tbuckley/cabot-search huggingface dataset:
Abstract 2811: A prostate stroma-derived profile is predictive of early relapse and reflects potential mechanisms of aggressive disease.
Authors: Zhenyu Jia, Farahnaz Rahmatpanah, Xin Chen, Michael McClelland, Dan Mercola
Journal: Cancer Research (2013)

Abstract The microenvironment of prostate cancer plays a major role in tumor initiation, growth, and metastatic spread. Using RNA expression data from fresh frozen human prostatectomies for which the clinical outcome was followed for over 5 years, we have developed a general approach to identify gene expression changes of the tumor-adjacent stroma that distinguishes aggressive prostate cancer cases from indolent cases. Highly significant gene associations were defined by correlating expression with Disease-free Survival (DFS) and also, separately, by comparing RNA expression between cases that remained disease free for at least 4 years following surgery with those cases that exhibited relapse within 1 year of surgery. A total of 193 highly significant genes were identified, of which 15 were common to the two approaches. These 15 genes were used to develop a PAM (Prediction Analysis for Microarrays)-based algorithm to classify new cases as indolent or aggressive and to provide a probability for each classification. The algorithm was tested on stroma-enriched samples from 47 new cases with known outcome with an accuracy of 87% [1]. A potential functional basis for some the genes associated with aggressive disease was suggested by the observation that p53 expression is decreased in aggressive disease whereas p53-target genes and cell cycle inhibitors including p21, GADD45A, and GADD45B are increased, which is a pattern others have noted as suggestive of senescence [2]. Increased IGFBP6, Tubulin alpha 1a, and Lamin A/C further suggest a senescence-associated secretory phenotype [3]. A potential secretory factor of known significance in the growth of prostate cancer (IGF-1/Somatomedin-C) has elevated RNA levels in the stroma of the same cases. These features argue that an accurate and general prediction of aggressiveness may be derived from the tumor microenvironment and may be composed of genes that have functional roles in bringing about aggressive disease. [1] Jia et al. 2012 PLoS ONE, 7(8):e41371 [2] Liebermann and Hoffman 2008 Journal of Molecular Signaling, 3:15 [3] Coppe et al. 2008 PLoS Biology, 6(12):e301 Citation Format: Zhenyu Jia, Farahnaz Rahmatpanah, Xin Chen, Michael McClelland, Dan Mercola. A prostate stroma-derived profile is predictive of early relapse and reflects potential mechanisms of aggressive disease. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2811. doi:10.1158/1538-7445.AM2013-2811 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
The genetic and neurobiologic compass points toward common signaling dysfunctions in autism spectrum disorders
Authors: Pat Levitt, Daniel B. Campbell
Journal: Journal of Clinical Investigation (2009)

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder with high heritability. Here, we discuss data supporting the view that there are at least two distinct genetic etiologies for ASD: rare, private (de novo) single gene mutations that may have a large effect in causing ASD; and inherited, common functional variants of a combination of genes, each having a small to moderate effect in increasing ASD risk. It also is possible that a combination of the two mechanisms may occur in some individuals with ASD. We further discuss evidence from individuals with a number of different neurodevelopmental syndromes, in which there is a high prevalence of ASD, that some private mutations and common variants converge on dysfunctional ERK and PI3K signaling, which negatively impacts neurodevelopmental events regulated by some receptor tyrosine kinases.
Long-Term Outcome in Patients Undergoing Surgical Repair of Tetralogy of Fallot
Authors: J G Murphy, B J Gersh, D D Mair, V Fuster, M D McGoon, D M Ilstrup, D C McGoon, J W Kirklin, G K Danielson
Journal: New England Journal of Medicine (1993)

Although corrective surgery for tetralogy of Fallot has been available for more than 30 years, the occurrence of late sudden death in patients in whom surgery was apparently successful remains worrisome.
Possible cellular mechanism for cerebral vasospasm after experimental subarachnoid hemorrhage in the dog.
Authors: D R Harder, P Dernbach, A Waters
Journal: Journal of Clinical Investigation (1987)

This study was undertaken to examine some of the cellular ionic mechanisms responsible for the cerebral vasospasm that occurs as a consequence of subarachnoid hemorrhage (SAH). After cisternal injection of autologous blood we documented spasm of the basilar artery upon angiography from 4 to 7 d postictus in six dogs. When these basilar arteries were isolated we observed marked membrane depolarization and enhanced electrical spike activity compared with controls. The slope of the membrane potential vs log [K]0 curve was significantly reduced in arteries exposed to SAH. Further analysis supported the concept that such altered muscle cell properties resulted from reduction in resting K+ conductance (gk). Exposure of arteries in vitro to nicorandil (10(-9)-10(-7)M) (a drug which acts by increasing gk) hyperpolarized the muscle cells and increased internal diameter. Infusion of nicorandil (3-5 micrograms/kg per min) to intact, anesthetized animals reversed, by 50%, the reduction in basilar artery diameter after experimental SAH.
Abstract 2446: Signaling event of alcohol-induced deregulation of Pol III genes in breast cancer cells
Authors: Shuping Zhong, Qingsong Zhang, Ganggang Shi
Journal: Cancer Research (2014)

Abstract Alcohol intake is consistently associated with an increased risk of breast cancer. Alcohol consumption is more pronounced in ER+ breast cancer cases than in ER- cases. However, its mechanism remains to be determined. We reported that alcohol induces Pol III gene (RNA polymerase III-dependent genes) transcription in vivo and in vitro. We continue to define novel and unexpected targets, MSK1 (mitogen- stress-activated protein kinase 1) and Brf1 (TFIIIB-related factor 1), in the alcohol-induced response. Our aim is to delineate the mechanisms regulating the processes of deregulation of Pol III genes, cell transformation and tumorgenesis through this alcohol-induced response. Brf1 specifically regulates Pol III gene transcription. Changes in Pol III gene and Brf1 expression tightly link to cell transformation and tumor formation. Alcohol-induced deregulation of Pol III genes may be fundamental to the development of breast cancer. We have reported that a) enhancement of Brf1 and Pol III gene expression is correlated with tumor formation in alcohol-fed mice; b) alcohol increases ERα activity to elevate Brf1 and Pol III gene expression; c) alcohol activates JNK1 to increase ERα and Brf1 expression; d) ethanol induces H3ph (histone H3 phosphorylation), e) H3ph elevates Brf1 expression. However, nothing is known about the role of MSK1 in transcription of Brf1 and Pol III genes. Analysis of signal event has revealed that ethanol markedly stimulates phosphorylation of MSK1 at serine 376 and threonine 581 in MCF-7 cells. Blocking MSK1 singling decreases cellular level of Brf1 expression and Pol III gene transcription. Further analysis indicates that MSK1 mediates ERα expression. Inhibition of MSK signaling decreases alcohol-induced ERE-Luc reporter activity. Repression of ERα expression by its siRNA reduces alcohol-induced anchorage-independent growth of MCF-7 cells. Our results have demonstrated that repression of MSK1 by its siRNA decreases colony formation of MCF-7 cells. Further analysis of ChIP assay indicates that ethanol treatment increases occupancy of ERα to Brf1 promoter. These results support the idea that alcohol activates MSK1 and enhances ERα and Brf1 expression resulting greater phenotypic changes. Together, our studies indicate that ethanol-induced MSK1 activation may play a critical role in alcohol-induced cell transformation and alcohol-associated ER+ breast cancer. *: The project is supported by NIH grants AA017288 and AA021114 to Shuping Zhong Citation Format: Shuping Zhong, Qingsong Zhang, Ganggang Shi. Signaling event of alcohol-induced deregulation of Pol III genes in breast cancer cells. [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 2446. doi:10.1158/1538-7445.AM2014-2446
Continuous Subcutaneous Insulin Infusion Does Not Provoke Significant Acute-Phase Response
Authors: Marcus A Sleightholm, Ruth Gallimore, Glenys A Tennent, Ian F Rowe, Eva M Kohner, Mark B Pepys
Journal: Diabetes Care (1986)

C-reactive protein (CRP), the classical acute-phase reactant, and serum amyloid A protein (SAA), the putative precursor of AA-type amyloid fibrils, were measured in 62 diabetic patients. They were all attending their regular clinic appointments and had been asymptomatic during the 2 wk preceding sampling. CRP and SAA levels were similar in 18 patients on continuous subcutaneous insulin infusion (CSII), 27 patients treated by conventional insulin therapy (CIT), nine treated by diet only, and eight treated by diet and oral hypoglycemic agents, and were almost entirely within the normal range. It is concluded that CSII does not provoke an acute-phase reaction in diabetic patients and, while caution should always be exercised with a new form of treatment, it does not seem likely that CSII will predispose to the development of reactive systemic amyloidosis.
New Techniques in External Cardiac Compressions
Authors: Nico F. March
Journal: JAMA (1980)

Despite the 8,000 drownings that occur annually in the United States, procedures for aquatic first aid are currently limited to mouth-to-mouth resuscitation, while cardiopulmonary resuscitation (CPR) must be delayed until the victim is transported to a solid surface for conventional closedchest cardiac compressions. We discuss techniques of positioning a victim on the rescuer's chest and initiating CPR, on site. Respiratory support was provided with a slightly modified scuba regulator, and procedures were tested on an instrumented aquatic CPR mannequin in the water and anesthetized dogs on land. Most results were within specified criteria for successful CPR. (<i>JAMA</i>244:1229-1232, 1980)
Rat dilated cardiomyopathy after autoimmune giant cell myocarditis.
Authors: M Kodama, H Hanawa, M Saeki, H Hosono, T Inomata, K Suzuki, A Shibata
Journal: Circulation Research (1994)

One of the possible causes of dilated cardiomyopathy is considered to be a sequel to myocarditis. Two mechanisms have been proposed in the process of progression of myocarditis into dilated cardiomyopathy: one is a persistent viral infection, and the other is an autoimmune myocardial injury. To clarify the possible part played by the autoimmune mechanism in the process, using an animal model, we investigated whether autoimmune myocarditis, exclusively not related to viral infection, might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with cardiac myosin fraction. Rats of the control group were immunized with ovalbumin. The clinical course was observed over 4 months. Six rats from the myosin-immunized group died during the acute phase and the healing phase, and all those rats had severe myocarditis. All rats that survived until the end of the study showed enlarged and discolored hearts. Aneurysmal changes were observed in the right ventricle during thoracotomy. The ratio of heart weight to body weight of the myosin-immunized group was significantly higher than that of the control group (3.36 +/- 0.49 versus 2.69 +/- 0.06 g/kg, respectively; P &lt; .005). The lengths of the anterior interventricular fissure and the posterior interventricular fissure of the hearts of the myosin-immunized group were significantly longer than those of the control group. The external diameter of the left ventricle of the myosin-immunized group was also significantly larger than that of the control group. Diffuse myocardial muscle loss and replacement fibrosis were the prominent histological findings of the rats of the myosin-immunized group.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of dosing frequency on the safety and efficacy of imiquimod 5% cream for treatment of actinic keratosis on the forearms and hands: a phase II, randomized placebo-controlled trial
Authors: K. Gebauer, S. Shumack, P.S.J. Cowen
Journal: British Journal of Dermatology (2009)

Clinical studies in cutaneous conditions other than actinic keratosis (AK) have revealed that the safety and efficacy profile of imiquimod is influenced by dosing frequency.To evaluate dosing frequency response of imiquimod 5% for treatment of AK.This was a phase II, multicentre, randomized, double-blind, placebo-controlled study. Adults with > or = 10 but < or = 50 clinical AKs, one of which was histologically confirmed, were randomized (4:1) to 2-6 packets of imiquimod or placebo cream applied to the dorsum of the forearms and hands once daily 2, 3, 5 or 7 times per week for 8 weeks. The primary endpoint was complete clearance of AKs in the treatment area at 8 weeks post-treatment.One hundred and forty-nine (94 men and 54 women) white subjects, with a mean +/- SD age of 71 +/- 10.2 years, were enrolled. Twenty-eight subjects (18.8%) discontinued from study: 0%, 3.1%, 6.9%, 30.0% and 33.3% withdrew for local skin reactions or adverse events in the combined placebo, and in the imiquimod 2, 3, 5 or 7 times per week groups, respectively. Seven serious adverse events occurred; none was related to the study drug. Median baseline lesions ranged from 38 to 40 for the treatment groups. Complete clearance was achieved in 0%, 3.2%, 6.9%, 3.3% and 6.7% of subjects, and partial clearance (> or = 75% lesion reduction) in 0%, 22.6%, 24.1%, 20.0% and 36.7% of subjects for the placebo and imiquimod 2, 3, 5 or 7 times per week regimens, respectively.Imiquimod 5% applied more frequently than 3 times per week to AKs was not well tolerated. Complete clearance rates were low; however, partial clearance rates increased with increased dosing frequency (P = 0.002).
Pathogenesis of Coffee-Induced Gastrointestinal Symptoms
Authors: Sidney Cohen
Journal: New England Journal of Medicine (1980)

Heartburn was the major gastrointestinal symptom associated with drinking coffee in 31 subjects. These symptomatic subjects had a diminished basal lower-esophageal-sphincter (LES) pressure, 8.3 +/- 1.1 mm Hg, as compared with the pressure in asymptomatic subjects, 19.4 +/- 1.3 mm Hg (P less than 0.01), in response to four separate doses of coffee. LES pressure increased in normal subjects but changed only minimally in the symptomatic group (P less than 0.01). Basal acid output was similar in both groups, but the maximal acid response to coffee was paradoxically greater in normal subjects, 20.9 +/- 3.6 meq per hour, than in the symptomatic group, 9.4 +/- 1.5 meq per hour (P less than 0.01). During coffee instillation into the stomach, 26 of 31 symptomatic subjects (83 per cent) had heartburn at the highest dosage. Cimetidine, but not placebo, reduced acid secretion and heartburn in response to coffee, suggesting that acid was required for the development of symptoms. These studies suggest that LES dysfunction and gastroesophageal reflux, rather than gastric hypersection, are responsible for the heartburn caused by coffee in certain susceptible persons.
A NEW METHOD OF VALVULAR GASTROSTOMY WITH A MUCOUS MEMBRANE LINING.
Authors: EDMUND ANDREWS
Journal: JAMA (1894)

The older methods of making a stomach fistula for feeding, in case of impassable stricture of the esophagus, seldom proves satisfactory. Food is easily introduced and digested, but can not be forced through the pylorus into the intestine, because at every contraction of the stomach for that purpose most of the contents are forced out through the fistula. Thus the food is lost, and many of the patients die of starvation. A mechanical rubber valve which we invented in one case partly overcame the difficulty, but did not permanently save the patient, Wetzel devised the following method: A small opening being made into the stomach, a rubber tube was inserted, and the outer portion of the tube laid along the external surface of the viscus, the stomach wall was folded over it for one and one-half inches and fastened with Lembert stitches, taking up only the peritoneal and muscular coats.
Inhibition of histone deacetylases triggers pharmacologic preconditioning effects against myocardial ischemic injury
Authors: T ZHAO, G CHENG, L ZHANG, Y TSENG, J PADBURY
Journal: Cardiovascular Research (2007)

Objectives Recent evidence has demonstrated the importance of histone deacetylases (HDAC) in the control of hypertrophic responses in the heart. However, it remains unknown whether inhibition of HDACs plays a role in myocardial ischemia and reperfusion (I/R) injury. We hypothesize that HDAC inhibition triggers preconditioning-like effects against I/R injury. Methods and results Isolated mouse hearts were perfused with 3 cycles of 5-minute infusion and 5-minute washout of 50 nM of trichostatin A (TSA), a potent inhibitor of HDACs to mimic early pharmacologic preconditioning. This was followed by 30 min of ischemia and 30 min of reperfusion. In addition, mice were treated with saline or TSA (0.1 mg/kg, i.p.) to investigate delayed pharmacologic preconditioning. Twenty-four hours later, the hearts were subjected to I/R. Ventricular function and infarct size were measured, and HDAC 3, 4 and 5 were assessed by Western blot and immunofluorescence. HDAC and p38 mitogen-activated protein kinase activities were determined. TSA produced marked improvements in post-ischemic ventricular function recovery and a reduction in infarct size in both early and delayed preconditioning. Cardioprotection elicited by TSA was abrogated by SB203580, an inhibitor of p38. HDAC 3, 4 and 5 proteins were detected in mouse myocardium. TSA treatments resulted in a significant inhibition of HDAC activity. HDAC inhibition caused a dramatic increase in phosphorylation of p38 and p38 activity. Notably, HDAC inhibition also resulted in remarkable acetylation of p38 at lysine residues. Conclusion These results suggest that inhibition of HDACs triggers pharmacologic preconditioning to protect the ischemic heart, which involves p38 activation.
THE PREDICTIVE VALUE OF THE RADIONUCLIDE FISTULOGRAM (RnF) IN ARTERIO-VENOUS FISTULAE (AVf) MALFUNCTION IN HEMODIALYSIS PATIENTS
Authors: I. S. Seo, W. M. Sy, W. Heneghan, A. Manoli, H. J. Kim
Journal: Clinical Nuclear Medicine (1984)

The predictive value of the RnF in AVf malfunction was determined in 45 hemodialysis patients (64 studies). Data obtained consisted of 2 sec. dynamic images (qualitative) and concurrent 64 x 64 byte mode acquisition with .5 sec/frame for 1 min. (quantitative) following 15–20 mCi of Tc99m compounds (MDP or Tc04) into the AVf. Fourteen patients with clinical suspicion of AVf malfunction were referred for RnF. Eleven (78.6%) were abnormal and 3 were normal, based on previously established qualitative (collaterals, back flow and/or stenosis) and quantitative (S1/S2 < 10%) criteria. Confirmatory contrast fistulogram (CnF) and surgical repair were done in 6/11. In three with normal studies, one had soft tissue abscesses near the venous orifice, another was later attributed to malposition of needles at hemodialysis and no cause was apparent in the third. In 31 clinically unsuspected patients who were referred for other studies (bone scintigraph & MUGA), seven (22.6%) had abnormal findings. Within two months surgical repairs were made in three, after CnF's confirmed AVf malfunction. The remaining four later developed signs of malfunction and are awaiting possible repair. Thus RnF, a simple, benign imaging procedure appears to have a high predictive value in documenting AVf malfunction in both symptomatic and in otherwise clinically unsuspected patients.
Government sued for 11 week delay in warning about aspirin
Authors: C. Dyer
Journal: BMJ (2002)

The UK government is being sued for negligence over an 11 week delay 15 years ago in issuing a warning about links between aspirin and Reye's syndrome.

In an action that opened in the High Court in London this week, lawyers for Amanda Smith, now aged 22, argued that the Committee on Safety of Medicines, the government's drug watchdog, was negligent in waiting until June 1986 to act after resolving in March that year that a warning …
Patients with Lynch Syndrome Mismatch Repair Gene Mutations Are at Higher Risk for Not Only Upper Tract Urothelial Cancer but Also Bladder Cancer
Authors: Sean C. Skeldon, Kara Semotiuk, Melyssa Aronson, Spring Holter, Steven Gallinger, Aaron Pollett, Cynthia Kuk, Bas van Rhijn, Peter Bostrom, Zane Cohen, Neil E. Fleshner, Michael A. Jewett, Sally Hanna, Shahrokh F. Shariat, Theodorus H. Van Der Kwast, Andrew Evans, Jim Catto, Bharati Bapat, Alexandre R. Zlotta
Journal: European Urology (2012)
M9 The prevalance and effects of smoking amongst patients attending a difficult asthma clinic: Abstract M9 Table 1.
Authors: DWY Ding, P Abraham, RK Yadavilli, BJ McDonough, S Mault, H Burhan
Journal: Thorax (2013)

<h3>Introduction</h3> The proportion of asthmatics that smoke is no different to that in the general population<sup>1,2</sup>. In patients with asthma, smoking has been associated with decline in pulmonary function, poor symptom control and reduced quality of life. <h3>Objectives</h3> To evaluate the differences in lung function, number of asthma admissions in the previous year, asthma control, quality of life and treatment between non-smokers, ex-smokers and current smokers attending an asthma clinic. Methods: Retrospective study of 92 patients from a dedicated asthma clinic. Patients were divided into three groups - Current Smoker, Ex-Smoker and Non-Smoker. Data was obtained for spirometry results, number of hospital admissions with asthma in the preceding year, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT) and British Thoracic Society (BTS) Step in Asthma Management. <h3>Results</h3> See Table 1. The majority of the patients attending the asthma clinic were non-smokers 62/92 (72%), and only 9/92 (10%) were current smokers. Baseline characteristics were similar in all three groups. There were significant differences in FEV<sub>1</sub>% (p &lt; 0.05) and FEV1/FVC ratio (p &lt; 0.01) among the groups, despite no statistical difference in the absolute FEV<sub>1</sub>, absolute FVC and FVC%. Interestingly, the groups were similar in terms of number of hospital admissions with asthma in the preceding year, AQLQ score, ACT score and BTS step in Asthma Management. <h3>Conclusions</h3> The proportion of smokers attending our asthma clinic is half that in the wider asthma population<sup>1</sup>. Smokers with asthma have lower FEV<sub>1</sub> as a% of predicted and FEV<sub>1</sub>/FVC ratio than non-smokers. There were, however, no differences in other spirometric parameters, the number of hospital admissions with asthma in the preceding year, AQLQ score, ACT score and BTS step in asthma management. Smoking cessation may result in subsequent improvements in asthma control and quality of life without the need for escalating treatment. <h3>References</h3> Eisner M. Yellin E. Trupin L and Blanc P. Asthma and smoking status in a population-based study of California adults. <i>Public Health Reports</i> Vol. 116<i>.</i> pp 48–157. 2. Asthma UK Everyday asthma out of control?Asthma UK, London 2005.