tbuckley/cabot-search huggingface dataset:
Pleural eicosanoids in patients with lung cancer
Authors: Jae Hwa Cho, Sunghyouk Park, Haesung Nam, Seungmin Kwak, Jeongseon Ryu, Honglyeol Lee
Journal: European Respiratory Journal (2013)

Introduction: Malignant pleural effusion can be diagnosed by cytology and biopsy. The accuracy of pleural cytology was 96.5%, but diagnostic discrepancies were 3.5%. The prostaglandins and leukotrienes involved in cancer progression. We investigated the possibility of biomarkers of malignant pleural effusion using NMR-based metabolomics approach.

Materials and methods: We prospectively collected pleural effusion fluids from patients with lung cancer and benign lung diseases (tuberculosis and pneumonia) at Inha University Hospital (Incheon, Republic of Korea) between January 2012 and September 2012. Liquid chromatography-tandem mass spectrometry was used for analysis. We detected DHA, AA, 20-carboxy-LTB4, 6-keto-PGE1a, 20-hydroxy LTB4, PGE2, TXB2, LXA4, LTE4, PGA1, 20-HRTR, 11-dehydro-TXB2.

Results: Eleven patients with lung cancer and twelve with benign were analyzed. The 20-hydroxy LTB4, LXA4, DHA, AA in pleural fluid were increased in cancer group (p<0.05, respectively).

Conclusion: Some of eicosanoids such as AA, 20-carboxy LTB4 might be a role in cancer progression. Further large scaled study will be needed to confirm this findings.
Hemostatic Factors and the Risk of Myocardial Infarction or Sudden Death in Patients with Angina Pectoris
Authors: Simon G. Thompson, Joachim Kienast, Stephen D.M. Pyke, Frits Haverkate, Jürgen C.W. van de Loo
Journal: New England Journal of Medicine (1995)

Increased levels of certain hemostatic factors may play a part in the development of acute coronary syndromes and may be associated with an increased risk of coronary events in patients with angina pectoris.
Abstract 21316: Improved Renal Function With Continuous Flow Left Ventricular Assist Support is Associated With Aortic Valve Opening at 3 Months
Authors: John A Schirger, Yan Topilsky, Brooks S Edwards, Sudhir Kushwaha, Barry Boilson, Richard Daly, Lyle Joyce, John C Burnett, Horng H Chen, Lucian Durham, Soon J Park
Journal: Circulation (2010)
Low plasma CC16 levels in smokers are associated with a higher risk for chronic bronchitis
Authors: Hans Petersen, Shuguang Leng, Steven A. Belinsky, Bruce E. Miller, Ruth Tal-Singer, Caroline A. Owen, Bartolome Celli, Yohannes Tesfaigzi
Journal: European Respiratory Journal (2015)

Club cell protein (CC16 in humans) plays a crucial role in maintaining homeostasis of the airway epithelium [1] and has anti-inflammatory activity in the lung [2]. Serum CC16 levels are low in cigarette smokers [3] and increase following smoking cessation [4], but patients with chronic obstructive pulmonary disease (COPD) show progressive decrease in CC16 with disease severity [5]. Thus, although the association between circulating levels of CC16 and airflow obstruction is accepted, the association between circulating CC16 and chronic bronchitis, and whether a link in association exists between circulating CC16 levels, lung function decline and chronic bronchitis have not been shown. Therefore, we tested the hypothesis that circulating levels of CC16 are associated with the presence of chronic bronchitis in ever smokers. Plasma CC16 levels are associated with CC16 gene polymorphisms and inversely with chronic bronchitis <http://ow.ly/O8CHk>
Graphic representation of the life course of illness in patients with affective disorder
Authors: R M Post, P P Roy-Byrne, T W Uhde
Journal: American Journal of Psychiatry (1988)

The authors illustrate methods for the graphic depiction of the course of unipolar and bipolar affective illness. The utility and advantages of such an approach include 1) accurate assessment of episode patterns, 2) elucidation of relationships to environmental events, endocrine and seasonal factors, and psychosocial stressors, 3) better delineation of treatment response, 4) a greater understanding of the longitudinal and characteristic patterns of illness, and 5) the associated better patient management with psychotherapeutic and pharmacological interventions.
Sulfasalazine: Potential use of an old drug for treatment of pancreatic cancer
Authors: Maisie Lo, Dan Doxsee, Yuwei Wang, Hui Xue, Victor Ling, Yu-Zhuo Wang, Peter W. Gout
Journal: Cancer Research (2006)

4705  Pancreatic cancer is one of the most aggressive and therapy-resistant cancers known. Although chemotherapy using gemcitabine has yielded increases in patient survival, there is no effective therapy for this disease. We have previously found that sulfasalazine (SASP), an established anti-inflammatory drug, can arrest proliferation of lymphoma and prostate cancer cells both in vitro at patient-tolerated levels (∼0.2 mM) and in experimental animals. The in vitro action of SASP is largely based on inhibition of cystine uptake via the xc- cystine/glutamate antiporter. This amino acid, essential for cell growth and viability, cannot be synthesized by certain cancers, rendering them dependent on its uptake from their environment. In the present study we investigated the potential usefulness of SASP for therapy of pancreatic cancer. Human pancreatic cancer cell lines, Mia PaCa-2, Panc-1 and Bxpc-3, were incubated with SASP at a range of concentrations for various periods and cell numbers determined via the WST-1 cell proliferation assay. RT-PCR was used to determine mRNA expression of the xCT subunit of the xc- cystine transporter. In vivo activity of SASP was evaluated using Rag-2M mice carrying subrenal capsule xenografts of the cancer cells (about 80 mm3). I.p. injections of saline or SASP (250 mg/kg body weight) were administered every 12 h for 7 days; the effect of gemcitabine (120 mg/kg body weight; i.p.), twice a week for 7 days, was also assessed. Animals were then sacrificed and tumors harvested for volume measurement and histological analysis. In vitro, Mia PaCa-2 and Panc-1 cells were particularly sensitive to growth inhibition and lytic action by SASP (IC50 = 0.05 mM and 0.1 mM, respectively); the inhibition could be prevented by 60 μM 2-mercaptoethanol allowing cystine uptake via the leucine transporter. The Bxpc-3 cells were less sensitive to SASP (IC50 = 0.35 mM), showing increased expression of xc-, as indicated by elevated xCT-mRNA levels. In vivo, both SASP and gemcitabine inhibited growth of xenografts of the three cell lines, showing growth arrest of about 40-60% (relative to controls), without major toxicity to the hosts. While the growth-inhibitory effect of SASP on pancreatic cancer cell proliferation in vitro involves cystine starvation, the anticancer activity of SASP in vivo needs further investigation. Nevertheless, the marked anti-tumor activity of SASP without major toxicity to the hosts suggests that this established drug could be useful in combination chemotherapy of pancreatic cancer. Supported by the Canadian Institutes of Health Research (PWG/YZW).
Dexamethasone-Induced Thymocyte Apoptosis: Apoptotic Signal Involves the Sequential Activation of Phosphoinositide-Specific Phospholipase C, Acidic Sphingomyelinase, and Caspases
Authors: Maria Grazia Cifone, Graziella Migliorati, Raffaella Parroni, Cristina Marchetti, Danilo Millimaggi, Angela Santoni, Carlo Riccardi
Journal: Blood (1999)
Cetuximab for Metastatic Colorectal Cancer
Authors: Fausto Roila, Marina Chiara Garassino, Enzo Ballatori
Journal: New England Journal of Medicine (2009)

To the Editor: As a gastroenterologist who claims to have been the first physician in Connecticut to give fluorouracil to a patient with colon cancer, I was delighted to read in the Conclusions of the Abstract of the article by Van Cutsem et al. (April 2 issue)1 that “First-line treatment with cetuximab plus FOLFIRI [irinotecan, fluorouracil, and leucovorin], as compared with FOLFIRI alone, reduced the risk of progression of metastatic colorectal cancer.” My enthusiasm was tempered when I then read in the Results of the Abstract — and in the body of the article — that “There was no significant difference in the overall survival between the two treatment groups.” That caveat might well have been required to appear in the Conclusions of the Abstract, lest the wrong overly sanguine impression appear in other publications.
Abstract 2775: Development and characterization of a MEK1 inhibitor (AZD6244) sensitive childhood astrocytoma cell line
Authors: Adam W. Studebaker, Hemant K. Bid, Doris A. Phelps, Peter J. Houghton
Journal: Cancer Research (2014)

Abstract We previously characterized the development and reversal of acquired resistance to the MEK1 inhibitor AZD6244 in an in vivo model of childhood astrocytoma. The BT-40 astrocytoma xenograft model expresses mutated BRAFV600E and is highly sensitive to AZD6244, but acquires resistance, which can be overcome with the addition of the STAT3 inhibitor LLL12. The purpose of this current study was to establish and characterize a cell line derived from the xenograft model as well as develop an orthotopic mouse model. Sensitivity to AZD6244 and LLL12, expression-profiling assessment of MEK signature and compensatory pathways, and cytokine levels were assessed in the newly developed BT-40 cell line. The BT-40 cell line exhibited sensitivity to AZD6244 and LLL12 with IC50 values of 350nM and 1µM, respectively. Combination treatment was additive. Treatment of the cells with AZD6244 inhibited p-Erk and the mTOR downstream signaling molecule p-S6, while p-Akt, p-STAT3, p-4E-BP1 increased. Kinase expression arrays performed on cells treated with AZD6244 displayed a decrease in IL-1α, G-CSF, and IL-6 and an increase in CXCL10. The decrease in IL-6 was restored to baseline levels with the addition of LLL12. Interestingly, the JAK2 inhibitor AZD1480 failed to restore the IL-6 levels. The IL-6 results observed in the expression arrays were confirmed by ELISA, where AZD6244 decreased soluble IL-6 levels and LLL12, but not AZD1480, restored IL-6 levels to baseline. The BT-40 cell line, along with a cell line stably expressing luciferase (BT-40Luc), were implanted into the caudate putamen using stereotaxic guidance. The BT-40Luc cells exhibited exponential growth over time as evaluated with bioluminescent imaging. In conclusion, a cell line derived from a previously described in vivo model of childhood astrocytoma was developed that closely recapitulated our original findings in the xenograft model following treatment with the MEK1 inhibitor AZD6244. Furthermore, an orthotopic model of these cells was developed, which will allow us to characterize response to established and novel therapeutic agents. Supported by PHS award CA169368. Citation Format: Adam W. Studebaker, Hemant K. Bid, Doris A. Phelps, Peter J. Houghton. Development and characterization of a MEK1 inhibitor (AZD6244) sensitive childhood astrocytoma cell line. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2775. doi:10.1158/1538-7445.AM2014-2775
A monozygotic mirror-image twin pair with discordant psychiatric illnesses: a neuropsychiatric and neurodevelopmental evaluation
Authors: J B Lohr, H S Bracha
Journal: American Journal of Psychiatry (1992)

One piece of genetic evidence for the biological distinctness of schizophrenia and bipolar illness is the rarity of monozygotic twin pairs in which one twin suffers from schizophrenia and the other from bipolar disorder. The authors describe a pair of monozygotic mirror-image twins with discordant diagnoses, schizophrenia in one twin and bipolar or schizoaffective disorder in the other.
Comparison of the incidence and severity of extrapyramidal side effects with fluphenazine enanthate and fluphenazine decanoate
Authors: J Kane, F Quitkin, A Rifkin, D F Klein
Journal: American Journal of Psychiatry (1978)

Forty-nine schizophrenic outpatients stabilized on oral antipsychotic medication and procyclidine received 12.5 mg or 18.75 mg of fluphenazine enanthate or fluphenazine decanoate and were examined for extrapyramidal side effects one and two weeks later. Extrapyramidal side effects were present in 30 patients (61%) but were clinically significant in only 11 (22%). Fluphenazine enanthate produced more clinically significant extrapyramidal symptoms, particularly akathisia, than did fluphenazine decanoate.
Abstract 12792: Relationship Between Depression and Brain Injury in Heart Failure
Authors: Mary Ann Shinnick, Mary A Woo, Rajesh Kumar
Journal: Circulation (2014)

Introduction: Depression is common in heart failure (HF), and is an independent predictor of mortality and morbidity. MRI detected brain injury in many regions, including those associated with depressive symptoms (hippocampus, insular lobes). However, the association between depressive symptoms and documented brain injury has not been reported in HF. Methods: Using a 3.0-Tesla MRI scanner, we assessed brain tissue injury (DTI-based mean diffusivity [MD] procedures [damage indicated by increased diffusion/MD value]) and depressive symptoms (Beck Depression Inventory-II [BDI]; BDI scores &gt;17 indicate depression) in 16 HF (age 55.1 + 7.7 years; 12 males; LVEF 27.8 + 6.8) and 26 controls (age 49.7 + 10.8 years; 17 males). All HF subjects were NYHA Class I-II and were able to lie flat in an MRI scanner. Statistics consisted of Mann-Whitney U and Spearman’s Rho with significance set at p&lt;0.05. Results: No significant differences were found between the groups for age or BMI. A significant difference in depression scores were seen between the groups on the BDI (HF = 10.75 + 7.66; controls= 3.54 + 4.33; p &lt; 0.01) with only HF subjects exhibiting severe depression. Significant, positive correlations between brain injury and depression were detected in the right hippocampus, left insula, right frontal and right and left cerebellar areas (see Table 1). Discussion: This study reinforces the findings of depressive symptoms in HF patients but is the first study to show evidence of a correlation between damage to areas of emotion, cognition, and motor coordination in the brain and symptoms of depression. This study reveals a strong relationship between depression and brain damage in HF. Clinicians should not assume depression in HF is situational but may be due to brain injury.
Linking Transcriptional Elongation and Messenger RNA Export to Metastatic Breast Cancers
Authors: Shanchun Guo, Mohamed-Ali Hakimi, David Baillat, Xiaowei Chen, Michele J. Farber, Andres J.P. Klein-Szanto, Neil S. Cooch, Andrew K. Godwin, Ramin Shiekhattar
Journal: Cancer Research (2005)

Abstract The biochemical pathways that are disrupted in the genesis of sporadic breast cancers remain unclear. Moreover, the present prognosticating markers used to determine the prognosis of node-negative patient leads to probabilistic results, and the eventual clinical course is far from certain. Here we identified the human TREX complex, a multiprotein complex that links transcription elongation to mRNA transport, as culprit of aggressive human breast cancers. We show that whereas p84N5 (called hTREX84) is expressed at very low levels in normal breast epithelial cells, it is highly expressed in breast tumors. Importantly, hTREX84 expression correlates with tumor size and the metastatic state of the tumor progression. Reduction of hTREX84 levels in breast cancer cell lines by small interfering RNA result in inhibition of cellular proliferation and abrogation of mRNA export. These results not only identify hTREX84 as a prognosticator of breast cancer but also delineate human TREX complex as a target for therapeutic drugs against breast cancer.
Anorexia Nervosa
Authors: Joel Yager, Arnold E. Andersen
Journal: New England Journal of Medicine (2005)

A 17-year-old girl is taken to her physician by worried parents. Never overweight, in the past six months she became determined to reduce from her baseline weight of 59.1 kg. Her height is 1.7 m; body-mass index, 21. Through dieting and exercise, she lost 13.6 kg and stopped menstruating four months ago; her current body-mass index is 16. She denies having any problems and is annoyed that her parents, friends, and teachers are concerned. How should she be evaluated and treated?
Abstract 16566: The Carotid Atherosclerosis Score Predicts High-Risk Feature Development and Plaque Progression: A Prospective MRI Study
Authors: Dongxiang Xu, Daniel S Hippe, Hunter R Underhill, Thomas S Hatsukami, Minako Oikawa, Li Dong, Chun Yuan
Journal: Circulation (2011)

Background The Carotid Atherosclerosis Score (CAS) has been shown to stratify atherosclerotic disease severity in cross-sectional studies but its ability to predict future plaque development is unk...
Abstract 18740: Influence of Oral Progesterone Administration on QT Interval Response to Ikr Inhibition
Authors: James E Tisdale, Heather A Jaynes, Brian R Overholser, Kevin M Sowinski, David A Flockhart, Richard J Kovacs
Journal: Circulation (2014)

Introduction: Evidence from pre-clinical and human studies suggests that higher serum progesterone concentrations may be protective against drug-induced QT interval lengthening. Hypothesis: Oral progesterone administration attenuates QT interval response to I Kr inhibition. Methods: In this prospective, double-blind, crossover study, 15 healthy female volunteers ages 21-40 years were randomized to receive progesterone 400 mg or matching placebo orally once daily for 7 days timed to the menses phase of the menstrual cycle (between-phase washout period = 52 days). On day 7, a low dose of ibutilide (0.003 mg/kg) was infused over 10 minutes, after which QT intervals were recorded and blood samples serially collected for 12 hours post-infusion. Prior to the treatment phases, subjects underwent ECG monitoring for 12 hours to calculate individualized heart rate-corrected QT intervals (QT c I). Results: There was no significant difference in maximum serum ibutilide concentrations between the progesterone and placebo phases. (1291±910 vs 1328±718 pg/mL, p=0.87). ECG data are reported from lead II; results are similar from leads V 1 and V 5 . There was no significant difference in pre-ibutilide QT c I between the progesterone and placebo phases (Table). Maximum ibutilide-associated QT c I, maximum % change in QT c I, and % change in area under the effect (QT c I) curve during the first hour following ibutilide administration (AUEC 0-1 , s-hr) were significantly lower during the progesterone phase. Progesterone-associated adverse effects were mild, predominantly fatigue/general malaise. Ibutilide-associated adverse effects during the progesterone and placebo phases included bradycardia [3/15 (20%) vs 2/15 (13%)], burning at infusion site [1/15 (7%) vs 1/15 (7%)], and transient (&lt; 1 minute) Bazett’s-corrected QT c &gt; 500 ms [0/15 vs 1/15 (7%). Conclusions: Oral progesterone administration attenuates QT c I lengthening associated with I Kr inhibition
Abstract MP47: The Epidemiology of Sick Sinus Syndrome: The Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study
Authors: Paul N Jensen, Susan R Heckbert, Noelle N Gronroos, Lin Y Chen, Aaron R Folsom, Alvaro Alonso, Christopher deFilippi
Journal: Circulation (2013)

Objectives. Little is known about the epidemiology of sick sinus syndrome (SSS). The goals of this study were to determine the age and sex-specific incidence of SSS in white and black participants in the Atherosclerosis Risk In Communities (ARIC) study and the Cardiovascular Health Study (CHS), and to investigate associations of CV risk factors with incident SSS. Methods. From among ARIC (n=15,792) and CHS (n=5,888) participants, we included those who at baseline were free of prevalent atrial fibrillation and pacemaker, had a heart rate of ≥50bpm unless using beta blockers, and reported white or black race. Potential incident SSS cases were identified by ICD9 hospital discharge diagnosis code 427.81 and validated by medical record review. Incidence rates of SSS were calculated for each age-sex-race category. Age, sex, race, and clinic adjusted Cox models were used to assess associations of risk factors with incident SSS; estimates were combined across cohorts using fixed-effects meta-analysis. Results. At baseline, the average age of included participants (n=19,146) was 60 years. Traditional CV risk factors were more prevalent among blacks. During 324,505 person years of follow-up (mean 17 years), 291 incident SSS cases were identified, 246 in whites and 45 in blacks. Incidence estimates and associations with CV risk factors were similar in ARIC and CHS. SSS incidence increased with age (Table), and blacks had a 44% lower risk of SSS than whites (age, sex, and clinic adjusted HR: 0.56, 95%CI: 0.27, 1.20). In multivariate models, incident SSS was associated with greater BMI, height, NT-proBNP, cystatin C, and QRS interval, with lower heart rate and HDL cholesterol, and with prevalent hypertension, diabetes, right bundle branch block, CHD, and HF. Conclusions. The incidence of hospitalized SSS increased with age, and was lower for blacks than whites. Several modifiable CV risk factors were associated with incident hospitalized SSS.
Increasing incidence of anorexia nervosa in the female population of northeast Scotland
Authors: J M Eagles, M I Johnston, D Hunter, M Lobban, H R Millar
Journal: American Journal of Psychiatry (1995)

The aim of the study was to determine whether there has been an increase in the incidence of anorexia nervosa in the female population in the northeast of Scotland since the 1960s.Standardized diagnostic criteria were applied to the case records of female subjects who had been diagnosed as suffering from anorexia nervosa and had presented for the first time to psychiatric services between 1965 and 1991 or had been admitted for the first time to a general hospital between 1970 and 1991. Age-standardized annual incidence rates were calculated from 1965 through 1991. As a broad measure of severity, the weights of patients in 3 early years of the study, 1970-1972, were compared with those of patients in the last 3 years, 1989-1991.Over the 27-year period studied, 287 patients received confirmed diagnoses of anorexia nervosa, and the mean annual increase in incidence was 5.3%. The rate of increase was highly statistically significant. Comparison of weights at presentation showed a trend for patients presenting in 1970-1972 to be lighter than those presenting in 1989-1991.Rates of referral for female subjects with anorexia nervosa have greatly increased since the 1960s. These rates likely reflect a genuine increase in incidence, but the data suggest that less severely ill patients are now being referred.
Abstract 17758: Incidence and Predictors of Favourable Outcome 6 Months after an Out-of-Hospital Cardiac Arrest Treated with Hypothermia
Authors: Richel Zwerus, Irlando Andrade Ferreira, Ben Mooi, Jan Henk Dambrink, Henri van de Wetering, Martine Schutte, Esther Kuiper, Arnoud W van 't Hof
Journal: Circulation (2010)

Background: There is a high mortality rate in patients presenting with an out-of-hospital cardiac arrest (OHCA). Although not fully applied worldwide, Therapeutic Mild Hypothermia (TMH) is indicate...