tbuckley/cabot-search huggingface dataset:
Marine algal toxins: origins, health effects, and their increased occurrence.
Authors: F M Van Dolah
Journal: Environmental Health Perspectives (2000)

Certain marine algae produce potent toxins that impact human health through the consumption of contaminated shellfish and finfish and through water or aerosol exposure. Over the past three decades, the frequency and global distribution of toxic algal incidents appear to have increased, and human intoxications from novel algal sources have occurred. This increase is of particular concern, since it parallels recent evidence of large-scale ecologic disturbances that coincide with trends in global warming. The extent to which human activities have contributed to their increase therefore comes into question. This review summarizes the origins and health effects of marine algal toxins, as well as changes in their current global distribution, and examines possible causes for the recent increase in their occurrence.
Ulcerative Keratitis in Gastrointestinal Stromal Tumor Patients Treated with Perifosine
Authors: Debraj Shome, Jonathan Trent, Ladan Espandar, Elham Hatef, Dejka M. Araujo, C. Diane Song, Stella K. Kim, Bita Esmaeli
Journal: Ophthalmology (2008)
Phase II Study of Everolimus in Patients with Metastatic Colorectal Adenocarcinoma Previously Treated with Bevacizumab-, Fluoropyrimidine-, Oxaliplatin-, and Irinotecan-Based Regimens
Authors: Kimmie Ng, Josep Tabernero, Jimmy Hwang, Emilio Bajetta, Sunil Sharma, Salvatore A. Del Prete, Edward R. Arrowsmith, David P. Ryan, Michaela Sedova, Jin Jin, Kamel Malek, Charles S. Fuchs
Journal: Clinical Cancer Research (2013)

Dysregulation of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR pathway is seen in 40% to 60% of patients with colorectal cancer. Everolimus, an oral inhibitor of mTOR, showed efficacy in patients with metastatic colorectal cancers in phase I studies.In sequential phase II studies assessing two dosing schedules, patients with metastatic colorectal cancers refractory to bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens received everolimus 70 mg/wk (n = 99) or 10 mg/d (n = 100). Primary endpoints were disease control rate (DCR) and objective response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and duration of response or stable disease (SD). Tumor tissue was collected from all patients for predefined exploratory biomarker analyses.Seventy-one patients were included in the per-protocol set for each cohort. DCRs of 31.0% and 32.4% (all SD) were seen in the weekly and daily schedules, respectively. Median duration of SD was 3.9 months in each cohort. Median PFS and OS were 1.8 and 4.9 months and 1.8 and 5.9 months, respectively, for the weekly and daily schedules. Among patients receiving daily everolimus, those with a KRAS mutation experienced significantly shorter median OS (P = 0.008) and lower DCR (P = 0.035) compared with those with wild-type KRAS in exploratory biomarker analyses.Everolimus 70 mg/wk or 10 mg/d was well tolerated but did not confer meaningful efficacy in heavily pretreated patients with metastatic colorectal cancers. Future studies may consider evaluating everolimus in combination with other agents or in patients with dysregulation of the PI3K/Akt/mTOR pathway.
TCT-744 Quantitative Assessment of Balloon-Expandable Valve Position During Transcatheter Aortic Valve Replacement Using Intraoperative Transesophageal Echocardiography
Authors: Leo Marcoff, Omar K. Khalique, Susheel Kodali, Mathew Williams, Tamim Nazif, Jean-Michel Paradis, Isaac George, Martin Leon, Rebecca Hahn
Journal: Journal of the American College of Cardiology (2013)
Molecular mechanism of emodin action: Transition from laxative ingredient to an antitumor agent
Authors: Gopal Srinivas, Suboj Babykutty, Priya Prasanna Sathiadevan, Priya Srinivas
Journal: Medicinal Research Reviews (2006)

Abstract Anthraquinones represent a large family of compounds having diverse biological properties. Emodin (1,3,8‐trihydroxy‐6‐methylanthraquinone) is a naturally occurring anthraquinone present in the roots and barks of numerous plants, molds, and lichens, and an active ingredient of various Chinese herbs. Earlier studies have documented mutagenic/genotoxic effects of emodin, mainly in bacterial system. Emodin, first assigned to be a specific inhibitor of the protein tyrosine kinase p65 lck , has now a number of cellular targets interacting with it. Its inhibitory effect on mammalian cell cycle modulation in specific oncogene overexpressed cells formed the basis of using this compound as an anticancer agent. Identification of apoptosis as a mechanism of elimination of cells treated with cytotoxic agents initiated new studies deciphering the mechanism of apoptosis induced by emodin. At present, its role in combination chemotherapy with standard drugs to reduce toxicity and to enhance efficacy is pursued vigorously. Its additional inhibitory effects on angiogenic and metastasis regulatory processes make emodin a sensible candidate as a specific blocker of tumor‐associated events. Additionally, because of its quinone structure, emodin may interfere with electron transport process and in altering cellular redox status, which may account for its cytotoxic properties in different systems. However, there is no documentation available which reviews the biological activities of emodin, in particular, its growth inhibitory effects. This review is an attempt to analyze the biological properties of emodin, a molecule offering a broad therapeutic window, which in future may become a member of anticancer armamentarium. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 5, 591–608, 2007
Suppression of Cyclin D1 by Hypoxia-Inducible Factor-1 via Direct Mechanism Inhibits the Proliferation and 5-Fluorouracil–Induced Apoptosis of A549 Cells
Authors: Wen Wen, Jin Ding, Wen Sun, Kun Wu, Beifang Ning, Wenfeng Gong, Guoping He, Shanna Huang, Xinyu Ding, Peipei Yin, Lei Chen, Qiong Liu, Weifen Xie, Hongyang Wang
Journal: Cancer Research (2010)

Hypoxia-inducible factor (HIF) and cyclin D1 are both key mediators of cell growth and proliferation in normal and cancer cells. However, the interrelation between HIF and cyclin D1 remains unclear. In the present study, we observed the inverse correlation between cyclin D1 and HIF-1 in hypoxia condition. Overexpression of the dominant negative mutant of HIF-1alpha (DN-HIF) significantly enhanced cyclin D1 expression upon hypoxia or arsenite exposure, suggesting the negative regulation of cyclin D1 by HIF-1. Furthermore, we found that the impairment of HIF-1 increased cyclin D1 expression in A549 pulmonary cancer cells, which in turn promoted G1-S cell cycle transition and cell proliferation. Cyclin D1 expression was increased in s.c. xenograft of DN-HIF stably transfected A549 cells in nude mice compared with that of control cells. Chromatin immunoprecipitation assay revealed that HIF-1 was able to directly bind to the promoter region of cyclin D1, which indicates that the negative regulation of cyclin D1 by HIF-1 is through a direct mechanism. Inhibition of histone deacetylase (HDAC) by pretreatment of cells with trichostatin A or specific knockdown of HDAC7 by its shRNA antagonized the suppression of cyclin D1 by HIF-1, suggesting that HDAC7 is required for HIF-1-mediated cyclin D1 downregulation. Moreover, we found that 5-fluorouracil-triggered apoptosis of DN-HIF-transfected A549 cells was reduced by sicyclin D1 (cyclin D1-specific interference RNA) introduction, suggesting that clinical observation of HIF-1 overexpression-associated chemoresistance might be, at least partially, due to the negative regulation of cyclin D1.
PROTEIN METABOLISM AND PROTEIN RESERVES DURING ACUTE STERILE INFLAMMATION
Authors: S. C. Madden, W. A. Clay
Journal: The Journal of Experimental Medicine (1945)

Adult dogs were given a proteinless diet plus casein, 80 calories/kilo, 0.4 gm. nitrogen/kilo/day. Sterile controlled inflammation was produced by subcutaneous injection of turpentine. The reaction is characterized by local swelling, induration, and abscess formation, terminated by rupture or incision after 3 to 5 days and by general reactions of malaise, fever, leucocytosis, and increased urinary nitrogen. For 3 to 6 days after turpentine the nitrogen intake was provided in seven experiments by amino acids given parenterally (a solution of the ten essential amino acids (Rose) plus glycine). A normal dog with a normal protein intake showed a negative nitrogen balance after turpentine-urinary nitrogen doubled even as in inflammation during fasting. A protein-depleted dog (low protein reserves produced by very low protein intake) given a normal protein intake after turpentine maintained nitrogen balance-urinary nitrogen rose only slightly. With a high (doubled) protein intake the depleted dog showed strongly positive balance. Normal dogs with high (doubled) protein intakes react to turpentine with doubled urinary nitrogen outputs on individual days and therefore are maintained in approximate nitrogen balance and weight balance. This end may be achieved equally well or better by oral feeding, when such is possible and absorption unimpaired. The increased nitrogen excretion after injury is again shown directly related to the state of body protein reserves. Increased catabolism not inhibition of anabolism best explains the excess urinary nitrogen. Protection during injury of valuable protein reserves appears possible through an adequate intake of protein nitrogen.
Rapidity of rheumatology consultation for people in an early inflammatory arthritis cohort
Authors: D E. Feldman, O Schieir, A J Montcalm, S Bernatsky, M Baron
Journal: Annals of the Rheumatic Diseases (2009)

Patients with rheumatoid arthritis (RA) who have contact with a rheumatologist have better health outcomes than those who do not.1 We found that only 27% of newly suspected cases of RA consulted with a rheumatologist.2 However, this study was based on physician billing data; quality control of diagnostic coding and absence of severity indicators limit the conclusions. We pursued this issue further with patients who had a confirmed diagnosis and were in an early arthritis cohort. We hypothesised that this group would represent a “best case scenario” where the majority would have consulted a rheumatologist within the 3-month recommended window.3 We also explored factors that may be associated with referral, including patient characteristics such as laboratory results (C-reactive protein (CRP), rheumatoid factor),4 5 sociodemographic factors and disease severity,2 6 …
Major Depressive Disorder
Authors: R.H. Belmaker, Galila Agam
Journal: New England Journal of Medicine (2008)

This review of major depressive disorder is a comprehensive account of the genetic, biochemical, and neurophysiological changes that have been implicated in the disorder. No single mechanism can account for all the clinical variations in this condition. The monoamine oxidase theory can explain many of the actions of antidepressants, but genetic factors, stress, and psychosocial factors also play a part in depression.
Setting standards based on patients' views on access and continuity: secondary analysis of data from the general practice assessment survey
Authors: P. Bower
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objectives:</b> To examine patients9 views on access and continuity in general practice to derive quality standards. <b>Design:</b> Secondary analysis of data from general practice research studies and routine quality assessment activities undertaken by practices and primary care trusts. <b>Setting:</b> General practice. <b>Participants:</b> General practice patients. <b>Results:</b> Satisfactory standards of access were next day appointments with general practitioners and a 6–10 minute wait for consultations to begin. A satisfactory level of continuity was seeing the same general practitioner "a lot of the time." Standards varied with the analytic method used and by sociodemographic group. <b>Conclusions:</b> Standards expected by patients in primary care can be derived from linked report-assessment pairs. Patients may have expectations of access that are in excess of government targets. Patients also have high expectations of continuity of care. It is unclear the degree to which such standards are reliable or valid, how conflicts between access and continuity should be resolved, or how these standards relate to other priorities of patients such as high quality interpersonal care. <h3>What is already known on this topic</h3> Standards are increasingly being set for the provision of health services Surveys and consultation exercises before the NHS plan helped set the standard for a maximum waiting time of 48 hours for appointments to see general practitioners The optimal methods by which patients should be involved in setting standards and the utility of such standards are unclear <h3>What this study adds</h3> Satisfactory standards of access were next day appointments, a 6–10 minute wait for consultations to begin, and seeing the same general practitioner a lot of the time Patients may have expectations for access to primary care in excess of current government targets
Preclinical and Clinical Development of the Cyclin-Dependent Kinase Inhibitor Flavopiridol
Authors: Geoffrey I. Shapiro
Journal: Clinical Cancer Research (2004)

Abstract Flavopiridol is the first potent inhibitor of cyclin-dependent kinases (cdks) to reach clinical trial. In the majority of solid tumor cell lines and xenografts, flavopiridol induces cell cycle arrest and tumor growth inhibition. This is reflected in clinical outcomes: across multiple Phase II trials there are subsets of patients with prolonged stable disease, although few responses have been observed. Flavopiridol displays sequence-dependent cytotoxic synergy with chemotherapy agents. These effects are most marked when chemotherapy precedes flavopiridol. In the case of DNA-damaging agents that impose S-phase delay, flavopiridol-mediated cdk inhibition disrupts the phosphorylation of E2F-1, leading to inappropriate persistence of its activity, inducing apoptotic pathways. This mechanism has been exploited in a Phase I trial of sequential gemcitabine and flavopiridol that has produced promising results. Flavopiridol is also synergistic with taxanes. Inhibition of cyclin B-cdk1 by flavopiridol accelerates exit from an abnormal mitosis associated with taxane-induced cell death and reduces the phosphorylation of survivin, preventing its stabilization and the cellular protection it affords after taxane exposure. The sequential combination of docetaxel and flavopiridol has been investigated in a Phase I trial in patients with advanced non-small cell lung cancer, and a randomized Phase II study is under way. Initial schedules of flavopiridol used prolonged continuous infusions that produced nanomolar levels of drug thought to be capable of achieving cdk inhibition based on results in tumor cell lines. Recently, it has been discovered that micromolar concentrations are likely to be more effective, and shorter infusions that achieve a higher Cmax have now been adopted. Loading followed by maintenance infusions are also under development, designed to achieve sustained micromolar drug levels. Clinical trials remain complicated by the absence of pharmacodynamic end points to confirm target inhibition.
Delivery of propellant soluble drug from a metered dose inhaler.
Authors: H L Ashworth, C G Wilson, E E Sims, P K Wotton, J G Hardy
Journal: Thorax (1991)

The deposition of particulate suspensions delivered from a metered dose inhaler has been investigated extensively. The distribution of propellant, delivered from a metered dose inhaler, was studied by radiolabelling it with technetium-99m hexamethylpropyleneamine oxime. Andersen sampler measurements indicated that half of the dose was associated with particles in the size range 0.5-5 microns diameter. The preparation was administered to healthy subjects by inhalation and deposition was monitored with a gamma camera. Each lung image was divided into an inner, mid, and peripheral zone. The effects on deposition of varying the size of the delivery orifice (0.46, 0.61, and 0.76 mm internal diameters) and the effect of attaching a spacer were assessed. Lung deposition was independent of the orifice size within the actuator. Without the spacer the average dose deposited in the lungs was 39%, with 15% penetrating into the peripheral part of the lungs. Attachment of the spacer to the mouth-piece increased the mean lung deposition to 57% and reduced oropharyngeal deposition. The study has shown that propellant soluble drugs can be delivered efficiently to the lungs from a metered dose inhaler.
Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins
Authors: Weijia Kong, Jing Wei, Parveen Abidi, Meihong Lin, Satoru Inaba, Cong Li, Yanling Wang, Zizheng Wang, Shuyi Si, Huaining Pan, Shukui Wang, Jingdan Wu, Yue Wang, Zhuorong Li, Jingwen Liu, Jian-Dong Jiang
Journal: Nature Medicine (2004)
Omalizumab for the treatment of allergic bronchopulmonary aspergillosis (ABPA) in children with cystic fibrosis (CF)
Authors: Silvia Gartner, Sandra Rovira, Inés de Mir, Alba Torrent, Belén Caurín, Gabriela Sacoto, Elisa Canino, Antonio Moreno-Galdó
Journal: European Respiratory Journal (2014)

Introduction: ABPA is a complication in CF (2% to 20%) that produces significant respiratory morbidity. It is characterized by an elevated total serum IgE level and IgE antibodies against Aspergillus fumigates antigens, wheezing, bronchiectasis and decline in pulmonary function. Omalizumab is a humanized monoclonal antibody that prevents IgE binding to receptors on effectors cells. Although omalizumab has shown efficacy in allergic asthma, there are only a few publications on the use of omalizumab for treatment ABPA in CF.  Objective and methods: A retrospective study was conducted to assess the use of omalizumab in children with CF and ABPA who were on chronic steroids experiencing significant side effects.  Results:three male CF patients with ABPA started treatment with omalizumab. The diagnosis of ABPA was made at 12, 5 and 10 years of age. Despite of itraconazol and steroids, the patients experienced ABPA exacerbations within the past 4 years and developed severe corticosteroid-related adverse events: growth retardation, cataracts, diabetes. Omalizumab treatment was started at 14, 9 and 12 years of age respectively. After the treatment all patients had significant clinical improvements of respiratory symptoms and lung function (mean FEV1improved from 68% to 94.5%). All patients were discontinued from chronic systemic steroids. During treatment no clinical adverse effects were observed. Omalizumab could be withdrawn after 12 and 18 months in 2 patients. The other patient is continued on omalizumab after three months.  Conclusion:Our experience shows evidence that omalizumab could be effective and safe to control ABPA in steroid dependent CF patients.
<i>TMPRSS2:ETV4</i> Gene Fusions Define a Third Molecular Subtype of Prostate Cancer
Authors: Scott A. Tomlins, Rohit Mehra, Daniel R. Rhodes, Lisa R. Smith, Diane Roulston, Beth E. Helgeson, Xuhong Cao, John T. Wei, Mark A. Rubin, Rajal B. Shah, Arul M. Chinnaiyan
Journal: Cancer Research (2006)

Abstract Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers. Here, we interrogated the expression of all ETS family members in prostate cancer profiling studies and identified marked overexpression of ETV4 in 2 of 98 cases. In one such case, we confirmed the overexpression of ETV4 using quantitative PCR, and by rapid amplification of cDNA ends, quantitative PCR, and fluorescence in situ hybridization, we show that the TMPRSS2 (21q22) and ETV4 (17q21) loci are fused in this case. This result defines a third molecular subtype of prostate cancer and supports the hypothesis that dysregulation of ETS family members through fusions with TMRPSS2 may be an initiating event in prostate cancer development. (Cancer Res 2006; 66(7): 3396-400)
The Association Between Dietary Flavonoid and Lignan Intakes and Incident Type 2 Diabetes in European Populations
Authors: Raul Zamora-Ros, Nita G. Forouhi, Stephen J. Sharp, Carlos A. González, Brian Buijsse, Marcela Guevara, Yvonne T. van der Schouw, Pilar Amiano, Heiner Boeing, Lea Bredsdorff, Françoise Clavel-Chapelon, Guy Fagherazzi, Edith J. Feskens, Paul W. Franks, Sara Grioni, Verena Katzke, Timothy J. Key, Kay-Tee Khaw, Tilman Kühn, Giovanna Masala, Amalia Mattiello, Esther Molina-Montes, Peter M. Nilsson, Kim Overvad, Florence Perquier, J. Ramón Quirós, Isabelle Romieu, Carlotta Sacerdote, Augustin Scalbert, Matthias Schulze, Nadia Slimani, Annemieke M.W. Spijkerman, Anne Tjonneland, Maria Jose Tormo, Rosario Tumino, Daphne L. van der A, Claudia Langenberg, Elio Riboli, Nicholas J. Wareham
Journal: Diabetes Care (2013)

To study the association between dietary flavonoid and lignan intakes, and the risk of development of type 2 diabetes among European populations.The European Prospective Investigation into Cancer and Nutrition-InterAct case-cohort study included 12,403 incident type 2 diabetes cases and a stratified subcohort of 16,154 participants from among 340,234 participants with 3.99 million person-years of follow-up in eight European countries. At baseline, country-specific validated dietary questionnaires were used. A flavonoid and lignan food composition database was developed from the Phenol-Explorer, the U.K. Food Standards Agency, and the U.S. Department of Agriculture databases. Hazard ratios (HRs) from country-specific Prentice-weighted Cox regression models were pooled using random-effects meta-analysis.In multivariable models, a trend for an inverse association between total flavonoid intake and type 2 diabetes was observed (HR for the highest vs. the lowest quintile, 0.90 [95% CI 0.77-1.04]; P value trend = 0.040), but not with lignans (HR 0.88 [95% CI 0.72-1.07]; P value trend = 0.119). Among flavonoid subclasses, flavonols (HR 0.81 [95% CI 0.69-0.95]; P value trend = 0.020) and flavanols (HR 0.82 [95% CI 0.68-0.99]; P value trend = 0.012), including flavan-3-ol monomers (HR 0.73 [95% CI 0.57-0.93]; P value trend = 0.029), were associated with a significantly reduced hazard of diabetes.Prospective findings in this large European cohort demonstrate inverse associations between flavonoids, particularly flavanols and flavonols, and incident type 2 diabetes. This suggests a potential protective role of eating a diet rich in flavonoids, a dietary pattern based on plant-based foods, in the prevention of type 2 diabetes.
Treatment of Superior Vena Cava Syndrome-Reply
Authors: Marc L. Citron
Journal: JAMA (1984)

In Reply.—  Drs Rosenbloom and Rosenfelt question our contention that chemotherapy might replace radiation therapy as standard treatment for SVC syndrome in patients with non-small-cell lung cancer. They claim a radiation therapy response rate of 80% to 90% and wonder whether chemotherapy can do as well. Unfortunately, the studies that they cite include patients with both small-cell and non-small-cell carcinoma with no breakdown of response rates by tumor histology. 1 In treating SVC syndrome or any other manifestations of tumor growth, the most active cytotoxic therapy should be used. In small-cell lung cancer, for example, radiation therapy was the mainstay of therapy for SVC obstruction until effective combination chemotherapy regimens were discovered. Thereafter, in many institutions, chemotherapy has replaced radiation therapy as the treatment of choice. 2,3 Similar reasoning should be used in the management of SVC syndrome in non-small-cell lung cancer. We were encouraged to test chemotherapy in such