tbuckley/cabot-search huggingface dataset:
Monoamine oxidase A suppresses hepatocellular carcinoma metastasis by inhibiting the adrenergic system and its transactivation of EGFR signaling
Authors: Jun Li, Xiao-Mei Yang, Ya-Hui Wang, Ming-Xuan Feng, Xiao-Jin Liu, Yan-Li Zhang, Shuo Huang, Zheng Wu, Feng Xue, Wen-Xin Qin, Jian-Ren Gu, Qiang Xia, Zhi-Gang Zhang
Journal: Journal of Hepatology (2014)

Monoamine oxidase A (MAOA), a catecholamine neurotransmitter degrading enzyme, is closely associated with neurological and psychiatric disorders. However, its role in cancer progression remains unknown.Hepatocellular carcinoma (HCC) tissue arrays (n=254) were used to investigate the correlation between MAOA expression and clinicopathological findings. In vitro invasion and anoikis assays, and in vivo intrahepatic and lung metastasis models were used to determine the role of MAOA in HCC metastasis. Quantitative real-time PCR, western blotting, immunohistochemical staining and HPLC analysis were performed to uncover the mechanism of MAOA in HCC.We found that MAOA expression was significantly downregulated in 254 clinical HCC samples and was closely correlated with cancer vasoinvasion, metastasis, and poor prognoses. We then demonstrated that MAOA suppressed norepinephrine/epinephrine (NE/E)-induced HCC invasion and anoikis inhibition, and uncovered that the effects of NE/E on HCC behaviors were primarily mediated through alpha 1A (ADRA1A) and beta 2 adrenergic receptors (ADRB2). In addition to the canonical signaling pathway, which is mediated via adrenergic receptors (ADRs), we found that ADR-mediated EGFR transactivation was also involved in NE-induced HCC invasion and anoikis inhibition. Notably, we found that MAOA could synergize with EGFR inhibitors or ADR antagonists to abrogate NE-induced HCC behaviors.Taken together, the results of our study may provide insights into the application of MAOA as a novel predictor of clinical outcomes and indicate that increasing MAOA expression or enzyme activity may be a new approach that can be used for HCC treatment.
THE VEGETABLE NEUROTICS.
Authors: GEORGE FRANK BUTLER
Journal: JAMA (1899)

Dr. John Harley, in the Gulstonian lectures of three decades ago, discussed four vegetable neurotics which have occupied an important place in materia medica for more than twenty centuries, These drugs were conium, opium, belladonna, and hyoscyamus. To these might justly be added aconite and mandragora. These remedies have maintained practically their present positions since the renaissance of medicine. Aconite was very early employed by the monks in the treatment of fever, since under the canon law of the church they were forbidden to shed blood unless by special dispensation Consequently, around the ruins of the old monasteries are to be found wild plants of aconite, originally employed for medicine, and not for poison, as is usually, but uncharitably, believed. Of these vegetable neurotics, the one most abused has undoubtedly been opium, its chief alkaloid having produced more misery, though it has relieved more suffering, than any other agent in
Methods and approaches for assessing immunotoxicity: an overview.
Authors: J H Dean, M I Luster, G A Boorman
Journal: Environmental Health Perspectives (1982)

The goals of the National Toxicology Program as they relate to immunological evaluation in toxicity assessment are discussed. The advantages of immune function assays for defining cellular injury as subtoxic levels following exposure to general or immunocyte specific chemical toxicants are proposed. A comprehensive screening panel of immune function and host resistance assays is presented in the context of an NIEHS approach for immunotoxicity assessment and methods selection. A second panel for defining the mechanism underlying immunological injury was also described. Studies utilizing these methods and approaches are described in companion papers by our group.
Universal internalization or pluralistic micro-theories?
Authors: Heiko Hecht
Journal: Behavioral and Brain Sciences (2001)

In my response I revisit the question whether internalization should be conceived as representation or as instantiation. Shepard's ingenuity lies partly in allowing both interpretations. The down side of this facile generality of internalization is its immunity to falsification. I describe evidence from 3-D apparent motion studies that speak against geodesic paths in cases of underspecified percepts. I further reflect on the applicability of internalization to normal, well-specified perception, on the superiority of Gestalt principles, as well as on the evolutionary and developmental implications of the concept. The commentaries to the target article reveal an astonishing lack of agreement. This not only indicates that a satisfactory unifying theory explaining perception in the face of poorly specified stimuli does not exist. It also suggests that for the time being we have to be pluralistic and should treat internalization as a source of inspiration rather than as an irrefutable theory.
The mechanism of hyperpigmentation in seborrhoeic keratosis involves the high expression of endothelin-converting enzyme-1alpha and TNF-alpha, which stimulate secretion of endothelin 1
Authors: I. Manaka, S. Kadono, M. Kawashima, T. Kobayashi, G. Imokawa
Journal: British Journal of Dermatology (2001)

Seborrhoeic keratosis (SK) is a benign epidermal tumour with increased pigmentation. We have recently demonstrated that increased secretion of endothelin (ET)-1, a strong keratinocyte-derived mitogen and melanogen for human melanocytes, is intrinsically involved in the hyperpigmentation mechanism of SK.To examine whether the increased ET secretion results from cytokines that induce ET production and/or from differences in the processing of ET that lead to its final active, secreted form.We used immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine whether ET-inducing enzymes and/or cytokines are also highly expressed in SK.RT-PCR of mRNAs encoding interleukin (IL)-1alpha, tumour necrosis factor (TNF)-alpha and endothelin-converting enzyme (ECE)-1alpha demonstrated that there is an increased expression of TNF-alpha and ECE-1alpha mRNAs in SK, whereas the IL-1alpha transcript is rather downregulated in SK compared with that in perilesional normal epidermis. In parallel, immunohistochemical analysis of SK revealed marked immunostaining for TNF-alpha in basaloid cells at lower levels of the epidermis and in basal cells, and for ECE-1alpha in most basaloid and basal cells in comparison with their weak staining throughout the epidermis in perilesional normal controls. In contrast, immunostaining for IL-1alpha was almost negative in SK relative to distinctive staining throughout the epidermis in the perilesional normal controls.These findings suggest that the increased secretion of ET-1 leading to enhanced pigmentation in SK results from the co-ordinated increased expression of TNF-alpha and ECE-1alpha.
Report calls for public education on screening to ensure more realistic expectations
Authors: S. Mayor
Journal: BMJ (2009)

The public needs to be better informed about the purpose, benefits, and potential harms of screening programmes to overcome unrealistic expectations about what they can achieve, warns a report from UK clinicians and scientists.

The report, Making Sense of Screening , was developed in response to recent media coverage of celebrities who developed cancer, which has made screening a particularly emotive matter.

The treatment of the pop singer Kylie Minogue for breast cancer and the death from cervical cancer at the age of 27 of reality television star Jade Goody led to demands, and promises from politicians, that more people be included in screening programmes and that screening be offered more often, starting at a younger age and continuing for longer.

The authors of the report from Sense About Science, a …
The mechanisms of supraventricular tachycardia in children.
Authors: P C Gillette
Journal: Circulation (1976)

The mechanisms of supraventricular tachycardia were investigated in 35 children. Intracardiac electrograms including His bundle potentials were recorded. Atrial pacing and single premature atrial stimuli were performed in the right atrium. Tachycardia was observed and the mechanism elucidated in 33 patients. The atrial activation sequence during tachycardia, including high right atrium, low lateral right atrium, low septal right atrium, and left atrium, together with the ability to initiate or terminate the tachycardia with premature stimuli, were keys to defining the mechanisms. The observed mechanisms included atrioventricular (A-V) node reentry (8), sino atrial node re-entry (5), re-entry through manifest or concealed lateral anomalous pathway (8), re-entry through A-V node bypasses (3), and atrial (7) and junctional (2) ectopic focuses. The frequency of the various mechanisms of SVT is more varied in children than adults, with ectopic mechanisms being more common in children.
Death from Chloroform Anesthesia.
Authors: Wm. G. Kemper
Journal: JAMA (1902)

Manitowoc, Wis., Jan. 26, 1902. <h3>To the Editor:</h3> —In reading over Dr. Bayard Holmes' paper on "A Report of a Death from Chloroform Anesthesia," I am surprised at the ungenerous stand the Doctor takes in regard to the anesthetizer. After stating, "It has been my practice to have a skilful person administer chloroform, even if it necessitated an untried and even inexperienced physician as my first assistant," he, a little further on, takes comfort in the fact that the anesthetizer in this case was a stranger to him and untried. Why should that fact soothe, rather than trouble, his conscience, since he neglected to follow his own rule? The anesthetizer being a stranger and untried does not prove him unskilful. Death from anesthesia may be due to improper administration, to an unfavorable condition of the patient, or to an unfortunate choice of the anesthetic. It has been proven again and
As Production Goes Global, Drug Supply Faces Greater Risks to Safety, Quality
Authors: Bridget M. Kuehn
Journal: JAMA (2011)

ASUDDEN SPIKE IN ADVERSE EVENTS among patients receiving dialysis in 2007 led public health authorities on an international chase to find the cause. The culprit, it turned out, was adulterated heparin that contained oversulfated chondroitin sulfate, a substance added to the drug at some point during its production in China. The adulteration, estimated to have netted the individuals responsible for adding the chemical between $1 million and $3 million, led to hundreds of adverse events, including at least 3 deaths, according to a recent report (http://tinyurl.com/3nhypp7) from the Pew Health Group about the growing risks of substandard and counterfeit medications resulting from the increasing overseas production of pharmaceuticals and their ingredients. The Pew Health Group unveiled the report during a press briefing in July at which some stakeholders shared their views of the risks to drugs and offered support for many of the report’s recommendations.
Constitutive Human Telomerase Reverse Transcriptase Expression Enhances Regenerative Properties of Endothelial Progenitor Cells
Authors: Satoshi Murasawa, Joan Llevadot, Marcy Silver, Jeffrey M. Isner, Douglas W. Losordo, Takayuki Asahara
Journal: Circulation (2002)

Background— The regulatory molecule for cell life span, telomerase, was modified by human telomerase reverse transcriptase (hTERT) gene transfer to investigate its effect on regenerative properties of endothelial progenitor cells (EPCs) in neovascularization. Methods and Results— Telomerase activity was enhanced in hTERT-transduced EPCs (Td-TERTs) (1.2-fold versus no transduced EPCs [no-Td] and 1.2-fold versus GFP-transduced EPCs [Td/GFPs] at day 8; 5.2-fold versus no-Td and 4.8-fold versus Td/GFP at day 21, respectively) Mitogenic capacity in Td/TERTs exceeded that in Td/GFPs at day 8 (0.62±0.02 versus 0.53±0.01, respectively; P &lt;0.01). Vascular endothelial growth factor-induced cell migration in EPCs was markedly enhanced by hTERT overexpression (Td/TERTs versus Td/GFPs, 292±12 versus 174±6 cells, respectively; P &lt;0.01). hTERT overexpression has rescued EPCs from starvation-induced cell apoptosis, an outcome that was further enhanced in response to vascular endothelial growth factor. The colony appearance of totally differentiated endothelial cells (tdECs) was detected before day 30 only in Td/TERT, whereas no tdEC colonies could be detected in both Td/GFPs and no-Tds. Finally, we investigated in vivo transplantation of heterologous EPCs. Td/TERTs dramatically improved postnatal neovascularization in terms of limb salvage by 4-fold in comparison with that of Td/GFPs; limb perfusion was measured by laser Doppler (0.77±0.10 versus 0.47±0.06; P =0.02), and capillary density (224±78 versus 90±40 capillaries/mm 2 ; P &lt;0.01). Conclusions— These findings provide the novel evidence that telomerase activity contributes to EPC angiogenic properties; mitogenic activity, migratory activity, and cell survival. This enhanced regenerative activity of EPCs by hTERT transfer will provide novel therapeutical strategy for postnatal neovascularization in severe ischemic disease patients.
IVABRADINE PRODUCES SIMILAR IMPROVEMENT IN EXERCISE TOLERANCE AND HAEMODYNAMICS IN PATIENTS WITH MILD TO MODERATE MITRAL STENOSIS AS COMPARED TO METOPROLOL
Authors: Ram Kirti Saran, Varun Narain, Daljeet Kaur, Sharad Chandra, Rishi Sethi, Aniket Puri, Sudhanshu K. Dwivedi
Journal: Journal of the American College of Cardiology (2012)
THE ROLE OF PRIOR BALLOON AORTIC VALVULOPLASTY IN PATIENTS UNDERGOING TAVR: A PARTNER I SUBSTUDY ANALYSIS
Authors: Darshan Doshi, Mackram Eleid, Susheel Kodali, Kevin Greason, E. Murat Tuzcu, Ted Feldman, Ke Xu, Martin Leon, Charanjit Rihal
Journal: Journal of the American College of Cardiology (2014)
The Investigation of Dysphagia-Reply
Authors: Martin W. Donner
Journal: JAMA (1986)

<h3>In Reply.—</h3> Episodic observations made by staff members of The Johns Hopkins Swallowing Center of patients with symptoms of globus hystericus had revealed functional and structural disorders of the pharynx and esophagus. We therefore undertook a systematic study. The medical records of 167 patients seen at the center between May 1981 and December 1982 were retrospectively reviewed. Before referral, the symptoms of 23 patients had been attributed to psychogenic causes. Each patient was evaluated clinically, including detailed cineradiographic examination of the pharynx and esophagus. Additional procedures and consultations were performed as indicated. Of 15 patients categorized as having psychogenic dysphagia, three had significant structural lesions (peptic stricture, pharyngeal cancer, and aberrant subclavian artery), while two had pharyngeal dysfunction secondary to previously unrecognized neurological disease (motor neuron disease and choreiform disorder), one had pharyngeal dysfunction without an obvious underlying disease, and three had esophageal dysmotility. Of eight patients with a previous
Surgeons in the fields.
Authors: M Ryan
Journal: BMJ (1984)

<h3>SUMMARY</h3> CD8 T cell memory differentiation endows T cells with an ability to rapidly induce effector functions upon pathogen re-encounter. While it is well established that substantial epigenetic remodeling occurs during the effector stage of the immune response, the signaling events that imprint CD8 T cells with these stable epigenetic programs are not well-defined. To gain insight into the signaling determinants of effector-associated epigenetic programming among CD8 T cells, we explored the role of IL-12 in the imprinting of IFNg expression during human CD8 T cell priming. We observed that TCR-mediated stimulation of human naïve CD8 T cells is not sufficient to induce substantial demethylation of the IFNg promotor. However, TCR stimulation in the presence of the inflammatory cytokine, IL-12, resulted in significant and stable demethylation of the IFNg locus that was commensurate with an increase in IFNg expression. We further show that IL-12-associated demethylation of the IFNg locus is coupled to cell division through TET2-dependent passive demethylation in an <i>ex vivo</i> human CAR T cell model system and an <i>in vivo</i> immunologically competent murine system. Collectively, these data illustrate that IL-12 signaling promotes TET2-mediated effector epigenetic programming in CD8 T cells during the primary immune response and serve as proof of concept that signal 3 cytokines can be used to guide the induction of epigenetically regulated traits among T cells used for adoptive immunotherapies.
ETS-1 Oncogenic Activity Mediated by Transforming Growth Factor α
Authors: Chet E. Holterman, Aleksandra Franovic, Josianne Payette, Stephen Lee
Journal: Cancer Research (2010)

Abstract Inappropriate expression of Ets-1 is observed in a variety of human cancers, and its forced expression in cultured cells results in transformation, autonomous proliferation, and tumor formation. The basis by which Ets-1 confers autonomous growth, one of the primary hallmarks of cancer cells and a critical component of persistent proliferation, has yet to be fully explained. Using a variety of cancer cell lines, we show that inhibition of Ets-1 blocks tumor formation and cell proliferation in vivo and autonomous growth in culture. A screen of multiple diffusible growth factors revealed that inhibition of Ets-1 results in the specific downregulation of transforming growth factor α (TGFα), the proximal promoter region of which contains multiple ETS family DNA binding sites that can be directly bound and regulated by Ets-1. Notably, rescuing TGFα expression in Ets-1–silenced cells was sufficient to restore tumor cell proliferation in vivo and autonomous growth in culture. These results reveal a previously unrecognized mechanism by which Ets-1 oncogenic activity can be explained in human cancer through its ability to regulate the important cellular mitogen TGFα. Cancer Res; 70(2); 730–40
Reasons for Using and Failing to Use Sunscreen
Authors: Heike I. M. Mahler
Journal: JAMA Dermatology (2013)

Reasons for Using and Failing to Use Sunscreen: Comparison Among Whites, Hispanics, and Asian/Pacific Islanders in Southern CaliforniaMore detailed information about the perceived benefits of or barriers to adopting particular risk reduction behaviors would inform skin cancer prevention interventions.The primary purpose of this study was to compare the reasons for using and failing to use sunscreen among Asian/Pacific Islanders, Hispanics, and non-Hispanic whites.Methods | All procedures were reviewed and approved by the University of California, San Diego (UCSD), institutional review board.All participants provided written informed consent.The data were drawn from baseline questionnaires completed during 9 different experiments examining the efficacy of various sun protection interventions conducted at UCSD or at area beaches between 2000 and 2009.Although results of the interventions have been published previously (eg, Mahler and colleagues 1,2 ), participants' reasons for sunscreen use have not.Demographic information, UV exposure, sun protection behaviors, and reasons for using and failing to use sunscreen (Table 1) were assessed.To assess the latter, participants who
Lung volumes in normal Cantonese subjects: preliminary studies.
Authors: B Ching, P A Horsfall
Journal: Thorax (1977)

Measurements of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, functional residual capacity (FRC), total lung capacity (TLC), residual volume (RV), and RV/TLC ratio have been made in 331 normal Cantonese subjects (134 male and 197 female). The results have been expressed in multiple regression equations relating the volumes to age, height, and weight and have been compared with those of other workers. Lung volumes obtained in this study are in general lower for Chinese subjects than those reported for Caucasians. Similar findings for FVC were reported by Chuan and Chia (1969) in Singapore and by Wu and Yang (1962) in Taiwan. Significant differences, however, are noted for FRC, TLC, RV, and RV/TLC between our findings and those of Chuan and Chia. Our series is unbalanced because of an uneven distribution of age groups. In fact in none of the reported studies on Chinese subjects, including that of da Costa (1971), is the series large or balanced. Clearly, further research is required in this ethnic group to get more reliable predictive formulae for lung volumes.
Abstract A38: Whole methylome explorations of paired lung tumor and non-tumor clinical samples
Authors: Nandita Mullapudi, Masako Suzuki, Melissa Fazzari, Weiguo Han, Simon D. Spivack
Journal: Clinical Cancer Research (2012)

Abstract Background: Hypermethylation in specific candidate gene promoters has been found during progressive lung carcinogenesis. To explore common methylation events on a genome-wide scale in lung cancer, we analyzed the methylation profiles of paired NSCLC tumor and far adjacent non-tumor samples using the HELP-microarray assay, which yields information on 1.2 million fragments throughout the genome. Methods: The HELP (HpaII tiny fragment Enriched by Ligation mediated PCR) assay is based on the generation of restriction enzyme libraries generated by methylation sensitive (HpaII) and methylation insensitive (MspI) isoschizomers, in its second generation as a microarray platform. The assay lends itself to low starting amounts of DNA (3 ug) and robust assessment of methylation status by comparing ratios of HpaII- generated-fragments to MspI- generated fragments co-hybridized to a Nimbelgen custom high-density microarrays. The CCGG sites were weighted if neighboring CCGGs were methylated in same direction. Here, 24 pairs of tumor and adjacent non-tumor samples were analyzed using the HELP assay. Summary of results: At p = 5E-6, we identified 26,138 differentially methylated fragments (corresponding to 2 CpG sites each) in tumor versus non-tumor. The overall trend was consistent with genome-wide hypomethylation and locus specific hypermethylation (localized to CG-island containing promoters). We could identify both known and novel regions of the genome as well as specific gene-promoters that are hypermethylated in tumor versus non-tumor. Region # loci # signif loci T Hypomethyl T Hypermethyl Promoter 151,568 576 69% 31% Gene Body 551,628 9,817 62% 38% Intergenic 540,473 15,745 97% 3% Conclusion: An interrogation of methylation status of 1.2 million loci throughout the genome in paired lung tumor/non-tumor specimens reveals many more differential methylation events in gene bodies and intergenic regions than in promoters. That said, many previously unreported differentially-methylated gene promoters were identified. We are able to discover individual methylation events common across different clinical specimens. Based on a set of priors, we have narrowed down promoter-specific hypermethylation events for further validation using tagged Bisulfite Genomic Sequencing. We are also working on the integration of methylome date with other genome-wide epigenetic and expression data from the same clinical samples. [Funding source: NCI 1RC1 CA145422-01; 1K24-CA139054-01]