tbuckley/cabot-search huggingface dataset:
Choline and lecithin in the treatment of tardive dyskinesia: preliminary results from a pilot study
Authors: A J Gelenberg, J C Doller-Wojcik, J H Growdon
Journal: American Journal of Psychiatry (1979)

Tardive dyskinesia is thought to reflect increased dopaminergic activity of the central nervous system. To compensate for this by increasing CNS cholinergic tone, the authors administered oral choline and its natural dietary source, lecithin, to 5 men with mild to severe tardive dyskinesia in a nonblind trial. Both choline and lecithin increased serum choline levels and improved abnormal movements in all patients. Lecithin had fewer adverse effects.
Reviving academic medicine in Britain
Authors: S. Leinster
Journal: BMJ (2000)

Reducing error, improving safety Defensive culture of British medicine needs to changeEditor-It was brave to devote a whole issue to medical error 1 -how to recognise, how to investigate, how to analyse, and how to change systems to improve patient safety. 1 However, we regret that the edition was dominated by American studies, ignoring the British contribution of confidential inquiries and analyses of closed claims, which have significantly improved safety in some well defined areas of medical practice.In the United States the insurance industry provided the impetus for the study of adverse events, 2 and in Australia the government funded a similar study 3 because it was considering "no fault" compensation. 3 In the United Kingdom, for 25 years the Department of Health has financed all successful claims against NHS hospitals and their staff.As a result the need to take a British study beyond the pilot phase may not be supported. 4 Be that as it may, an important issue was not addressed in the BMJ.Behind each adverse event there is a patient, a doctor, and a doctor-patient relationship.A patient must be told when things have gone wrong.Every effort must be made to minimise the after effects, including financial compensation where necessary.Most patients wish to know in detail what happened and what is being done to reduce the possibility of a recurrence.And members of healthcare teams need mechanisms to come to terms with their fallibility.It is to be hoped that clinical governance will make a difference.Meanwhile a change in the ethos of medical practice is required, and it is to this end that Action for Victims of Medical Accidents has set up a group for doctors.Action for Victims of Medical Accidents is often regarded as dealing solely with compensation and litigation, but its raison d'être has always been to improve patient care.In February this year the doctors' group met informally to discuss how best to translate into practice the General Medical Council's requirements of "good medical practice when things go wrong." 5 We are determined to take our discussion forward and would welcome input from others who see the need to change the defensive and exclusive culture of British medicine.
Australian Hajj pilgrims’ knowledge, attitude and perception about Ebola, November 2014 to February 2015
Authors: A S Alqahtani, K E Wiley, H W Willaby, N F BinDhim, M Tashani, A E Heywood, R Booy, H Rashid
Journal: Eurosurveillance (2015)

Upon return from Hajj 2014, 150 Australian pilgrims were interviewed about their understanding of the Ebola epidemic. Most (89%, 134/150) knew of the epidemic before travelling and 60% (80/134) of those knew Ebola transmits through body fluids. Pilgrims who received pre-travel health advice were more conscious of Ebola (69% vs 31%, p = 0.01) and adhered better to hand hygiene after touching an ill person (68% vs 31%, p < 0.01). Mass media was the main information source (78%).
Abstract 2695: Comparison of the Full Stomach Test and a Pharmacological Test in Unmasking Brugada Syndrome
Authors: Takanori Ikeda, Satoru Yusu, Kentaro Nakamura, Hisaaki Mera, Atsuko Abe, Haruhisa Ishiguro, Hideaki Yoshino
Journal: Circulation (2006)

Background:  The electrocardiogram (ECG) feature of Brugada syndrome is dynamic and often concealed, but it is well known that sodium channel blockers may unmask its concealed forms. Recently, the full stomach test has been introduced as a novel diagnostic technique for identifying patients at risk of Brugada syndrome. In this study, we compared diagnostic value in unmasking Brugada syndrome between the full stomach test and a pharmacological test.   Methods:  We enrolled 57 consecutive patients with Brugada-type ECGs, showing persistent or transient coved ST segment elevation ≥0.2 mV in leads V1-V2. Pilsicainide, a pure sodium channel blocker, was used as a pharmacological test. Patients were given an oral dose of 100 mg of pilsicainide, and a 12-lead ECG was recorded 1 hour later. The pharmacological test was defined as positive when criteria from the consensus report on Brugada syndrome were fulfilled. For a full stomach test, patients had a large meal with beverages, and a 12-lead ECGs was recorded within 30 minutes after meals. The full stomach test was defined as positive when augmentation of ST segment elevation or visible T-wave variation in leads V1-V3 was observed after meals. We divided patients into two groups (i.e., high risk group [n=27] and indeterminate risk group [n=30]). Patients who had a history of life-threatening events and/or a family history of sudden death were defined as high risk group.   Results:  Both tests were successfully done in all patients. The pharmacological test was positive in 39 patients (68%) and the full stomach test was positive in 25 patients (44%). In both tests, the incidence (85% and 70%, respectively) of positive outcomes in high risk group was significantly higher than that (53% and 20%, respectively) of indeterminate risk group. In comparison between the two tests, the full stomach test was characterized by a more significant association with positive outcomes than that of the pharmacological test ( P =0.0004, odds ratio=9.5 vs.  P =0.02, odds ratio=5.0).   Conclusions:  In unmasking Brugada syndrome, a large meal is more effective than a sodium channel blocker. These data may support an idea that autonomic nerve modulation, particularly high vagal tone, plays an important role in arrhythmogenesis of the syndrome.
Abstract 499: Ca2+-dependent Tyrosine Kinase PYK2 Promotes Atherogenesis by Inducing Monocyte/Macrophage-Derived IL-1{beta} and MCP-1 Unmasked by Analysis of PYK2/ApoE Double Deficient Mice
Authors: Asako Katsume, Mitsuo Okigaki, Akihiro Matsui, Norifumi Urao, Hiroyuki Yamada, Hiroaki Matsubara
Journal: Circulation (2006)
Targeting estrogen signaling pathways for therapeutic intervention in non-small cell lung cancer.
Authors: Diana C. Marquez, Vei Mah, Lee Goodglick, Hermes Garbon, Olga Weinberg, Michael Fishbein, David Chia, Hsiao-Wang Chen, Steven Dubinett, David Seligson, Richard Pietras
Journal: Cancer Research (2006)

5351   Lung cancer is the most common cause of death from cancer in both male and female patients in the US. Survival from non-small cell lung cancer (NSCLC) is unacceptably low, and new therapies are needed. The etiology of NSCLC is not fully defined, but new studies suggest a role of estrogens in tumor progression (Cancer Res 62 : 2141, 2002; Steroids 70: 372, 2005). Further, estrogen receptor (ER) signaling is implicated in the rising incidence of NSCLC in women. This study assesses the notion that estrogen signaling may promote NSCLC growth, thus offering new therapeutic targets. Of 50 archival NSCLC tumors from postmenopausal women and from males assessed by immunohistochemistry (IHC), 82% and 79% show nuclear and/or extranuclear reactivity for ER-alpha and ER-beta, respectively, with NSCLC from both sexes expressing ER. Using lung tumor and normal tissue arrays, we are screening >500 lung cancers for ER and other signaling moieties to better define the molecular phenotype of lung cancers. In early studies with tissue from 60 patients, findings confirm ER expression in most NSCLC. In prior reports, we found specific, high-affinity estrogen binding in NSCLC cells, such as NIH-H23. Using Western blot methods, NSCLC cells showed predominant enrichment of a 59-kD protein that binds ER-beta antibody as well as enrichment of a 67-kD protein that binds antibody to ER-alpha. Transcripts for both ER forms are detected in NSCLC cells. Further, coactivator proteins, such as AIB1 and MNAR, that promote biologic effects of ER occur in NSCLC. Another arm of estrogen signaling is represented by the estrogen synthase, aromatase, an enzyme that elicits local production of estrogen to activate ER. We probed aromatase expression by IHC in >50 archival NSCLC tumors. Of these, 89% showed aromatase expression and, thus, may produce estrogens locally in lung tumors to promote growth. The level of aromatase measured by radiolabeled substrate assay suggests that activity is significantly higher in tumors than neighboring normal tissue (P
Levels of tonic BCR signaling predict response to the Btk inhibitor PCI-32765
Authors: Lee Honigberg, Jun Chen, Ashley Smith, Joseph Buggy
Journal: Cancer Research (2008)

2396  PCI-32765 is an orally bioavailable, covalent, and selective inhibitor of Bruton’s Tyrosine Kinase (Btk). We have shown previously that PCI-32765 inhibits B cell receptor (BCR) signaling, induces apoptosis in a subset of lymphoma cell lines, and suppresses tumor growth in B cell lymphoma xenograft models (Blood 110:475A). To identify biomarkers that correlate with response to PCI-32765 we began by investigating phosphorylation events in the BCR signal transduction pathway. We used a panel of phospho-specific antibodies that recognize activating phosphorylation sites in Syk, Btk, BLNK, PLC-γ1, PLC-γ2, Erk, and Akt and tested the effects of PCI-32765 on both basal phosphorylation and phosphorylation following BCR stimulation driven by cross-linking with anti-IgM or anti-IgG. We examined phosphorylation patterns in both a PCI-32765 sensitive cell line (DOHH2) and a PCI-32765 resistant cell line (Ramos). We found that PCI-32765 inhibits most BCR-stimulus induced phosphorylation events with similar potency in both cell lines. However, when we examined basal phosphorylation levels, we found higher basal phosphorylation in DOHH2 compared to Ramos, with phospho-Erk (pErk) in particular indicating higher levels of tonic signaling in DOHH2. Furthermore, PCI-32765 significantly decreased pErk levels in unstimulated DOHH2 cells (IC50
CEBPG transcription factor correlation with antioxidant and DNA repair genes in normal bronchial epithelial cells of individuals with and without bronchogenic carcinoma
Authors: D’Anna N. Mullins, Erin L. Crawford, Michael W. Harr, James C. Willey
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

140 

Cigarette smoking is the primary cause of bronchogenic carcinoma (BC), yet only 10-15% of heavy smokers develop BC, indicating a genetically determined variation in risk. In previous studies, transcript abundance values for several antioxidant and DNA repair genes were correlated in normal bronchial epithelial cells (NBEC) from non-BC individuals but correlation was reduced in NBEC from BC individuals. From these data, the hypothesis was made that in NBEC, antioxidant and DNA repair genes are co-regulated by one or more transcription factors and that individuals with sub-optimal regulation are at increased risk for BC. More than 10 transcription factors have recognition sites in the regulatory regions of each of the correlated antioxidant or DNA repair genes. Of these, only CEBPG was significantly (p < 0.0001) correlated with four of the genes (XRCC1, ERCC5, GSTP1, and SOD1) in non-BC individuals and significantly less correlated (p < 0.01) with these four genes in BC individuals. We concluded from this study that CEBPG is the transcription factor primarily responsible for regulating the transcription of key antioxidant and DNA repair genes in non-BC individuals, and further, that the heavy smokers selected for development of BC are those who have sub-optimal regulation of antioxidant and DNA repair genes by CEBPG. In order to establish a model with which to experimentally confirm the regulatory role of CEBPG, we measured the transcript abundance of CEBPG, XRCC1, ERCC5, GSTP1 and SOD1 in the H209, H460, H1437, BEP2D, H1355 and H23 lung cell lines. The greatest correlation observed in these cell lines was between CEBPG and the DNA repair gene ERCC5, with a correlation coefficient of 0.99 and a p value of <0.0001. In order to provide experimental confirmation of ERCC5 upregulation by CEBPG, CEBPG expression vector will be transfected into the cell line expressing the lowest level of CEBPG and ERCC5, followed by measurement of CEBPG protein and ERCC5 transcript abundance. Characterization of key antioxidant and DNA repair enzyme gene regulation in NBEC should lead to improved drug targets for chemoprevention and better biomarkers for risk, leading to improved early detection.
Physical health of people with severe mental illness
Authors: M. Phelan
Journal: BMJ (2001)

Over 60 years ago the BMJ reported an association between mental illness and poor physical health.1 Subsequent research, in many countries, has consistently confirmed that psychiatric patients have high rates of physical illness, much of which goes undetected. 2 3 Such investigations have led to calls for health professionals to be more aware of these findings and for better medical screening and treatment of psychiatric patients. So far there is no evidence that this is happening, and the excess illness and mortality continue unabated, with people being managed as psychiatric outpatients being nearly twice as likely to die as the general population.4

People with schizophrenia are subjected to the long term effects of antipsychotic medication and have high rates of substance misuse. Yet much of their excess mortality is due to natural causes. They eat less well, smoke more, and take less exercise than the general population.5 Smoking related fatal disease is …
Abstract #5348: Protein phosphatase 2A negatively regulates eukaryotic initiation factor 4E (eIF4E) phosphorylation and eIF4F activity
Authors: Yikun Li, Xuerong Wang, Fadlo Khuri, Shi-Yong Sun
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

The eukaryotic translation initiation factor 4E (eIF4E) is frequently overexpressed in various types of human cancers in relation to cellular transformation, tumorigenesis, and metastatic progression. Protein phosphatase 2A (PP2A) is known to function as a tumor suppressor. It is known that Mnks can phosphorylate eIF4E at serine 209 (S209). However, little is known about the regulation of eIF4E phosphorylation by PP2A and the biological function of its phosphorylation on the activity of the translation initiation complex eIF4F. In this study, we used both the PP2A specific inhibitor okadaic acid (OA) and small interfering RNA (siRNA) to demonstrate the role of PP2A in regulation of eIF4E phosphorylation. Inhibition of PP2A using either OA or PP2A siRNA strongly increased eIF4E phosphorylaiton at S209. In the presence of the Mnk inhibitor [CGP57380][1] or deficiency of Mnk genes, eIF4E phosphorylation by OA or PP2A siRNA was abolished, indicating the involvement of Mnks in PP2A-mediated regulation of eIF4E phosphorylation. Through immunoprecipitatiion of PP2A, we could detect phospho-Mnk1 in the precipitated complex by Western blotting, suggesting that PP2A physically interacts with Mnk1. Moreover, m7-GTP pull-down assays detected increased levels of eIF4G and phospho-eIF4E in the precipitated complex from PP2A siRNA-transfected cells compared to those from control siRNA-transfected cells. Accordingly, PP2A knockdown increased the expression of c-Myc, a protein subjected to regulation by a cap-dependent translation mechanism. These data collectively suggest that increased eIF4E phosphorylation by inhibition of PP2A triggers an enhanced assembly of the translation initiation complex eIF4F and thereby facilitates cap-dependent translation in human cancer cells. Taken together, we conclude that PP2A negatively regulates eIF4E phosphorylation, likely though inhibition of Mnk activity, and eIF4F activity or cap-dependent translation. Thus, our findings suggest a novel mechanism by which PP2A exerts its tumor suppressing function through inhibition of eIF4E-mediated cap-dependent protein translation. (Supported by the Georgia Cancer Coalition Distinguished Cancer Scholar award and NIH/NCI RO1 CA118450-01; SY Sun, and FR Khuri are Georgia Cancer Coalition Distinguished Cancer Scholars)

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5348.

 [1]: /lookup/external-ref?link_type=GENPEPT&access_num=CGP57380&atom=%2Fcanres%2F69%2F9_Supplement%2F5348.atom
Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat
Authors: Yong Lin, Jie-qing Wan, Guo-yi Gao, Yao-hua Pan, Sheng-hao Ding, Yi-ling Fan, Yong Wang, Ji-yao Jiang
Journal: Biomaterials (2015)
Cytosine β-D-Arabino-Furanoside (Ara-C), a DNA synthesis inhibitor, modulates p12DOC-1 expression and inhibits colorectal epithelial cell proliferation in human colorectal cancer with microsatellite instability.
Authors: Ziqiang Yuan, Anu G. Gaba, Anna Bennett, Tara S. Kent, Thomas K. Weber
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

2038 

Introduction: Recent studies have shown that 5-Fluorouracil-based adjuvant chemotherapy benefits patients with microsatellite stable (MSS) colorectal cancer (CRC), but not tumors exhibiting high frequency microsatellite instability (MSI) 1. We have previously demonstrated that decreased expression of p12DOC-1, the growth suppressor, is associated with colorectal epithelial proliferation and apoptosis arrest in human CRC with MSI 2. The purpose of this study was to test whether any of a set of known chemotherapeutic agents was capable of modulating p12DOC-1 expression in CRC cell lines with MSI. Material and Methods: p12DOC-1 expression in MSI CRC was studied using a Cancer Cell Line Profiling (CCLP) Array (Clontech) containing 702 complex cDNA samples from 26 different human cancer cell lines. The array cell lines were treated with a broad range of agents known to affect cell growth, differentiation and apoptosis. The profiling array was hybridized with a p12DOC-1 probe labeled with p32-dCTP. The intensity signal was assessed by Scion Image software. The array results were confirmed utilizing real-time RT-polymerase chain reaction (PCR). Cell cycle and apoptosis were also assessed by Fluorescence-Activated Cell Sorting assay in treated and untreated CRC cell lines. Results: Cytosine β -D-Arabino-Furanoside (Ara-C) was found to increase p12DOC-1 expression in 2 of 3 MSI CRC cell lines using the CCLP array. These results were also confirmed by real-time RT-PCR in 3 of 3 MSI CRC cell lines. When treated with Ara-C, these same 3 cell lines also demonstrated significantly decreased S phase and significantly increased apoptosis. There was no change in the p12DOC-1 expression, cell cycle S-phase or the apoptosis profile in the MSS CRC control cell line after treatment with Ara-C. Conclusion: These results demonstrate that the CCLP array provides a novel method for studying chemotherapy-induced alterations in differential gene expression. Our results also show that Ara-C modulates p12DOC-1 expression, inhibits colon epithelial cell proliferation and increases apoptosis in MSI CRC suggesting that Ara-C may play a unique therapeutic role in this disease. References: 1)Ribic CM, Sargent DJ, et al. Microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. NEJM. 349 July: 247-257, 2003. 2) Yuan ZQ, Kent TS, Weber TK. Differential expression of DOC-1 in microsatellite-unstable human colorectal cancer. Oncogene. 22: 6304-10, 2003.
Abstract 16397: HRV Analysis for Estimating Cardiac Function During Continuous-Flow LVAD Assistance
Authors: Satoru Kishimoto, Yuichiro Kishimoto, Kentaro Ohnuma, Mamoru Arakawa, Kazuma Date, Yoshiaki Takewa, Motonobu Nishimura, Eisuke Tatsumi
Journal: Circulation (2013)

Objective: We have been looking into the potential of heart rate variability (HRV), a well-known prognosis factor of heart disease, as a non-invasive assessment tool of cardiac function for heart f...
Association may be iatrogenic
Authors: M. Vickers
Journal: BMJ (1995)

incidence of both melanoma and non-melanoma skin cancer in people with pigmented skin is several times lower than that in people with less pigmented skin.2How do the authors explain an apparent lack of association of lymphoma and leukaemia with skin colour?The authors' reasoning is based on two assump- tions: that the incidence of skin cancer can be used as a marker of exposure to ultraviolet radiation and that immunosuppression has a dominant role in the pathogenesis of cancer induced by ultraviolet radiation.Both assumptions may be false.Al- though ultraviolet radiation has an unequivocal role in the development of skin cancer, the patho- genesis of skin neoplasms is multifactorial.This is shown by the fact that exposure to the sun increases the relative risk of melanoma by only a factor of two to five, which is not impressive in comparison with the 85-1269 times higher risk in people with two family members with melanoma.'Moreover, recent evidence suggests that, in the pathogenesis of skin cancer, mechanisms other than immunosuppression are relevant, such as mutagenesis and suppression of apoptosis induced by ultraviolet radiation.Factors other than expo- sure to ultraviolet radiation-for example, genetic predisposition-probably better explain the association between skin cancer and the occurrence oflymphoma and leukaemia.
Double induction strategy for acute myeloid leukemia: the effect of high-dose cytarabine with mitoxantrone instead of standard-dose cytarabine with daunorubicin and 6-thioguanine: a randomized trial by the German AML Cooperative Group.
Authors: Thomas Büchner, Wolfgang Hiddemann, Bernhard Wörmann, Helmut Löffler, Winfried Gassmann, Torsten Haferlach, Christa Fonatsch, Detlef Haase, Claudia Schoch, Dieter Hossfeld, Eva Lengfelder, Carlo Aul, Axel Heyll, Georg Maschmeyer, Wolf-Dieter Ludwig, Maria-Cristina Sauerland, Achim Heinecke
Journal: Blood (1999)