)