tbuckley/cabot-search huggingface dataset:
Transcriptional Coactivator <i>Drosophila Eyes Absent Homologue 2</i> Is Up-Regulated in Epithelial Ovarian Cancer and Promotes Tumor Growth
Authors: Lin Zhang, Nuo Yang, Jia Huang, Ronald J. Buckanovich, Shun Liang, Andrea Barchetti, Cristina Vezzani, Ann O'Brien-Jenkins, Jennifer Wang, Michelle Renee Ward, Maria C. Courreges, Stefano Fracchioli, Angelica Medina, Dionyssios Katsaros, Barbara L. Weber, George Coukos
Journal: Cancer Research (2005)

Epithelial ovarian cancer is the most frequent cause of gynecologic malignancy-related mortality in women. To identify genes up-regulated in ovarian cancer, PCR-select cDNA subtraction was done and Drosophila Eyes Absent Homologue 2 (EYA2) was isolated as a promising candidate. The transcriptional coactivator eya controls essential cellular functions during organogenesis of Drosophila. EYA2 mRNA was found to be up-regulated in ovarian cancer by real-time reverse transcription-PCR, whereas its protein product was detected in 93.6% of ovarian cancer specimens by immunohistochemistry (n = 140). EYA2 was amplified in 14.8% of ovarian carcinomas, as detected by array-based comparative genomic hybridization (n = 88). Most importantly, EYA2 overexpression was significantly associated with short overall survival in advanced ovarian cancer (n = 99, P = 0.0361). EYA2 was found to function as transcriptional activator in ovarian cancer cells by Gal4 assay and to promote tumor growth in vivo in xenograft models. Therefore, this study suggests an important role of EYA2 in ovarian cancer and its potential application as a therapeutic target.
The COOH-terminal End of R-Ras Alters the Motility and Morphology of Breast Epithelial Cells through Rho/Rho-Kinase
Authors: Ha-Won Jeong, Ju-Ock Nam, In-San Kim
Journal: Cancer Research (2005)

R-Ras has a high degree of sequence homology with Ras and other members of the Ras subfamily, including Rap, TC21, and M-Ras. Although R-Ras has been suggested to regulate cell adhesion, migration, and invasion, the biological mechanism has not been well assessed. In this report, we show that constitutively active R-Ras (38V) induces a more rounded cell shape and redistribution of focal adhesion, and enhances the phosphorylation of focal adhesion kinase and paxillin. Active R-Ras (38V) induces cell adhesion to type I collagen, but inhibits cell motility. In active R-Ras (38V) cells, the activity of RhoA is increased and accompanied with translocation to plasma membrane, but not that of Rac1 or Cdc42. In parallel, dominant-negative RhoA (N19RhoA) and Y27632, a specific inhibitor of Rho-associated kinase, dramatically reverse the rounded cell morphology to a spread cell shape and enhance motility. Furthermore, coincident with the formation of cortical actin filaments in active R-Ras (38V) cells, myosin light chain and Ser-19-phosphorylated myosin light chain mainly accumulate at the peripheral region, which is inhibited by the treatment of Y27632. Using H-Ras/R-Ras and R-Ras/H-Ras hybrid constructs, we show that the COOH-terminal region of R-Ras contains the specific signal for inducing changes in motility and morphology. Our results suggest that R-Ras in breast epithelial cells disrupts cell polarity and motility through the Rho/Rho-associated kinase pathway triggered by a signal from the COOH-terminal end of R-Ras.
Leptin reverses weight loss–induced changes in regional neural activity responses to visual food stimuli
Authors: Michael Rosenbaum, Melissa Sy, Katherine Pavlovich, Rudolph L. Leibel, Joy Hirsch
Journal: Journal of Clinical Investigation (2008)

Increased hunger and food intake during attempts to maintain weight loss are a critical problem in clinical management of obesity. To determine whether reduced body weight maintenance is accompanied by leptin-sensitive changes in neural activity in brain regions affecting regulatory and hedonic aspects of energy homeostasis, we examined brain region–specific neural activity elicited by food-related visual cues using functional MRI in 6 inpatient obese subjects. Subjects were assessed at their usual weight and, following stabilization at a 10% reduced body weight, while receiving either twice daily subcutaneous injections of leptin or placebo. Following weight loss, there were predictable changes in neural activity, many of which were reversed by leptin, in brain areas known to be involved in the regulatory, emotional, and cognitive control of food intake. Specifically, following weight loss there were leptin-reversible increases in neural activity in response to visual food cues in the brainstem, culmen, parahippocampal gyrus, inferior and middle frontal gyri, middle temporal gyrus, and lingual gyrus. There were also leptin-reversible decreases in activity in response to food cues in the hypothalamus, cingulate gyrus, and middle frontal gyrus. These data are consistent with a model of the weight-reduced state as one of relative leptin deficiency.
Adenosine deaminase inhibition and myocardial purine release during normoxia and ischaemia
Authors: P. W ACHTERBERG, E. HARMSEN, J. W. DE JONG
Journal: Cardiovascular Research (1985)

Journal Article Adenosine deaminase inhibition and myocardial purine release during normoxia and ischaemia Get access PETER W ACHTERBERG, PETER W ACHTERBERG * From the Cardiochemical Laboratory, Thoraxcenter, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands *To whom correspondence and reprint requests should be sent. Search for other works by this author on: Oxford Academic PubMed Google Scholar EEF HARMSEN, EEF HARMSEN From the Cardiochemical Laboratory, Thoraxcenter, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar JAN WILLEM DE JONG JAN WILLEM DE JONG From the Cardiochemical Laboratory, Thoraxcenter, Erasmus University Rotterdam, P.O.Box 1738, 3000 DR Rotterdam, The Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 19, Issue 10, October 1985, Pages 593–598, https://doi.org/10.1093/cvr/19.10.593 Published: 01 October 1985
Impact of a statewide intensive care unit quality improvement initiative on hospital mortality and length of stay: retrospective comparative analysis
Authors: A. Lipitz-Snyderman, D. Steinwachs, D. M. Needham, E. Colantuoni, L. L. Morlock, P. J. Pronovost
Journal: BMJ (2011)

<b>Objective</b> To evaluate whether implementation of the Michigan Keystone ICU project, a comprehensive statewide quality improvement initiative focused on reduction of infections, was associated with reductions in hospital mortality and length of stay for adults aged 65 or more admitted to intensive care units. <b>Design</b> Retrospective comparative study, using data from Medicare claims. <b>Setting</b> Michigan and Midwest region, United States. <b>Population</b> The study period (October 2001 to December 2006) spanned two years before the project was initiated to 22 months after its implementation. The study sample included hospital admissions for patients treated in 95 study hospitals in Michigan (238 937 total admissions) compared with 364 hospitals in the surrounding Midwest region (1 091 547 total admissions). <b>Main outcome measures</b> Hospital mortality and length of hospital stay. <b>Results</b> The overall trajectory of mortality outcomes differed significantly between the two groups upon implementation of the project (Wald test χ<sup>2</sup>=8.73, P=0.033). Reductions in mortality were significantly greater for the study group than for the comparison group 1-12 months (odds ratio 0.83, 95% confidence interval 0.79 to 0.87 <i>v</i> 0.88, 0.85 to 0.90, P=0.041) and 13-22 months (0.76, 0.72 to 0.81 <i>v</i> 0.84, 0.81 to 0.86, P=0.007) after implementation of the project. The overall trajectory of length of stay did not differ significantly between the groups upon implementation of the project (Wald test χ<sup>2</sup>=2.05, P=0.560). Group differences in adjusted length of stay compared with baseline did not reach significance during implementation of the project (−0.45 days, 95% confidence interval −0.62 to −0.28 <i>v</i> −0.35, −0.52 to −0.19) or during post-implementation months 1-12 (−0.59, −0.80 to −0.37 <i>v</i> −0.42, −0.59 to −0.25) and 13-22 (−0.67, −0.91 to −0.43 <i>v</i> −0.54, −0.72 to −0.37). <b>Conclusions</b> Implementation of the Keystone ICU project was associated with a significant decrease in hospital mortality in Michigan compared with the surrounding area. The project was not, however, sufficiently powered to show a significant difference in length of stay.
Randomized phase III study of S-1 alone versus S-1 plus docetaxel (DOC) in the treatment for advanced gastric cancer (AGC): The START trial.
Authors: Y. H. Kim, W. Koizumi, K. H. Lee, T. Kishimoto, H. C. Chung, T. Hara, J. Y. Cho, T. Nakajima, H. Kim, M. Fujii
Journal: Journal of Clinical Oncology (2011)

7 Background: S-1/cisplatin is regarded as one of the standard regimens in Japan by the SPIRITS trial, but cisplatin needs in-hospital treatment for hydration. Phase II data of S-1/DOC showed long survival by outpatient basis. Then we hypothesized that S-1/DOC can be the standard regimen for AGC as outpatient basis. Methods: This is a prospective, multinational randomized phase III study in pts with AGC. Arm A: pts receive S-1 (40mg/m 2 ) twice daily 14 days followed by 7 days rest plus DOC (40 mg/m 2 ) iv on day 1. Arm B: pts receive S-1 28days followed by 14 days rest. Eligibility criteria included measurable/nonmeasurable AGC, age 20–79 and no prior chemotherapy. Primaryendpoint was OS, secondary endpoints were TTP, RR and safety. Based on planned sample size of 628 pts, the trial was designed tohave 90% power to detect an improvement in OS from 300 to 400 days. The accrual period was 3 years with 2 years follow up. Results: 639 pts (Arm A/B, 316/323) were registered and the eligible pts were 635 (314/321).The MST for Arm A was 386 and for Arm B was 327days. The OS for Arm A was not superior to Arm B (log-rank p = 0.1595, HR: 0.88). The TTP for Arm A was 160 and for Arm B was 126 days. The TTP for Arm A was significantly superior to Arm B (log-rank p &lt; 0.0003, HR: 0.74). RR of Arm A was significantly higher than Arm B (36.0%/ 24.4%, p = 0.01). By subset analysis of OS in pre-stratified nonmeasurable AGC, the MST for Arm A was significantly superior to for Arm B (523/335, log-lank p = 0.018). Most common grade 3/4 toxicities were: neutropenia, 31.4% vs. 4.4%; leucopenia, 22.1% vs. 2.5% and anorexia; 15.4% vs. 12.1%. Conclusions: The combination ofS-1/DOC did not meet primary endpoint of OS, but of OS in nonmeasurable group and TTP of the S-1/DOC was significantly superior to that of the S-1 alone. We supposed that recent development of the second-line chemotherapy was influenced to our results. This regimen can be regarded as one of the standard treatments for AGC as outpatient basis. [Table: see text]
Age- and Gender-specific Risk Factors Associated with Difficult-to-treat Asthma Phenotype among Japanese Asthmatic Patients
Authors: Y. Fukutomi, M. Taniguchi, T. Tsuburai, N. Higashi, S. Tatsuno, H. Tanimoto, C. Oshikata, E. Ono, K. Sekiya, N. Turikisawa
Journal: Journal of Allergy and Clinical Immunology (2009)
Evolution of Bitter Taste Receptors in Humans and Apes
Authors: Anne Fischer, Yoav Gilad, Orna Man, Svante Pääbo
Journal: Molecular Biology and Evolution (2004)

Bitter taste perception is crucial for the survival of organisms because it enables them to avoid the ingestion of potentially harmful substances. Bitter taste receptors are encoded by a gene family that in humans has been shown to contain 25 putatively functional genes and 8 pseudogenes and in mouse 33 putatively functional genes and 3 pseudogenes. Lineage-specific expansions of bitter taste receptors have taken place in both mouse and human, but very little is known about the evolution of these receptors in primates. We report the analysis of the almost complete repertoires of bitter taste receptor genes in human, great apes, and two Old World monkeys. As a group, these genes seem to be under little selective constraint compared with olfactory receptors and other genes in the studied species. However, in contrast to the olfactory receptor gene repertoire, where humans have a higher proportion of pseudogenes than apes, there is no evidence that the rate of loss of bitter taste receptor genes varies among humans and apes.
Sex, Death, and the Diagnosis Gap
Authors: C. Noel Bairey Merz
Journal: Circulation (2014)

C ardiovascular disease (CVD) continues to kill more women than men annually in the United States, 1 a female death epidemic that emerged rapidly in 1984 and persists in 2014.This mortality shift was not accompanied by explanatory sex-specific changes in known risk factors 2 and was too rapid to be caused by sex-linked genetic/genomic change.Although the aging epidemic combined with female longevity is a convenient putative explanation, CVD death rates have actually declined in older women, concomitant with the declines in older and young men, compared with an increase in younger women. 2 Although overall female CVD death rates began to decline in the 2000s, 1 we continue to have both a surplus of female deaths and an absence of understanding as to root causes.
Steroids cause osteoporosis
Authors: S Paget
Journal: Annals of the Rheumatic Diseases (2002)

Excellent treatment options exist. So why don't we all prevent or treat it?

When doctors institute steroids for any illness and for any length of time, they take on a lifelong responsibility to that patient to both taper the drug as quickly as is possible and safe and prevent or treat the many well recognised steroid related side effects.1 This is particularly true when steroid treatment lasts for more than one month and certainly for many months or years. Rheumatologists have a particular accountability because of the 1% of the population who are receiving long term steroids, most have rheumatological disorders.2,3 Further, rheumatologists should have the best understanding of when the treatment course will be prolonged, the profound and negative physiological impact of steroids on bone, and the need to deal with this important issue in both men and women.4,5

A recent topic search for steroid-induced osteoporosis (SIO) yielded 79 000 articles since 1966 and 13 000 since l998, most of which focused on the pathogenesis, clinical manifestations, and treatment of SIO. Despite the saturation publication on this topic for years, doctors do …
Randomized phase III trial comparing cisplatin–etoposide to carboplatin–paclitaxel in advanced or metastatic non-small cell lung cancer
Authors: C.P. Belani, J.S. Lee, M.A. Socinski, F. Robert, D. Waterhouse, K. Rowland, R. Ansari, R. Lilenbaum, R.B. Natale
Journal: Annals of Oncology (2005)
Genetic Susceptibility to Asthma — Bronchial Hyperresponsiveness Coinherited with a Major Gene for Atopy
Authors: Dirkje S. Postma, Eugene R. Bleecker, Pamela J. Amelung, Kenneth J. Holroyd, Jianfeng Xu, Carolien I.M. Panhuysen, Deborah A. Meyers, Roy C. Levitt
Journal: New England Journal of Medicine (1995)

Bronchial hyperresponsiveness, a risk factor for asthma, consists of a heightened bronchoconstrictor response to a variety of stimuli. The condition has a heritable component and is closely related to serum IgE levels and airway inflammation. The basis for these relations is unknown, as is the mechanism of genetic susceptibility to bronchial hyperresponsiveness. We attempted to define the interrelation between atopy and bronchial hyperresponsiveness and to investigate the chromosomal location of this component of asthma.
Holiday Gynecomastia Related to Marijuana?
Authors: Armin E. Heufelder
Journal: Annals of Internal Medicine (1993)

Letters1 August 1993Holiday Gynecomastia Related to Marijuana?Armin E. Heufelder, MDArmin E. Heufelder, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-3-199308010-00035 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Marijuana use is a well-recognized factor contributing to the development of gynecomastia. However, in the patient we examined, we were unable to detect any evidence of such use despite a careful history and physical examination. Although we cannot rule out this possibility, we believe that marijuana use is an unlikely explanation for this patient's gynecomastia. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1993Volume 119, Issue 3Page: 253KeywordsAddictionMarijuana Issue Published: 1 August 1993 CopyrightCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Care of children in general practice.
Authors: G C Jenkins
Journal: BMJ (1979)

In our survey2 we found in the five types of schools where a cold buffet was offered that the average food per plate provided 10-25 IO less than the hot meal in the same school both for energy and for protein.At that time we were considering whether or not the target was being achieved and this greater shortfall with the cold buffet indicated that it was not getting as near the target as was the hot meal.However, since children vary so much in their needs perhaps, when offered a choice, they select what they need rather than what the nutritionist thinks that, on average, they ought to have.On this basis there might be an actual saving in the cost of food if the children were offered a choice instead of the traditional approach.Cerainly sandwiches, beans on toast, and similar snacks which are usually looked down on can be as nutritious as a traditional hot meal.
Cryptotanshinone Inhibits Constitutive Signal Transducer and Activator of Transcription 3 Function through Blocking the Dimerization in DU145 Prostate Cancer Cells
Authors: Dae-Seop Shin, Hye-Nan Kim, Ki Deok Shin, Young Ju Yoon, Seung-Jun Kim, Dong Cho Han, Byoung-Mog Kwon
Journal: Cancer Research (2008)

Abstract Because signal transducer and activator of transcription 3 (STAT3) is constitutively activated in most human solid tumors and is involved in the proliferation, angiogenesis, immune evasion, and antiapoptosis of cancer cells, researchers have focused on STAT3 as a target for cancer therapy. We screened for natural compounds that inhibit the activity of STAT3 using a dual-luciferase assay. Cryptotanshinone was identified as a potent STAT3 inhibitor. Cryptotanshinone rapidly inhibited STAT3 Tyr705 phosphorylation in DU145 prostate cancer cells and the growth of the cells through 96 hours of the treatment. Inhibition of STAT3 Tyr705 phosphorylation in DU145 cells decreased the expression of STAT3 downstream target proteins such as cyclin D1, survivin, and Bcl-xL. To investigate the cryptotanshinone inhibitory mechanism in DU145 cells, we analyzed proteins upstream of STAT3. Although phosphorylation of Janus-activated kinase (JAK) 2 was inhibited by 7 μmol/L cryptotanshinone at 24 hours, inhibition of STAT3 Tyr705 phosphorylation occurred within 30 minutes and the activity of the other proteins was not affected. These results suggest that inhibition of STAT3 phosphorylation is caused by a JAK2-independent mechanism, with suppression of JAK2 phosphorylation as a secondary effect of cryptotanshinone treatment. Continuing experiments revealed the possibility that cryptotanshinone might directly bind to STAT3 molecules. Cryptotanshinone was colocalized with STAT3 molecules in the cytoplasm and inhibited the formation of STAT3 dimers. Computational modeling showed that cryptotanshinone could bind to the SH2 domain of STAT3. These results suggest that cryptotanshinone is a potent anticancer agent targeting the activation STAT3 protein. It is the first report that cryptotanshinone has antitumor activity through the inhibition of STAT3. [Cancer Res 2009;69(1):193–202]
Insomnia, Self-Medication, and Relapse to Alcoholism
Authors: Kirk J. Brower, Michael S. Aldrich, Elizabeth A.R. Robinson, Robert A. Zucker, John F. Greden
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: This study was an investigation of the frequencies of insomnia and its self-medication with alcohol in a group of alcoholic patients, as well as the relationship of these variables to alcoholic relapse. METHOD: The subjects were 172 men and women receiving treatment for alcohol dependence. They completed a sleep questionnaire, measures of alcohol problem severity and depression severity, and polysomnography after at least 2 weeks of abstinence. RESULTS: On the basis of eight items from the Sleep Disorders Questionnaire, 61% of the subjects were classified as having symptomatic insomnia during the 6 months before treatment entry. Compared to patients without insomnia, patients with insomnia were more likely to report frequent alcohol use for sleep (55% versus 28%), had significantly worse polysomnographic measures of sleep continuity, and had more severe alcohol dependence and depression. Among 74 alcoholics who were followed a mean of 5 months after treatment, 60% with baseline insomnia versus 30% without baseline insomnia relapsed to any use of alcohol, a significant difference. Insomnia remained a robust predictor of relapse after application of logistic regression analysis to control for other variables. A history of self-medicating insomnia with alcohol did not significantly predict subsequent relapse. CONCLUSIONS: The majority of alcoholic patients entering treatment reported insomnia symptoms. Given the potential link between insomnia and relapse, routine questions about sleep in clinical and research settings are warranted.
BEAMing Up Personalized Medicine: Mutation Detection in Blood
Authors: Andrea L. Richardson, J. Dirk Iglehart
Journal: Clinical Cancer Research (2012)

BEAMing is a feasible, accurate, and sensitive method for detection of PIK3CA mutations in circulating tumor DNA in blood. Mutation status of PIK3CA may change between primary tumor and recurrence. The results suggest a new approach for noninvasive determination of current mutation status in patients with metastatic disease.