tbuckley/cabot-search huggingface dataset:
Interdisciplinary Critique of Sipuleucel-T as Immunotherapy in Castration-Resistant Prostate Cancer
Authors: M. L. Huber, L. Haynes, C. Parker, P. Iversen
Journal: JNCI Journal of the National Cancer Institute (2012)

Sipuleucel-T was approved by the US Food and Drug Administration on April 29, 2010, as an immunotherapy for late-stage prostate cancer. To manufacture sipuleucel-T, mononuclear cells harvested from the patient are incubated with a recombinant prostatic acid phosphatase (PAP) antigen and reinfused. The manufacturer proposes that antigen-presenting cells exogenously activated by PAP induce endogenous T-cells to attack PAP-bearing prostate cancer cells. However, the lack of demonstrable tumor responses has prompted calls for scrutiny of the design of the trials in which sipuleucel-T demonstrated a 4-month survival benefit. Previously unpublished data from the sipuleucel-T trials show worse overall survival in older vs younger patients in the placebo groups, which have not been shown previously to be prognostic for survival in castration-resistant prostate cancer patients receiving chemotherapy. Because two-thirds of the cells harvested from placebo patients, but not from the sipuleucel-T arm, were frozen and not reinfused, a detrimental effect of this large repeated cell loss provides a potential alternative explanation for the survival "benefit." Patient safety depends on adequately addressing this alternative explanation for the trial results.
Two Cyp19 (P450 Aromatase) Genes on Duplicated Zebrafish Chromosomes Are Expressed in Ovary or Brain
Authors: Evelyn Feng-Lin Chiang, Yi-Lin Yan, Yann Guiguen, John Postlethwait, Bon-chu Chung
Journal: Molecular Biology and Evolution (2001)

Cytochrome P450 aromatase (Cyp19) is an enzyme catalyzing the synthesis of estrogens, thereby controlling various physiological functions of estrogens. We isolated two cyp19 cDNAs, termed cyp19a and cyp19b, respectively, from zebrafish. These genes are located in linkage groups 18 and 25, respectively. Detailed gene mapping indicated that zebrafish linkage groups 18 and 25 may have arisen from the same ancestral chromosome by a chromosome duplication event. Cyp19a is expressed mainly in the follicular cells lining the vitellogenic oocytes in the ovary during vitellogenesis. Cyp19b is expressed abundantly in the brain, at the hypothalamus and ventral telencephalon, extending to the olfactory bulbs. The expression of duplicated cyp19 genes at two different tissues highlights the evolutionary significance of maintaining two active genes on duplicated zebrafish chromosomes for specific functions in the ovary and the brain.
Tenofovir Disoproxil Fumarate in Nucleoside-Resistant HIV-1 Infection
Authors: Kathleen Squires, Anton L. Pozniak, Gerald Pierone, Corklin R. Steinhart, Daniel Berger, Nicholaos C. Bellos, Stephen L. Becker, Michael Wulfsohn, Michael D. Miller, John J. Toole, Dion F. Coakley, Andrew Cheng
Journal: Annals of Internal Medicine (2003)

Background: Resistance to antiretroviral agents remains a leading cause of treatment failure for patients infected with HIV-1. Objective: To describe the efficacy and safety of tenofovir disoproxil fumarate (tenofovir DF) compared with placebo in patients with detectable viral replication despite current antiretroviral therapy. Design: Randomized, double-blind, placebo-controlled study through 24 weeks. After 24 weeks, all patients received open-label tenofovir DF for the remainder of the 48-week study. Setting: 75 North American, European, and Australian HIV clinics. Patients: 552 HIV-1infected adults who were receiving antiretroviral therapy and had stable HIV-1 RNA levels ranging from 400 to 10 000 copies/mL. Measurements: Change in HIV-1 RNA level (time-weighted average from baseline through week 24); proportion of patients with grade 3 or 4 laboratory abnormalities and adverse events; and genotypic HIV-1 resistance testing in a separate substudy at baseline, week 24, and week 48. Results: A statistically significant decrease in HIV-1 RNA level through week 24 (the primary end point) was observed in the tenofovir DF group versus the placebo group (0.61 log10 copies/mL vs. 0.03 log10 copies/mL, respectively [P < 0.001]; difference, 0.58 log10 copies/mL [95% CI, 0.68 to 0.49 log10 copies/mL]). In a virologic substudy, 94% of 253 patients had plasma isolates expressing reverse transcriptase mutations associated with nucleoside resistance mutations at baseline. Through week 24, the incidence of clinical adverse events was similar between patients receiving placebo and those receiving tenofovir DF (14% vs. 13%). No evidence of tenofovir DFrelated toxicity was seen through week 48. Conclusion: In treatment-experienced patients with suboptimal viral suppression, tenofovir DF significantly reduced HIV-1 RNA level and had a safety profile similar to that of placebo. *For members of the Study 907 Team, see the Appendix.
Very high quantitative tumor HER2 content and outcome in early breast cancer
Authors: H. Joensuu, J. Sperinde, M. Leinonen, W. Huang, J. Weidler, P. Bono, V. Kataja, R. Kokko, T. Turpeenniemi-Hujanen, S. Jyrkkiö, J. Isola, P.-L. Kellokumpu-Lehtinen, A. Paquet, Y. Lie, M. Bates
Journal: Annals of Oncology (2011)
Disruption of PAMP-Induced MAP Kinase Cascade by a Pseudomonas syringae Effector Activates Plant Immunity Mediated by the NB-LRR Protein SUMM2
Authors: Zhibin Zhang, Yaling Wu, Minghui Gao, Jie Zhang, Qing Kong, Yanan Liu, Hongping Ba, Jianmin Zhou, Yuelin Zhang
Journal: Cell Host & Microbe (2012)
Back pain in Britain: comparison of two prevalence surveys at an interval of 10 years
Authors: K T Palmer, K Walsh, H Bendall, C Cooper, D Coggon
Journal: BMJ (2000)

tion for publication bias.Moreover, the odds ratio outcome was used exclusively in this investigation.The appearance of a funnel plot can depend on the outcome measure used, and different results might be obtained in some instances if the risk difference or relative risk scale is used.The sensitivity of assessments of publication bias to the outcome measure used requires further investigation.The idea of adjusting the results of meta-analyses for publication bias and imputing "fictional" studies into a meta-analysis is controversial. 15We certainly would not rely on results of imputed studies in forming a final conclusion, partly because asymmetry in a funnel plot may be due to factors other than publication bias.Any adjustment method should be used primarily as a form of sensitivity analysis, to assess the potential effect of missing studies on the meta-analysis, rather than as a means of adjusting results themselves.If, as our study indicates, missing studies change the conclusions in less than 10% of meta-analyses, publication bias, although widespread, may not be a major practical problem.On the other hand, the fact that almost half the funnel plots examined seemed to exhibit some asymmetry leads us to conclude that routine evaluation for this bias should be an important step in any systematic review.Contributors: AJS had the original idea for the study, extracted the relevant data from the Cochrane Database of Systematic Reviews, and assisted with the interpretation of the results.SJD assisted with the study design, carried out the trim and fill analyses, and assisted with the interpretation of
Association of smoking with dsDNA autoantibody production in systemic lupus erythematosus
Authors: M M Freemer
Journal: Annals of the Rheumatic Diseases (2005)

To determine whether exposure to tobacco smoke is associated with double stranded DNA (dsDNA) seropositivity in patients with systemic lupus erythematosus (SLE).Medical record review was used to confirm the diagnosis of SLE and evaluate dsDNA antibody status. Smoking status at the time of autoantibody testing was assessed by patients' questionnaire responses. Multivariate regression analysis was used to determine whether exposure to tobacco smoke is associated with dsDNA seropositivity, while controlling for sex and age at SLE diagnosis.A significantly higher risk of dsDNA seropositivity in current smokers than never smokers (odds ratio (OR) = 4.0, 95% confidence interval (CI) 1.6 to 10.4) was shown by multivariate analysis. Current smokers were found to be at higher risk for dsDNA seropositivity than former smokers (OR = 3.0, 95% CI 1.3 to 7.1). The association between current smoking and dsDNA seropositivity remained significant after adjustment for sex, age at SLE diagnosis, amount smoked, age when smoking began, and the duration of smoking cessation (for former smokers).The association of smoking with dsDNA seropositivity provides insight into the potential mechanisms underlying autoantibody formation. This information may also serve as a possible point of intervention to prevent disease or target treatment.
Rat bite fever without fever
Authors: P Stehle
Journal: Annals of the Rheumatic Diseases (2003)

Rat bite fever is a rarely reported acute febrile bacterial illness caused by <i>Streptobacillus moniliformis</i> or <i>Spirillum minus</i> following a rat bite. It is classically characterised by abrupt onset of fever with rigors, myalgias, headache, and the appearance of a generalised maculopapular petechial skin rash. Polyarthritis complicates the course of the disease in up to 50% of infected patients, and numerous hurdles can make the diagnosis particularly difficult in the absence of fever or rash, as in the present case. A high degree of awareness is necessary to make the correct diagnosis in such cases. Diagnosis has important prognostic implications as the disease is potentially lethal, but easily treatable.
Design and Activity of a Murine and Humanized Anti-CEACAM6 Single-Chain Variable Fragment in the Treatment of Pancreatic Cancer
Authors: Christopher J. Riley, Kevin P. Engelhardt, Jose W. Saldanha, Wenqing Qi, Laurence S. Cooke, Yingting Zhu, Satya T. Narayan, Kishore Shakalya, Kimiko Della Croce, Ivan G. Georgiev, Raymond B. Nagle, Harinder Garewal, Daniel D. Von Hoff, Daruka Mahadevan
Journal: Cancer Research (2009)

Abstract Pancreatic ductal adenocarcinoma (PDA) is a lethal disease, with surgery being the only curative modality for localized disease, and gemcitabine with or without erlotinib remains the standard of therapy for unresectable or metastatic disease. CEACAM6 is overexpressed in human PDA independent of stage or grade and causes anoikis resistance when dysregulated. Because murine monoclonal antibody 13-1 possesses target-specific cytotoxicity in human PDA cell lines, we designed a humanized anti-CEACAM6 single-chain variable fragment (scFv) based on monoclonal antibody 13-1. PEGylation of the glycine-serine linker was used to enhance plasma half-life. These scFvs bound CEACAM6 with high affinity, exhibited cytotoxic activity, and induced dose-dependent poly(ADP-ribose) polymerase cleavage. Murine PDA xenograft models treated with humanized scFv alone elicited tumor growth inhibition, which was enhanced in combination with gemcitabine. Immunohistochemistry showed significant apoptosis, with inhibition of angiogenesis and proliferation, and preservation of the target. Collectively, our results have important implications for the development of novel antibody-based therapies against CEACAM6 in PDA. [Cancer Res 2009;69(5):1933–40]
Apoptosis Signal-Regulating Kinase 1 Plays a Pivotal Role in Angiotensin II–Induced Cardiac Hypertrophy and Remodeling
Authors: Yasuhiro Izumiya, Shokei Kim, Yasukatsu Izumi, Kaoru Yoshida, Minoru Yoshiyama, Atsushi Matsuzawa, Hidenori Ichijo, Hiroshi Iwao
Journal: Circulation Research (2003)

Multiple lines of evidence establish that angiotensin II (Ang II) induces not only hypertension but also directly contributes to cardiac diseases. Apoptosis signal-regulating kinase 1 (ASK1), one of mitogen-activated protein kinase kinase kinases, plays a key role in stress-induced cellular responses. However, nothing is known about the role of ASK1 in cardiac hypertrophy and remodeling in vivo. In this study, by using mice deficient in ASK1 (ASK1 −/− mice), we investigated the role of ASK1 in cardiac hypertrophy and remodeling induced by Ang II. Left ventricular (LV) ASK1 was activated by Ang II infusion in wild-type mice, which was mediated by angiotensin II type 1 receptor and superoxide. Although Ang II-induced hypertensive effect was comparable to wild-type and ASK1 −/− mice, LV ASK1 activation by Ang II was not detectable in ASK1 −/− mice, and p38 and c-Jun N-terminal kinase (JNK) activation was lesser in ASK −/− mice than in wild-type mice. Elevation of blood pressure by continuous Ang II infusion was comparable between ASK1 −/− and wild-type mice. However, Ang II–induced cardiac hypertrophy and remodeling, including cardiomyocyte hypertrophy, cardiac hypertrophy–related mRNA upregulation, cardiomyocyte apoptosis, interstitial fibrosis, coronary arterial remodeling, and collagen gene upregulation, was significantly attenuated in ASK1 −/− mice compared with wild-type mice. These results provided the first in vivo evidence that ASK1 is the critical signaling molecule for Ang II–induced cardiac hypertrophy and remodeling. Thus, ASK1 is proposed to be a potential therapeutic target for cardiac diseases.
Oral nicorandil may induce skin ulcerations
Authors: Su‐Yun Li, Wen‐Qing Li
Journal: British Journal of Dermatology (2015)

Journal Article Oral nicorandil may induce skin ulcerations Get access Su‐Yun Li, Su‐Yun Li Department of Epidemiology School of Public Health Shandong University Jinan Shandong Province People's Republic of ChinaDepartment of Dermatology Warren Alpert Medical School Brown University Providence RI U.S.A Search for other works by this author on: Oxford Academic Google Scholar Wen‐Qing Li Wen‐Qing Li Department of Dermatology Warren Alpert Medical School Brown University Providence RI U.S.ADepartment of Epidemiology School of Public Health Brown University Providence RI U.S.A Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 2, 1 August 2015, Pages 328–329, https://doi.org/10.1111/bjd.13936 Published: 01 August 2015
IL-13/CD14 Polymorphisms and Prenatal Risk Factors That Shape Gut Microbiota Influence the Development of Atopic Dermatitis in Infancy in a Synergistic Manner: A Birth Cohort Study (COCOA)
Authors: So Yeon Lee, Hae-Ran Lee, Kang Mo Ahn, Kyung Won Kim, Youn Ho Shin, Gyeong-shin Lee, Seo Ah Hong, Young-Ho Ho Jung, Eun Lee, Song-Yi Yang, Ju-Hee Seo, Ji-Won Kwon, Byoung-Ju Kim, Byoung-Ju Kim, Hyo-Bin Kim, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2014)

Although cesarean delivery and prenatal exposure to antibiotics are likely to affect the gut microbiome in infancy, their effect on the development of atopic dermatitis (AD) in infancy is unclear. The influence of individual genotypes on these relationships is also unclear. To evaluate with a prospective birth cohort study whether cesarean section, prenatal exposure to antibiotics, and susceptible genotypes act synergistically to promote the development of AD in infancy. The study population comprised 412 infants from the Cohort for Childhood of Asthma and Allergic Diseases (COCOA). Their cord blood DNA was subjected to IL13 (rs20541) and CD14 (rs2569190) genotype analysis. Fecal samples were obtained from 11 of the 412 infants in this study at the age of 6 months and 16s rRNA bacterial gene sequencing was performed. The combination of cesarean delivery and prenatal exposure to antibiotics associated significantly and positively with AD (aOR, 5.70; 95% CI, 1.19–27.3). The association between cesarean delivery and AD was significantly modified by parental history of allergic diseases or risk-associated IL-13 (rs20541) and CD14 (rs2569190) genotypes. Infants who were exposed prenatally to antibiotics and were born by cesarean delivery had lower total microbiota diversity in stool samples at 6 months of age than the control group. As the number of these risk factors increased, the AD risk rose (trend p<0.05). Cesarean delivery and prenatal antibiotic exposure may affect the gut microbiota, which may in turn influence the risk of AD in infants. These relationships may be shaped by the genetic susceptibility alleles.
Interventional approaches to deep vein thrombosis
Authors: Suresh Vedantham
Journal: American Journal of Hematology (2012)

Abstract The last decade has seen increased use of aggressive, catheter‐based methods of treating deep vein thrombosis (DVT). In this article, we outline the risks, benefits, and uncertainties surrounding endovascular DVT therapies, describe clinical situations in which endovascular treatment options should reasonably be considered, and update the reader on new outcome data that pertains to catheter‐based DVT interventions. Endovascular thrombolytic therapy is reasonable to perform for selected patients with DVT causing acute limb‐threatening circulatory compromise, acute inferior vena cava occlusion, or acute iliofemoral DVT for the purposes of limb salvage and relief of presenting DVT symptoms, and appears likely to prevent post‐thrombotic syndrome (PTS) in patients with proximal DVT. A multicenter randomized trial, the ATTRACT Study, is currently underway in the United States to determine whether pharmacomechanical catheter‐directed thrombolysis (PCDT) is sufficiently safe and effective to be recommended for routine use in proximal DVT patients. Selected patients with established moderate‐to‐severe PTS in association with an occluded iliac vein or a refluxing saphenous vein may also be amenable to endovascular intervention to reduce venous hypertension, alleviate symptoms, and improve limb function and quality of life. Pending the results of further studies, an individualized approach to patient selection for interventional DVT therapies is recommended. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.
The Stromal Derived Factor–1/CXCL12–CXC Chemokine Receptor 4 Biological Axis in Non–Small Cell Lung Cancer Metastases
Authors: Roderick J. Phillips, Marie D. Burdick, Marin Lutz, John A. Belperio, Michael P. Keane, Robert M. Strieter
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Non-small cell lung cancer is characterized by a specific metastatic pattern. The mechanism for organ-specific metastasis is poorly understood, although evidence has suggested that the chemokine stromal derived factor-1 (CXCL12) and its cognate receptor CXCR4 may regulate breast cancer metastasis. We hypothesized that the CXCL12-CXCR4 biological axis is important in mediating non-small cell lung cancer metastases. Our results indicate that both non-small cell lung cancer tumor specimens resected from patients and non-small cell lung cancer cell lines express CXCR4, but not CXCL12. Non-small cell lung cancer cell lines undergo chemotaxis in response to CXCL12. CXCL12-CXCR4 activation of non-small cell lung cancer cell lines showed intracellular calcium mobilization and mitogen-activated protein kinase activation with enhanced extracellular signal-related kinase-1/2 phosphorylation without change in either proliferation or apoptosis. Target organs in a murine model that are the preferred destination of human non-small cell lung cancer metastases elaborate higher levels of CXCL12 than does the primary tumor, and suggest the generation of chemotactic gradients. The administration of specific neutralizing anti-CXCL12 antibodies to severe combined immunodeficient mice expressing human non-small cell lung cancer abrogated organ metastases, without affecting primary tumor-derived angiogenesis. These data suggest that the CXCL12-CXCR4 biological axis is involved in regulating the metastasis of non-small cell lung cancer.
Acute Left Ventricular Dynamic Effects of Primary Percutaneous Coronary Intervention
Authors: Maurice Remmelink, Krischan D. Sjauw, José P.S. Henriques, Marije M. Vis, René J. van der Schaaf, Karel T. Koch, Jan G.P. Tijssen, Robbert J. de Winter, Jan J. Piek, Jan Baan
Journal: Journal of the American College of Cardiology (2009)
Atypical familial dysbetalipoproteinemia associated with apolipoprotein phenotype E3/3.
Authors: R J Havel, L Kotite, J P Kane, P Tun, T Bersot
Journal: Journal of Clinical Investigation (1983)

Familial dysbetalipoproteinemia has been reported to be associated uniquely with an apolipoprotein E phenotype (E2/2) that occurs in approximately 1% of all persons. We have observed the typical clinical and biochemical characteristics of this disorder in five members of a family, in all of whom the apolipoprotein E phenotype, as determined by isoelectric focusing electrophoresis, is E3/3. The disorder is present in three generations of the family: the proband, her mother, and three of the proband's five children. The proband's husband, father of all five children, also has apolipoprotein E phenotype E3/3, as do his two unaffected children. As in normal persons with phenotype E3/3, the apolipoprotein E of affected members appears to have a single residue of cysteine. When incorporated with egg lecithin into discoidal complexes, the apolipoprotein E from affected members was taken up normally into perfused livers of estradiol-treated rats, in which a high level of LDL receptors is expressed. When isoelectric focusing electrophoresis was carried out over a narrow range of pH (5-7), each of the apolipoprotein E isoforms of affected members was observed as a doublet, even after reduction of dimers of the protein with 2-mercaptoethanol and treatment with neuraminidase to minimize the content of sialylated forms of the protein. Doublets were also observed in the apolipoprotein E-2 of patients with classical dysbetalipoproteinemia, but only in the affected members of the family with atypical dysbetalipoproteinemia were the components of the doublets equally prominent. As in classical dysbetalipoproteinemia, both apolipoprotein B-100 and B-48 were present in the very low density lipoprotein fraction of plasma obtained in the postabsorptive state, indicating that remnantlike lipoproteins of both hepatic and intestinal origin accumulate. This observation, together with available evidence on the structural and functional heterogeneity of human apolipoprotein E, lead us to suggest that the disorder in this family is caused by one or two structurally abnormal forms of apolipoprotein E that contain a single residue of cysteine.
Demographics and environmental factors in a Wegener's granulomatosis cluster
Authors: J H M Lee, T Attygalle, K Gaffney, D G I Scott
Journal: Annals of the Rheumatic Diseases (2006)

Wegener’s granulomatosis is a multiorgan systemic disease of unknown aetiology, characterised by granulomatous inflammation and vasculitis in small or medium-sized blood vessels. Available evidence suggests a role for genetics, microbial pathogens and environmental exposures in its aetiology.1 Agents including silica,2 hydrocarbons,3 pesticides,4 fumes4 and farming5 have been implicated. We describe the demographic details and environmental exposures of a cluster of patients with Wegener’s granulomatosis cases diagnosed in Norfolk, UK. Cluster analysis enables identification of common environmental exposures that may be temporally and spatially related to disease features.

We identified eight patients who were diagnosed with Wegener’s granulomatosis between February 2005 and February 2006. All patients fulfilled the …