tbuckley/cabot-search huggingface dataset:
Abstract 5183: Modulation of miR-29 expression by alpha-fetoprotein is linked to the hepatocellular carcinoma epigenome
Authors: Sonya T. Parpart, Stephanie Roessler, Fei Dong, Vinay Rao, Junfang Ji, Lun–Xiu Qin, Qing–Hai Ye, Zhao–You Tang, Hu–Liang Jia, Xin Wei Wang
Journal: Cancer Research (2014)

Abstract Globally, hepatocellular carcinoma (HCC) accounts for 70-85% of primary liver cancers and ranks second in the leading cause of male cancer death. Serum alpha-fetoprotein (AFP), normally highly expressed in the liver only during fetal development, is reactivated in 60% of HCC tumors and associated with poor patient outcome. We hypothesize that AFP+ and AFP- tumors differ biologically. Using microarray-based global microRNA profiling in 223 HCC patients, we found that members of the miR-29 family were the most significantly (p&amp;lt;0.001) down-regulated miRNAs in AFP+ tumors. Consistent with miR-29's role in targeting DNA methyltransferase 3A (DNMT3A), a key enzyme regulating DNA methylation, we found a significant inverse correlation (p&amp;lt;0.001) between miR-29 and DNMT3A gene expression suggesting that they might be functionally antagonistic. Moreover, global DNA methylation array profiling reveals that AFP+ and AFP- HCC tumors have distinct global DNA methylation patterns and that increased DNA methylation is associated with AFP+ HCC. Interestingly, miR-29 family physiological expression is low in mouse embryonic livers but gradually increases after birth. This is in contrary to AFP expression, which dramatically decreases after birth. Experimentally, we demonstrated that increased AFP expression, or conditioned media from AFP expressing HCC cells, inhibits miR-29a expression in AFP- HCC cells. AFP also inhibited transcription of the miR-29a/b-1 locus and this effect is mediated through c-MYC binding to the miR-29a/b-1 promoter. Our findings indicate that tumor biology differs considerably between AFP+ HCC and AFP- HCC and that AFP is a functional antagonist of miR-29, which may contribute to global epigenetic alterations and poor prognosis in HCC. Citation Format: Sonya T. Parpart, Stephanie Roessler, Fei Dong, Vinay Rao, Junfang Ji, Lun–Xiu Qin, Qing–Hai Ye, Zhao–You Tang, Hu–Liang Jia, Xin Wei Wang. Modulation of miR-29 expression by alpha-fetoprotein is linked to the hepatocellular carcinoma epigenome. [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 5183. doi:10.1158/1538-7445.AM2014-5183
A Case-Crossover Analysis of Out-of-Hospital Coronary Deaths and Air Pollution in Rome, Italy
Authors: Francesco Forastiere, Massimo Stafoggia, Sally Picciotto, Tom Bellander, Daniela D'Ippoliti, Timo Lanki, Stephanie von Klot, Fredrik Nyberg, Pentti Paatero, Annette Peters, Juha Pekkanen, Jordi Sunyer, Carlo A. Perucci
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Out-of-hospital coronary heart disease death is a major public health problem, but the association with air pollution is not well understood.We evaluated the association between daily ambient air pollution levels (particle number concentration [PNC]--a proxy for ultrafine particles [diameter < 0.1 microm], mass of particles with diameter less than 10 microm [PM10]; CO, NO2, and O3) and the occurrence of fatal, nonhospitalized coronary events.Subjects were 5,144 out-of-hospital fatalities (410-414, International Classification of Diseases-9; 1998-2000) who had been residents of Rome. Hospitalizations during the 3 yr before death were considered to identify comorbidities (e.g., diabetes, hypertension, heart failure, dysrhythmia, chronic obstructive pulmonary disease). Statistical analyses were performed using a case-crossover design.The association with out-of-hospital coronary deaths was statistically significant for PNC, PM10, and CO. Air pollution on the day of death had the strongest effect (e.g., 7.6% increase [95% confidence interval, 2.0-13.6%]) for an interquartile range of PNC, 27,790 particles/cm3. The 65-74- and 75+-yr age groups were at higher risk than the 35-64-yr age group, and there was a suggestion of effect modification for people with hypertension and chronic obstructive pulmonary disease.Air pollutants originating from combustion processes, including ultrafine particles, are related to fatal, nonhospitalized coronary events. The effect is stronger among people over 65 years of age, but is not limited to a group with a specific comorbidity.
Beneficial Effects of Amlodipine in a Murine Model of Congestive Heart Failure Induced by Viral Myocarditis
Authors: Wei Zhong Wang, Akira Matsumori, Takehiko Yamada, Tetsuo Shioi, Ikutaro Okada, Shigeo Matsui, Yukihito Sato, Hiroshi Suzuki, Kohei Shiota, Shigetake Sasayama
Journal: Circulation (1997)

Background Although calcium channel blockers have not been shown to be beneficial for the treatment of patients with heart failure, a recent clinical trial demonstrated a favorable effect of amlodipine on the survival of patients with heart failure resulting from nonischemic dilated cardiomyopathy. We investigated the effects of amlodipine on a murine model of congestive heart failure induced by the M variant of encephalomyocarditis virus (EMCV). Methods and Results Four-week-old male DBA/2 mice were inoculated with EMCV and administered amlodipine, diltiazem, or vehicle PO for 2 weeks. The heart weight–to–body weight ratio and the histopathological grades of myocardial lesions were significantly lower and survival was significantly increased in the amlodipine-treated group ( P &lt;.01, P &lt;.05, and P &lt;.05, respectively) than in the control group. In vitro, amlodipine added to murine J774A.1 macrophages concomitant with EMCV inhibited nitrite formation in a concentration-dependent manner, but diltiazem did not. Furthermore, N G -monomethyl- l -arginine, an inhibitor of NO synthesis, decreased myocardial lesions significantly in this murine model. Immunohistochemistry revealed that the number of cells stained with antibody against an inducible NO synthase decreased significantly in the amlodipine-treated group compared with that in the control group ( P &lt;.01). Conclusions Amlodipine appears to have a protective effect against myocardial injury in this animal model of congestive heart failure. The therapeutic effect of amlodipine may be in part resulting from inhibition of overproduction of NO.
microRNA Regulation of Inflammatory Responses
Authors: Ryan M. O'Connell, Dinesh S. Rao, David Baltimore
Journal: Annual Review of Immunology (2012)

The mammalian inflammatory response is a rapid and complex physiological reaction to noxious stimuli including microbial pathogens. Although inflammation plays a valuable role in combating infection, its dysregulation often occurs in people and can cause a variety of pathologies, ranging from chronic inflammation, to autoimmunity, to cancer. In recent years, our understanding of both the cellular and molecular networks that regulate inflammation has improved dramatically. Although much of the focus has been on the study of protein regulators of inflammation, recent evidence also points to a critical role for a specific class of noncoding RNAs, called microRNAs (miRNAs), in managing certain features of the inflammatory process. In this review, we discuss recent advances in our understanding of miRNAs and their connection to inflammatory responses. Additionally, we consider the link between perturbations in miRNA levels and the onset of human inflammatory diseases.
LIVER FUNCTION AS INFLUENCED BY ANESTHETICS AND NARCOTICS
Authors: G. H. Whipple, J. S. Speed
Journal: The Journal of Experimental Medicine (1915)

It has been established that specific liver poisons (chloroform, phosphorus) which cause histological changes in the liver cells, decrease the liver excretion of phenoltetrachlorphthalein. Also vascular disturbances (Eck fistula, passive congestion) with or without histological evidence may cause a fall in the output of phthalein through the liver. Sufficient evidence has been brought forward to show that the phenoltetrachlorphthalein excretion is a valuable index concerning the functional capacity of the liver. Ether anesthesia for a period of two hours usually causes a depression in the phthalein curve during the twenty-four hours following the anesthesia. Paraldehyde in doses sufficient to give anesthesia and stupor for a few hours will give adefinite fall in phthalein excretion. Chloral and urethane usually cause a decrease in phthalein output when given in considerable amounts. Alcohol causes a drop in the phthalein curve when given in large doses sufficient to cause stupor for a few hours. The drop in phenoltetrachlorphthalein excretion is demonstrated in the twenty-four hours following administration of the drug. A drop in the phthalein curve to two-thirds or one-half of normal indicates a definite liver injury and temporary impairment of function.
Chronic traumatic encephalopathy: clinical‐biomarker correlations and current concepts in pathogenesis
Authors: Sam Gandy, Milos D Ikonomovic, Effie Mitsis, Gregory Elder, Stephen T Ahlers, Jeffrey Barth, James R Stone, Steven T DeKosky
Journal: Molecular Neurodegeneration (2014)

Chronic traumatic encephalopathy (CTE) is a recently revived term used to describe a neurodegenerative process that occurs as a long term complication of repetitive mild traumatic brain injury (TBI). Corsellis provided one of the classic descriptions of CTE in boxers under the name "dementia pugilistica" (DP). Much recent attention has been drawn to the apparent association of CTE with contact sports (football, soccer, hockey) and with frequent battlefield exposure to blast waves generated by improvised explosive devices (IEDs). Recently, a promising serum biomarker has been identified by measurement of serum levels of the neuronal microtubule associated protein tau. New positron emission tomography (PET) ligands (e.g., [18 F] T807) that identify brain tauopathy have been successfully deployed for the in vitro and in vivo detection of presumptive tauopathy in the brains of subjects with clinically probable CTE. Major academic and lay publications on DP/CTE were reviewed beginning with the 1928 paper describing the initial use of the term CTE by Martland. The major current concepts in the neurological, psychiatric, neuropsychological, neuroimaging, and body fluid biomarker science of DP/CTE have been summarized. Newer achievements, such as serum tau and [18 F] T807 tauopathy imaging, are also introduced and their significance has been explained. Recent advances in the science of DP/CTE hold promise for elucidating a long sought accurate determination of the true prevalence of CTE. This information holds potentially important public health implications for estimating the risk of contact sports in inflicting permanent and/or progressive brain damage on children, adolescents, and adults.
Endothelial Progenitor Cells Stimulate Cerebrovascular Production of Prostacyclin By Paracrine Activation of Cyclooxygenase-2
Authors: Anantha Vijay R. Santhanam, Leslie A. Smith, Tongrong He, Karl A. Nath, Zvonimir S. Katusic
Journal: Circulation Research (2007)

In the present study we hypothesized that endothelial progenitor cells (EPCs) enhance production of vasoprotective substances in cerebral arteries. Isolated mononuclear cells from rabbit peripheral blood were cultured in endothelial growth medium (EGM-2) for 7 days to yield EPCs. Rabbit basilar arteries were exposed to autologous EPCs ( approximately 5x10(5) cells) in vitro or in vivo. Twenty-four hours after intracisternal delivery of autologous EPCs, basilar arteries were isolated and expression of vasoregulatory proteins, production of prostacyclin (PGI(2)), and cAMP were determined. Arteries transplanted with EPCs demonstrated increased protein expression of cyclooxygenase-2 and PGI(2) in adventitia, media, and endothelium. Furthermore, production of PGI(2) and arterial content of cAMP, second messenger for PGI(2), were significantly augmented after transplantation of EPCs. In contrast, production of thromboxane A(2) was significantly reduced, whereas production of prostaglandin E(2) remained unchanged. The increased production of PGI(2) and arterial content of cAMP were inhibited only by a selective cyclooxygenase-2 inhibitor, NS-398. In vitro or in vivo treatment of basilar artery with conditioned media from EPCs also caused increase in cyclooxygenase-2 and PGI(2) synthase protein expression associated with elevation of cAMP. Our results suggest that in cerebral arteries, paracrine effect of EPCs promotes vasoprotection by increasing PGI(2) production and intracellular concentration of cAMP. This effect appears to be mediated by activation of arachidonic acid metabolism via stimulation of cyclooxygenase-2/PGI(2) synthase pathway.
Effect of Hypotension due to Spinal Anesthesia on Coronary Blood Flow and Myocardial Metabolism in Man
Authors: DONALD B. HACKEL, S. M. SANCETTA, JEROME KLEINERMAN
Journal: Circulation (1956)

The induction of spinal anesthesia resulted in hypotension and decreased coronary blood flow and myocardial oxygen consumption. At the same time the myocardial extraction coefficient of oxygen was not increased, indicating myocardial oxygenation to be adequate for the lower work load. This does not imply that local ischemia might not occur in the presence of coronary artery sclerosis. The coronary arteriovenous differences of glucose, lactate and pyruvate were not changed during the period of hypotension.
Fertility preservation in female patients
Authors: M. Sonmezer
Journal: Human Reproduction Update (2004)

In the USA alone, >650 000 women will be afflicted by cancer in 2003, and 8% of these cases will be aged <40 years. Due to improvements in cancer therapy, cure rates of both adult and childhood cancers increased significantly over the past three decades. However, long‐term consequences of cancer therapy and impact on quality of life are now being recognized. One of the major sequelae of cytotoxic chemotherapy is gonadal failure. Cytotoxic chemotherapy and/or radiotherapy are not only used to treat malignant diseases, but also non‐malignant systemic conditions. Upon reviewing the extent and mechanism of gonadal damage due to chemo‐/radiotherapy, this article discusses indications and the wide range of methods of fertility preservation in a comprehensive manner. All current, emerging, experimental as well as controversial approaches are reviewed. A comprehensive algorithm to manage fertility preservation through an individualized approach is presented.
Deep resequencing of 131 Crohn's disease associated genes in pooled DNA confirmed three reported variants and identified eight novel variants
Authors: Sung Noh Hong, Changho Park, Soo Jung Park, Chang Kyun Lee, Byong Duk Ye, You Sun Kim, Seungbok Lee, Jeesoo Chae, Jong-Il Kim, Young-Ho Kim
Journal: Gut (2015)

<h3>Objective</h3> Genome wide association studies (GWAS) and meta-analyses for Crohn9s disease (CD) have not fully explained the heritability of CD, suggesting that additional loci are yet to be found and that the known loci may contain high effect rare risk variants that have thus far gone undetected by GWAS. While the cost of deep sequencing remains too high to analyse many samples, targeted sequencing of pooled DNA samples allows the efficient and cost effective capture of all variations in a target region. <h3>Design</h3> We performed pooled sequencing in 500 Korean CD cases and 1000 controls to evaluate the coding exon and 5′ and 3′ untranslated regions of 131 CD associated genes. The identified genetic variants were validated using genotyping in an independent set of 500 CD cases and 1000 controls. <h3>Results</h3> Pooled sequencing identified 30 common/low single nucleotide variants (SNVs) in 12 genes and 3 rare SNVs in 3 genes. Our results confirmed a significant association of CD with the following previously reported risk loci: <i>rs3810936</i> in <i>TNFSF15</i> (OR=1.83, p&lt;2.2×10<sup>−16</sup>), <i>rs76418789</i> in <i>IL23R</i> (OR=0.47, p=1.14×10<sup>−8</sup>) and <i>rs2241880</i> in <i>ATG16L1</i> (OR=1.30, p=5.28×10<sup>−6</sup>). In addition, novel loci were identified in <i>TNFSF8</i> (<i>rs3181374</i>, OR=1.53, p=1.03×10<sup>−14</sup>), <i>BTNL2</i> (<i>rs28362680</i>, OR=1.47, p=9.67×10<sup>−11</sup>), <i>HLA-DQA2</i> (<i>rs3208181</i>, OR=1.36, p=4.66×10<sup>−6</sup>), <i>STAT3</i> (<i>rs1053004</i>, OR=1.29, p=2.07×10<sup>−5</sup>), <i>NFKBIA</i> (<i>rs2273650</i>, OR=0.80, p=3.93×10<sup>−4</sup>), <i>NKX2-3</i> (<i>rs888208</i>, OR=0.82, p=6.37×10<sup>−4</sup>) and <i>DNAH12</i> (<i>rs4462937</i>, OR=1.13, p=3.17×10<sup>−2</sup>). A novel rare SNV, <i>rs200735402</i> in <i>CARD9</i>, was shown to have a protective effect (OR=0.09, p=5.28×10<sup>−5</sup>). <h3>Conclusions</h3> Our deep resequencing of 131 CD associated genes confirmed 3 reported risk loci and identified 8 novel risk loci for CD in Koreans, providing new insights into the genetic architecture of CD.
The arthritis of Constantine IX
Authors: D. E. Caughey
Journal: Annals of the Rheumatic Diseases (1974)

Early clinical descriptions of rheumatoid arthritis are rare, and it has been suggested (Boyle and Buchanan, 1971) that for this reason the paucity of evidence of the disease in early skeletons (Copeman, 1969; Grossman, 1966; Ruffer, 1918; Smith and Jones, 1910), the lack of reference to the disease in the Bible or in the works of Shakespeare (Ehrlich, 1967), and the failure to depict the deformities of the disease by the classical masters of the Dutch, French, Italian, and Spanish schools of painting, that this is a disease of comparatively recent times.The arthritis of the Emperor Constantine IX (c.980-1055), in keeping with theories at the time, was thought to be due to a disturbance of the basic humours.The account of the Emperor's illness was written by Michael Psellus in the Chronographia (Psellus, 1063), which forms an important source of the history of the Eastern Roman Empire from A.D. 976 to 1078.Michael Psellus was a Christian scholar, an adviser, friend, and tutor to successive Emperors, and he used his first-hand information of politics and the imperial court to write a memoir of his own times.His account vividly portrays the Byzantine way of life.He studied medical treatises, and is said to have practised the art of medicine.He was a careful observer of people and character studies are recorded with considerable psychological insight.Constantine Monomachus, who came to the throne because he was the third husband of the Empress Zoe, ruled between A.D. 1042 and 1055 (Figure, overleaf).Psellus described him as having an attractive person- ality, remarkable beauty, and considerable athletic prowess, and stated that he was an effective ruler and a good Christian, under whose rule the Empire pros- pered.After two paragraphs about the Emperor's appearance, Psellus devoted considerable space to the description of the Emperor's illness, which is here quoted in full.
Predicting the Outcome of Therapy for Pulmonary Tuberculosis
Authors: ROBERT S. WALLIS, MARK D. PERKINS, MANIJEH PHILLIPS, MOSES JOLOBA, ALICE NAMALE, JOHN L. JOHNSON, CHRISTOPHER C. WHALEN, LUCILEIA TEIXEIRA, BARBARA DEMCHUK, REYNALDO DIETZE, ROY D. MUGERWA, KATHLEEN EISENACH, JERROLD J. ELLNER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Patients vary considerably in their response to treatment of pulmonary tuberculosis. Although several studies have indicated that adverse outcomes are more likely in those patients with delayed sputum sterilization, few tools are available to identify those patients prospectively. In this study, multivariate models were developed to predict the response to therapy in a prospectively recruited cohort of 42 HIV-uninfected subjects with drug-sensitive tuberculosis. The cohort included 2 subjects whose initial response was followed by drug-sensitive relapse. The total duration of culture positivity was best predicted by a model that included sputum M. tuberculosis antigen 85 concentration on Day 14 of therapy, days-to-positive in BACTEC on Day 30, and the baseline radiographic extent of disease (R = 0.63). A model in which quantitative AFB microscopy replaced BACTEC also performed adequately (R = 0.58). Both models predicted delayed clearance of bacilli in both relapses ( > 85th percentile of all subjects) using information collected during the first month of therapy. Stratification of patients according to anticipated response to therapy may allow TB treatment to be individualized, potentially offering superior outcomes and greater efficiency in resource utilization, and aiding in the conduct of clinical trials.
<i>Reprimo</i> as a Potential Biomarker for Early Detection in Gastric Cancer
Authors: Carolina Bernal, Francisco Aguayo, Cynthia Villarroel, Macarena Vargas, Ignacio Díaz, Francisco J. Ossandon, Eudocia Santibáñez, Mariana Palma, Edmundo Aravena, Carlos Barrientos, Alejandro H. Corvalan
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Gastric cancer is a curable disease if diagnosed at early stage. However, most cases are diagnosed at advanced stage because of the lack of screening programs. Therefore, the identification of plasma biomarkers for early detection is necessary. Experimental Design: To search for these biomarkers, we evaluated the DNA methylation patterns of 24 genes by Methylation-specific PCR in primary tissues from 32 retrospectively collected gastric cancer cases (testing group). Correlation between methylation and gene expression was evaluated in the MKN-45 cell line after treatment with 5-aza-2′-deoxycytidine. The most frequently hypermethylated genes were next evaluated in primary tissues and plasma samples from 43 prospectively collected gastric cancer cases as well as plasma samples from 31 asymptomatic age- and gender-matched controls (validation group). Results: In the testing group, 11 genes were hypermethylated in at least 50% of cases (APC, SHP1, E-cadherin, ER, Reprimo, SEMA3B, 3OST2, p14, p15, DAPK, and p16). Eight genes (BRCA1, p73, RARβ, hMLH1, RIZI, RUNX3, MGMT, and TIMP3) were statistically associated with a particular variant of gastric cancer, the signet-ring cell type (P = 0.03). Seven genes (APC, SHP1, E-cadherin, ER, Reprimo, SEMA3B, and 3OST2) were next evaluated in the validation group. We confirm the high frequency of methylation in primary tumors for all seven genes. However, only APC and Reprimo were frequently methylated in pair plasma samples. In asymptomatic controls, only Reprimo was infrequently methylated in comparison with plasma from gastric cancer cases (P &amp;lt; 0.001). Conclusion: Our results identified specific methylation profile associated to signet-ring cell-type histology and aberrant hypermethylation of Reprimo as a potential biomarker for early detection of gastric cancer.