tbuckley/cabot-search huggingface dataset:
Mechanism of Bilirubin Diglucuronide Formation in Intact Rats
Authors: Norbert Blanckaert, John Gollan, Rudi Schmid
Journal: Journal of Clinical Investigation (1980)

Although it is well established that bilirubin monoglucuronide is formed in the liver from bilirubin by a microsomal bilirubin uridine diphosphate (UDP)-glucuronosyltransferase, the subcellular site of conversion of monoglucuronide to diglucuronide and the molecular mechanism involved in diglucuronide synthesis have not been identified. Based on in vitro studies, it has been proposed that two fundamentally different enzyme systems may be involved in diglucuronide synthesis in rat liver: (a) a microsomal UDP-glucuronosyltransferase system requiring UDP-glucuronic acid as sugar donor or (b) a transglucuronidation mechanism that involves transfer of a glucuronosyl residue from one monoglucuronide molecule to another, catalyzed by a liver plasma membrane enzyme. To clarify the mechanism by which bilirubin monoglucuronide is converted in vivo to diglucuronide, three different experimental approaches were used. First, normal rats were injected with either equal amounts of bilirubin-IIIα [14C]monoglucuronide and unlabeled bilirubin-XIIIα monoglucuronide, or bilirubin-XIIIα [14C]monoglucuronide and unlabeled bilirubin-IIIα monoglucuronide. Analysis of radiolabeled diglucuronide excreted in bile showed that [14C]glucuronosyl residues were not transferred between monoglucuronide molecules. Second, in normal rats infused intravenously with dual-labeled [3H]bilirubin [14C]monoglucuronide, no transfer or exchange of the [14C]glucuronosyl group between injected and endogenously produced bilirubin monoglucuronide could be detected in the excreted bilirubin diglucuronide. Third, in homozygous Gunn rats, injected 14C-labeled or unlabeled bilirubin mono- or diglucuronides were excreted in bile unchanged (except that diglucuronide was hydrolyzed to a minor degree). This indicates that Gunn rats, which lack bilirubin UDP-glucuronosyltransferase activity, are unable to convert injected monoglucuronide to diglucuronide. Collectively, these findings establish that a transglucuronidation mechanism is not operational in vivo and support the concept that bilirubin diglucuronide is formed by a microsomal UDP-glucuronosyltransferase system.
DSM-III and the transformation of American psychiatry: a history
Authors: M Wilson
Journal: American Journal of Psychiatry (1993)

The author traces the history of the development of DSM-III within the larger context--intellectual, economic, scientific, and ideological--of the development of American psychiatry since World War II. Data were obtained through a literature review, investigation of archival material from the DSM-III task force and APA, and interviews with key participants. This research indicates that from the end of World War II until the mid-1970s, a broadly conceived biopsychosocial model, informed by psychoanalysis, sociological thinking, and biological knowledge, was the organizing model for American psychiatry. However, the biopsychosocial model did not clearly demarcate the mentally well from the mentally ill, and this failure led to a crisis in the legitimacy of psychiatry by the 1970s. The publication of DSM-III in 1980 represented an answer to this crisis, as the essential focus of psychiatric knowledge shifted from the clinically-based biopsychosocial model to a research-based medical model. The author concludes that while DSM-III, and the return to descriptive psychiatry which it inaugurated, has had positive consequences for the profession, at the same time it represents a significant narrowing of psychiatry's clinical gaze.
Abstract 15087: Long-Term Outcomes of Stents vs. Bypass Surgery in Diabetic and Nondiabetic Patients with Multivessel and/or Left Main Coronary Artery Disease: Data From a Large Three-Observational Cohort Study
Authors: Duk-Woo Park, Yong-Giun Kim, Gyung-Min Park, Ki Won Hwang, Chang Hee kwon, Jeong Yoon Jang, Suk-Won Choi, Hae-Geun Song, Jung-Min Ahn, Won-Jang Kim, Jong-Young Lee, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Circulation (2011)

BACKGROUND Patients with diabetes experience a more aggressive form of atherosclerosis than patients without diabetes. Whether or not the long-term results of coronary stenting and coronary-artery ...
Drug Delivery: Enzyme‐Responsive Cell‐Penetrating Peptide Conjugated Mesoporous Silica Quantum Dot Nanocarriers for Controlled Release of Nucleus‐Targeted Drug Molecules and Real‐Time Intracellular Fluorescence Imaging of Tumor Cells (Adv. Healthcare Mater. 8/2014)
Authors: Jinming Li, Fang Liu, Qing Shao, Yuanzeng Min, Marianne Costa, Edwin K. L. Yeow, Bengang Xing
Journal: Advanced Healthcare Materials (2014)

On page 1230, B. Xing, E. K. L. Yeow, and co-workers present a specific tumor microenvironment-responsive silica quantum dot nano-platform where potent antitumor reagents are loaded onto the surface of enzyme activatable cell penetrating peptide conjugated nanoparticles. This personalized nanomedicine platform can be specifically recognized by enzymes found only over-expressed in the tumor cell environment that can selectively control the localized drug release into the nucleus of targeted tumor cells, eliciting significant tumor cytotoxicity with minimum side effects. This platform also provides real-time imaging of the tumor targeting process and intracellular drug delivery.
Encephalitogenic potential of the myelin basic protein peptide (amino acids 83–99) in multiple sclerosis: Results of a phase II clinical trial with an altered peptide ligand
Authors: Bibiana Bielekova, Bonnie Goodwin, Nancy Richert, Irene Cortese, Takayuki Kondo, Ghazaleh Afshar, Bruno Gran, Joan Eaton, Jack Antel, Joseph A. Frank, Henry F. McFarland, Roland Martin
Journal: Nature Medicine (2000)
Carcinogenicity of Subcutaneously Injected N-Nitrosoheptamethyleneimine in European Hamsters2
Authors: Gerd Reznik, Ulrich Mohr, William Lijinsky
Journal: JNCI Journal of the National Cancer Institute (1978)

Male and female European hamsters (45 of each sex) received sc injections once weekly for life of N-nitrosoheptamethyleneimine (NHMI) at one-fifth the median lethal dose (LD50) (females: 44 mg/kg body wt; males: 66 mg/kg body wt), one-tenth the LD50 (females: 22 mg/kg body wt; males: 33 mg/kg body wt), or one-twentieth the LD50 (females: 11 mg/kg body wt; males: 16.5 mg/kg body wt). Survival times for both males and females were dependent on the dose of NHMI. Pulmonary neoplasms were induced in almost all the treated animals. They were histologically diagnosed as adenocarcinomas, squamous cell carcinomas, and mixed cell carcinomas. In addition, nasal cavity tumors developed in all hamsters of all treatment groups; these were papillomas, squamous cell carcinomas, and a few adenocarcinomas. Only 1 tumor of the larynx and 1 tumor of the trachea were observed. Several papillomas and a few carcinomas were also detected in the forestomach. The results were discussed with reference to previous findings in rats and Syrian golden hamsters.
Telephone counseling improves adherence to colposcopy among lower-income minority women.
Authors: C Lerman, P Hanjani, C Caputo, S Miller, E Delmoor, S Nolte, P Engstrom
Journal: Journal of Clinical Oncology (1992)

PURPOSE A randomized trial was conducted to evaluate the impact of a telephone counseling intervention to improve patient adherence to colposcopic examination for suspected cervical intraepithelial neoplasia (CIN). METHODS Subjects were lower-income, minority women who missed a scheduled initial appointment for colposcopy at an urban medical clinic. Patients were randomly assigned to either a control condition (n = 42) or a telephone counseling condition (n = 48). The 15-minute, structured telephone counseling intervention protocol addressed educational, psychosocial, and practical barriers to colposcopy adherence. RESULTS The most common patient-reported barriers to colposcopy adherence included a lack of understanding of the purpose of colposcopy (50%), worry about or fear of cancer (25%), and forgetting (23%). Telephone counseling was found to be highly effective in addressing these barriers and improving adherence to diagnostic follow-up and treatment. Of patients in the control condition, 43% complied with a rescheduled colposcopy appointment, compared with 67% in the telephone counseling condition. Logistic regression analysis indicated that the effect of telephone counseling was independent of sociodemographic confounder variables (odds ratio = 2.6; P less than .003). Additionally, 74% of patients who received the initial telephone counseling adhered to recommended treatment, compared with 53% of patients in the control condition. CONCLUSION Brief, structured telephone contact may be a cost-effective mechanism for improving adherence to diagnostic follow-up and treatment for a variety of cancer screening tests.
HBx relieves chromatin-mediated transcriptional repression of hepatitis B viral cccDNA involving SETDB1 histone methyltransferase
Authors: Lise Rivière, Laetitia Gerossier, Aurélie Ducroux, Sarah Dion, Qiang Deng, Marie-Louise Michel, Marie-Annick Buendia, Olivier Hantz, Christine Neuveut
Journal: Journal of Hepatology (2015)
Extracellular vesicle–derived protein from Bifidobacterium longum alleviates food allergy through mast cell suppression
Authors: Jung-Hwan Kim, Eun-Ji Jeun, Chun-Pyo Hong, Seong-Hoon Kim, Min Seong Jang, Eun-Jung Lee, Sook Jin Moon, Chang Ho Yun, Sin-Hyeog Im, Seok-Geun Jeong, Beom-Young Park, Kyong-Tai Kim, Ju-Young Seoh, Yoon-Keun Kim, Sung-Jong Oh, Jun-Sang Ham, Bo-Gie Yang, Myoung Ho Jang
Journal: Journal of Allergy and Clinical Immunology (2015)
Drinking on special occasions shows huge increase on people's typical drinking estimates
Authors: S. Mayor
Journal: BMJ (2015)

Asking people about their typical alcohol consumption fails to take account of a major increase in their drinking on holidays and special occasions, and this atypical drinking may add an extra 40% to their total alcohol intake, a survey of adults in England has shown.

Researchers asked a nationally representative sample of 6085 people aged 16 and over about their typical drinking and any changes in consumption on what they termed routine atypical days, such as Friday nights, as well as on special occasions …
Second cancer risk following Hodgkin's disease: a 20-year follow-up study.
Authors: F E van Leeuwen, W J Klokman, A Hagenbeek, R Noyon, A W van den Belt-Dusebout, E H van Kerkhoff, P van Heerde, R Somers
Journal: Journal of Clinical Oncology (1994)

PURPOSE To determine risk factors for the development of second primary cancers during long-term follow-up of patients with Hodgkin's disease (HD). PATIENTS AND METHODS We assessed the risk of second cancers (SCs) in 1939 HD patients, who were admitted to the Netherlands Cancer Institute (NKI; Amsterdam) or the Dr Daniel den Hoed Cancer Center (DDHK; Rotterdam) between 1966 and 1986. For 97% of the cohort, we obtained a medical status up to at least January 1989. The median follow-up duration of the patients was 9.2 years; for 17% of the patients, follow-up was longer than 15 years. For more than 98% of all second tumors, the diagnosis was confirmed through a pathology report. RESULTS In all, 146 patients developed a SC, compared with 41.9 cases expected on the basis of incidence rates in the general population (relative risk [RR], 3.5; 95% confidence interval [CI], 2.9 to 4.1). The mean 20-year actuarial risk of all SCs was 20% (95% CI, 17% to 24%). Significantly increased RRs were observed for leukemia (RR, 34.7; 95% CI, 23.6 to 49.3), non-Hodgkin's lymphoma (NHL) (RR, 20.6; 95% CI, 13.1 to 30.9), lung cancer (RR, 3.7; 95% CI, 2.5 to 5.3), all gastrointestinal cancers combined (RR, 2.0; 95% CI, 1.2 to 3.1), all urogenital cancers combined (RR, 2.4; 95% CI, 1.4 to 3.7), melanoma (RR, 4.9; 95% CI, 1.6 to 11.3), and soft tissue sarcoma (RR, 8.8; 95% CI, 1.8 to 25.8). As compared with the general population, the cohort experienced an excess of 63 cancer cases per 10,000 person-years. Cox-model analysis indicated the following as significant risk factors for developing leukemia: first-year treatment with chemotherapy (CT), follow-up treatment with CT, age at diagnosis of HD greater than 40 years, splenectomy, and advanced stage. Patients treated with CT in the 1980s had a substantially lower risk of leukemia than patients treated in the 1970s (10-year actuarial risks of 2.1% and 6.4%, respectively; P = .07). Significant risk factors for NHL were older age, male sex, and combined modality treatment as compared with either modality alone. Risk of lung cancer was strongly related to radiotherapy (RT), while an additional role of CT could not be demonstrated. After more than 15 years of follow-up, women treated with mantle-field irradiation before age 20 years had a greater than forty-fold increased risk of breast cancer (P &lt; .001). CONCLUSION While the long-term consequences of HD treatment as administered in the 1960s and 1970s are still evolving, it is promising that patients who received the new treatment regimens introduced in the 1980s have a much lower leukemia risk than patients treated in earlier years. Beginning 10 years after initial RT, the follow-up program of women who received mantle-field irradiation before age 30 years should routinely include breast palpation and yearly mammography.
Abstract 746: Evaluation Of The Coronary Flow Between The Left And The Right Coronary Network In Patients With Triple Vessel Disease With Chronically Occluded Right Coronary Artery
Authors: I. Abouliatim, J.P. Verhoye, G. Ruggieri, Agnès Drochon, A. Leguerrier, H. Corbineau
Journal: Circulation (2008)
A Phase II Randomized Study of Subcutaneous Ixekizumab, an Anti–Interleukin‐17 Monoclonal Antibody, in Rheumatoid Arthritis Patients Who Were Naive to Biologic Agents or Had an Inadequate Response to Tumor Necrosis Factor Inhibitors
Authors: Mark C. Genovese, Maria Greenwald, Chul‐Soo Cho, Alberto Berman, Ling Jin, Gregory S. Cameron, Olivier Benichou, Li Xie, Daniel Braun, Pierre‐Yves Berclaz, Subhashis Banerjee
Journal: Arthritis & Rheumatology (2014)

To evaluate ixekizumab, an anti-interleukin-17A (anti-IL-17A) monoclonal antibody, in 2 populations of rheumatoid arthritis (RA) patients: biologics-naive patients and patients with an inadequate response to tumor necrosis factor (TNF) inhibitors.In this phase II, randomized, double-blind study, placebo or ixekizumab was administered subcutaneously to 260 biologics-naive patients and 188 patients with an inadequate response to TNF inhibitors at weeks 0, 1, 2, 4, 6, 8, and 10 with concomitant disease-modifying antirheumatic drugs. The primary objective was to determine the dose-response relationship of ixekizumab as measured by the proportion of biologics-naive patients meeting the American College of Rheumatology 20% improvement criteria (ACR20) at week 12.Using a logistic regression model defined a priori, a statistically significant dose-response relationship as measured by ACR20 response rates at week 12 was detected in biologics-naive patients (P = 0.031). For patients with an inadequate response to TNF inhibitors, ACR20 responses at week 12 were significantly better with ixekizumab than placebo (P < 0.05). Decreases in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP), Clinical Disease Activity Index (CDAI), and CRP level from baseline were observed at week 12 in the ixekizumab groups in both populations (P < 0.05 versus placebo). Onset of action was rapid in some dose groups in both populations, with improvements in the ACR20, DAS28-CRP, CRP levels, and CDAI observed by day 3 (P < 0.05). Adverse events occurred with similar frequencies overall in the ixekizumab and placebo groups. Infections were more frequent with ixekizumab than placebo (biologics-naive 25% versus 19%; inadequate responders to TNF inhibitors 27% versus 25%). No mycobacterial or invasive fungal infections were reported.Ixekizumab improved RA signs and symptoms in RA patients who were either naive to biologics treatment or had an inadequate response to TNF inhibitors. The safety profile was similar to that of other biologic agents, with no unexpected safety concerns.
Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms
Authors: Jonine D Figueroa, Stella Koutros, Joanne S Colt, Manolis Kogevinas, Montserrat Garcia-Closas, Francisco X Real, Melissa C Friesen, Dalsu Baris, Patricia Stewart, Molly Schwenn, Alison Johnson, Margaret R Karagas, Karla R Armenti, Lee E Moore, Alan Schned, Petra Lenz, Ludmila Prokunina-Olsson, A Rouf Banday, Ashley Paquin, Kris Ylaya, Joon-Yong Chung, Stephen M Hewitt, Michael L Nickerson, Adonina Tardón, Consol Serra, Alfredo Carrato, Reina García-Closas, Josep Lloreta, Núria Malats, Joseph F Fraumeni, Stephen J Chanock, Nilanjan Chatterjee, Nathaniel Rothman, Debra T Silverman
Journal: JNCI Journal of the National Cancer Institute (2015)

Few studies have demonstrated gene/environment interactions in cancer research. Using data on high-risk occupations for 2258 case patients and 2410 control patients from two bladder cancer studies, we observed that three of 16 known or candidate bladder cancer susceptibility variants displayed statistically significant and consistent evidence of additive interactions; specifically, the GSTM1 deletion polymorphism (Pinteraction ≤ .001), rs11892031 (UGT1A, Pinteraction = .01), and rs798766 (TMEM129-TACC3-FGFR3, Pinteraction = .03). There was limited evidence for multiplicative interactions. When we examined detailed data on a prevalent occupational exposure associated with increased bladder cancer risk, straight metalworking fluids, we also observed statistically significant additive interaction for rs798766 (TMEM129-TACC3-FGFR3, Pinteraction = .02), with the interaction more apparent in patients with tumors positive for FGFR3 expression. All statistical tests were two-sided. The interaction we observed for rs798766 (TMEM129-TACC3-FGFR3) with specific exposure to straight metalworking fluids illustrates the value of integrating germline genetic variation, environmental exposures, and tumor marker data to provide insight into the mechanisms of bladder carcinogenesis.
A multidisciplinary clinic for children with severe asthma: Clinical outcomes and healthcare utilization
Authors: Karen Kam, Gillian Currie, Alberto Nettel-Aguirre, Mitchell Ian
Journal: European Respiratory Journal (2014)

Background:  Children with problematic severe asthma experience significant burden. A novel multidisciplinary clinic aims to improve lung function and decrease healthcare utilization associated with severe asthma.   Objective:  To examine clinical outcomes and healthcare utilization of children with problematic severe asthma managed in a multidisciplinary clinic rather than a standard asthma clinic.   Methods : A quasi-experimental, retrospective study examined the Intensive Management of Asthma Clinic (IMAC)(n=45) and standard asthma clinic (n=113) at a tertiary care children9s hospital. Data collected from 24 months pre/post time 0 (IMAC enrollment, or met criteria for severe asthma) included: FEV1, and oral steroid courses. The number of clinic visits, emergency department (ED) visits, and hospitalizations were extracted from administrative databases. Linear mixed effects models for repeated measures analyzed changes over time.   Results:  Lung function improved over time for children cared for in both settings (ΔFEV1=3%, p   Conclusion:  A multidisciplinary clinic reduces ED visits, and improves lung function of children with problematic severe asthma. Additional clinic visits for IMAC patients are offset by a subsequent decrease in emergency visits for asthma exacerbations.
NK cells and CD8+ T cells cooperate to improve therapeutic responses in melanoma treated with interleukin-2 (IL-2) and CTLA-4 blockade
Authors: Frederick J Kohlhapp, Joseph R Broucek, Tasha Hughes, Erica J Huelsmann, Jevgenijs Lusciks, Janet P Zayas, Hubert Dolubizno, Vidyaratna A Fleetwood, Alisa Grin, Graham E Hill, Joseph L Poshepny, Arman Nabatiyan, Carl E Ruby, Joshua D Snook, Jai S Rudra, Jason M Schenkel, David Masopust, Andrew Zloza, Howard L Kaufman
Journal: Journal for ImmunoTherapy of Cancer (2015)

Melanoma is one of the few types of cancer with an increasing annual incidence. While a number of immunotherapies for melanoma have been associated with significant clinical benefit, including high-dose IL-2 and cytotoxic T lymphocyte antigen 4 (CTLA-4) blockade, clinical response to either of these single agents has been limited to 11-20% of treated patients. Therefore, in this study, we sought to test the hypothesis that the combination of IL-2 and CTLA-4 blockade could mediate a more profound therapeutic response.Here, B6 mice were challenged with poorly immunogenic B16 melanoma on day 0, and treated with CTLA-4 blocking antibody (100 μg/mouse) on days 3, 6, and 9, and IL-2 (100,000 units) twice daily on days 4-8, or both.A highly significant synergistic effect that delayed tumor growth and prolonged survival was demonstrated with the combination immunotherapy compared to either monotherapy alone. The therapeutic effect of combination immunotherapy was dependent on both CD8+ T and NK cells and co-depletion of these subsets (but not either one alone) abrogated the therapeutic effect. CTLA-4 blockade increased immune cell infiltration (including CD8+ T cells and NK cells) in the tumor and IL-2 reduced the proportion of highly differentiated/exhausted tumor-infiltrating NK cells.These results have implications for the design of clinical trials in patients with metastatic melanoma and provide new insights into how the immune system may be mediating anti-tumor activity with combination IL-2 and CTLA-4 blockade in melanoma.
CR-UK biomarker roadmaps
Authors: Maria Lioumi, David Newell
Journal: Clinical Cancer Research (2010)

Abstract A clear consensus is developing in all organizations involved in cancer research and treatment — academic, commercial and governmental — that the effective management of the cancer problem will require a move towards personalized medicine, based on the use of targeted therapies guided by the results of biomarker studies. Recognizing the importance of biomarkers, Cancer Research UK (CR-UK) undertook a strategic Review in Biomarkers in 2008. A major finding was that there is currently no well defined structure or common terminology for the biomarker development process as, for example, there is for the development of a new drug. Thus despite increasing investment in basic research to identify potential biomarkers and a demonstrable enthusiasm from clinicians for access to new biomarkers, the number of biomarkers that have been delivered into clinical practice is very small. As a result, the priority recommendation arising from the review was that “Working with national and international academic and commercial partners, CR-UK should develop a pathway and roadmap for biomarker and imaging discovery and development research.” CR-UK has developed biomarker roadmaps for risk/predisposition, diagnostic, prognostic and predictive, and pharmacological biomarkers. These roadmaps describe the process from initial biomarker discovery, assay development, initial correlation to clinical outcome and clinical qualification.