tbuckley/cabot-search huggingface dataset:
Abstract 5251: ASCL1 and RET expression define a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation
Authors: Farhad Kosari, Cristiane M. Ida, Marie Christine Aubry, Lin Yang, Irina V. Kovtun, Janet L. Schaefer Klein, Sandra C. Tomaszek, Stephen J. Murphy, Ping Yang, Dennis Wigle, George Vasmatzis
Journal: Cancer Research (2014)

Abstract ASCL1 is an important regulatory transcription factor in pulmonary neuroendocrine cell development, but its value as a biomarker of neuroendocrine differentiation in lung adenocarcinoma (AD) and as a potential prognostic biomarker remains unclear. We examined ASCL1expression in lung cancer samples of varied histologic subtype, clinical outcome, and smoking status and compared to expression of traditional neuroendocrine markers. ASCL1 mRNA expression was found almost exclusively in smokers with AD, in contrast to non-smokers. ASCL1 protein expression by immunohistochemistry (IHC) correlated best with synaptophysin compared to chromogranin and CD56/NCAM. Analysis of a compendium of 367 microarray-based gene expression profiles in stage I lung adenocarcinomas identified significantly higher expression levels of the RET oncogene in ASCL1 positive tumors (ASCL1+) compared to ASCL1- tumors (q-value &amp;lt; 10 - 9). High levels of RET expression in ASCL1+ but not in ASCL1- tumors was associated with significantly shorter overall survival in stage 1 (p = 0.007) and in all AD (p = 0.037). RET protein expression by IHC had an association with overall survival in the context of ASCL1 expression. In silico gene set analysis and in vitro experiments by ASCL1 shRNA in AD cells with high endogenous expression of ASCL1 and RET implicated ASCL1 as a potential upstream regulator of the RET oncogene. Also, silencing ASCL1 in AD cells markedly reduced cell growth and motility. These results suggest that ASCL1 and RET expression define a clinically relevant subgroup of approximately 10% of AD characterized by neuroendocrine differentiation. Citation Format: Farhad Kosari, Cristiane M. Ida, Marie Christine Aubry, Lin Yang, Irina V. Kovtun, Janet L. Schaefer Klein, Sandra C. Tomaszek, Stephen J. Murphy, Ping Yang, Dennis Wigle, George Vasmatzis. ASCL1 and RET expression define a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation. [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 5251. doi:10.1158/1538-7445.AM2014-5251
In vivo regulation of the allergic response by the IL-4 receptor α chain immunoreceptor tyrosine-based inhibitory motif
Authors: Raffi Tachdjian, Shadi Al Khatib, Andreas Schwinglshackl, Hong Sook Kim, Andrew Chen, Julie Blasioli, Clinton Mathias, Hye Young Kim, Dale T. Umetsu, Hans C. Oettgen, Talal A. Chatila
Journal: Journal of Allergy and Clinical Immunology (2010)
BAD-Dependent Regulation of Fuel Metabolism and KATP Channel Activity Confers Resistance to Epileptic Seizures
Authors: Alfredo Giménez-Cassina, Juan Ramón Martínez-François, Jill K. Fisher, Benjamin Szlyk, Klaudia Polak, Jessica Wiwczar, Geoffrey R. Tanner, Andrew Lutas, Gary Yellen, Nika N. Danial
Journal: Neuron (2012)
Lack of HLA class I antigen expression by melanoma cells SK-MEL-33 caused by a reading frameshift in beta 2-microglobulin messenger RNA.
Authors: Z Wang, Y Cao, A P Albino, R A Zeff, A Houghton, S Ferrone
Journal: Journal of Clinical Investigation (1993)

The lack of HLA class I antigen expression by the melanoma cell line SK-MEL-33 is caused by a unique lesion in beta 2-microglobulin (beta 2-mu). Sequencing of beta 2-mu mRNA detected a guanosine deletion at position 323 in codon 76 that causes a frameshift with a subsequent introduction of a stop codon at a position 54 base upstream of the normal position of the stop codon in the message. The loss of 18 amino acids and the change of 6 amino acids, including a cysteine at position 80 in the carboxy terminus of beta 2-mu, are likely to cause marked changes in the structure of the polypeptide. The latter may account for the inability of beta 2-mu to associate with HLA class I heavy chains and for its lack of reactivity with the anti-beta 2-mu mAb tested. HLA class I antigen expression on SK-MEL-33 cells was reconstituted after transfection with a wild-type B2m gene, therefore indicating that the abnormality of endogenous B2m gene is the only mechanism underlying lack of HLA class I antigen expression by SK-MEL-33 cells. The guanosine deletion in B2m gene was detected also in the melanoma tissue from which SK-MEL-33 cells had originated. Therefore, the molecular lesion identified in the SK-MEL-33 melanoma cell line is not caused by a mutation acquired during growth in vitro but is likely to reflect a somatic mutation during tumor progression.
Abnormal Cardiac Adrenergic Nerve Function in Patients With Syndrome X Detected By [ <sup>123</sup> I]Metaiodobenzylguanidine Myocardial Scintigraphy
Authors: Gaetano Antonio Lanza, Alessandro Giordano, Christian Pristipino, Maria Lucia Calcagni, Guido Meduri, Carlo Trani, Rodolfo Franceschini, Filippo Crea, Luigi Troncone, Attilio Maseri
Journal: Circulation (1997)

Previous studies have suggested that an abnormal cardiac adrenergic tone may have a pathophysiological role in syndrome X (effort angina, positive exercise testing, angiographically normal coronary arteries).To evaluate cardiac adrenergic nerve function, we performed [123I]metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 12 patients with syndrome X and 10 control subjects. Cardiac MIBG uptake was assessed by the heart/mediastinum (H/M) ratio and by an MIBG uptake defect score (higher values=lower uptake). In syndrome X patients, we also correlated MIBG scintigraphic findings with stress myocardial perfusion as assessed by 201Tl scintigraphy. An inferior MIBG defect was observed in only 1 control subject, whereas 9 patients (P<.01) showed MIBG defects. The heart was totally or almost totally invisible on MIBG images in 5 patients, and predominantly regional defects were observed in 4. The H/M ratio was lower (1.70+/-0.6 versus 2.2+/-0.3, P=.03) and MIBG uptake defect score higher (35+/-31 versus 4+/-2, P=.003) in syndrome X patients. Reversible stress thallium perfusion defects were found in 62% of patients with MIBG defects but in no patient with normal MIBG uptake. MIBG defects persisted unchanged in 7 patients at a 5+/-3-month follow-up study.In this study, obvious defects in global and/or regional cardiac MIBG uptake, indicating an abnormal cardiac adrenergic nerve function, were detected in 75% of patients with syndrome X. These findings strongly support the cardiac origin of chest pain in syndrome X, although the mechanisms and the pathophysiological meaning of the abnormal cardiac MIBG uptake in these patients deserve further investigation.
Author's reply to review of <i>Bioethics and Armed Conflict</i>
Authors: Michael L Gross
Journal: BMJ (2006)

As Nathanson says in her review of my book,1 I argue that the use of “moderate physical pressure” might be defensible in some cases. “Defensible” is the right word. The acts may be excused but are not justified. However, I don't defend interrogational torture with any great enthusiasm but simply admit that there might be some rare case where perpetrators might mount …
Community based retrospective study of sex in infant mortality in India
Authors: R Khanna
Journal: BMJ (2003)

To determine whether the imbalance in the sex ratio in India can be explained by less favourable treatment of girls in infancy.Analysis of results of verbal autopsy reports over a five year period.Community health project in urban India.Deaths from all causes in infants aged less than 1 year.The sex ratio at birth was 869 females per 1000 males. The mean infant mortality was 1.3 times higher in females than in males (72 v 55 per 1000). Diarrhoea was responsible for 22% of deaths overall, though twice as many girls died from diarrhoea. There were no significant differences in the numbers of deaths from causes such as birth asphyxia, septicaemia, prematurity, and congenital anomalies. In 10% of deaths there was no preceding illness and no satisfactory cause was found. Three out of every four such deaths were in girls.The excess number of unexplained deaths and deaths due to treatable conditions such as diarrhoeal disease in girls may be because girls are regarded and treated less favourably in India.
Carcinogenicity evaluations and ongoing studies: the IARC databases.
Authors: H Vainio, M Coleman, J Wilbourn
Journal: Environmental Health Perspectives (1991)

Many thousands of chemicals are produced industrially and many more occur naturally. Information on the toxicology of these chemicals is often minimal or absent. The International Agency for Research on Cancer (IARC) has published evaluations of the carcinogenic risk to humans of over 700 chemicals, groups of chemicals, and complex mixtures as a regular series of monographs. A database has been created containing summaries of all the relevant epidemiological, animal carcinogenicity, and other relevant biological data for each chemical or mixture evaluated. Additional databases have been created for ongoing epidemiological studies of cancer in humans and for long-term carcinogenicity studies in rodents, as well as a database containing information on genotoxic and related effects of chemicals. Some of these databases have been published in print form. IARC now plans to publish them electronically, together with other databases, in the form of a CDROM (compact disk, read-only memory). The objective will be to make the entire IARC database of cancer information as widely available as possible in an integrated format conducive to efficient and combined exploitation of all the component databases.
The Essential Sequence Elements Required for RNAP II Carboxyl-terminal Domain Function in Yeast and Their Evolutionary Conservation
Authors: P. Liu, A. L. Greenleaf, J. W. Stiller
Journal: Molecular Biology and Evolution (2008)

The carboxyl-terminal domain (CTD) of eukaryotic RNA polymerase II is the staging platform for numerous proteins involved in transcription initiation, mRNA processing, and general coordination of nuclear events. Concordant with these central roles in cellular metabolism, the consensus sequence, tandemly repeated structure, and core functions of the CTD are conserved across diverse eukaryotic lineages; however, in other eukaryotes, the CTD has been allowed to degenerate completely. Even in groups where the CTD is strongly conserved, genetic analyses and comparative genomic investigations show that a variety of individual substitutions and insertions are permissible. Therefore, the specific functional constraints reflected by the CTD's conservation across much of eukaryotic evolution have remained somewhat puzzling. Here we propose a hypothesis to explain that strong conservation in budding yeast, based on both comparative and experimental evidence. Through genetic complementation for CTD function, we identify 2 sequence elements contained within pairs of heptapeptides, "Y(1)-Y(8)" and "S(2)-S(5)-S(9)," which are required for all essential CTD functions in yeast. The dual requirements of these motifs can account for strong purifying selection on the canonical CTD heptapeptide. Further, in vitro analysis of GST-CTD fusion proteins as substrates for multiple CTD-directed kinases show reduced phosphorylation efficiencies with increased distance between functional units. This indicates that requirements of the RNAP II phosphorylation cycle are most likely responsible for the strong purifying selection on tandemly repeated CTD structure.
Inquiry into homicides by psychiatric patients: systematic audit should replace mandatory inquiries
Authors: N. Eastman
Journal: BMJ (1996)

Inquiries into homicides committed by psychiatric patients are currently mandatory under Department of Health guidance. They are often broadly defined in their terms of reference and almost always address not only the cause of the incident but also professional skill, practice, and culpability. Concurrent pursuit of both purposes is unlikely to maximise "learning from experience." Also, since inquiries can set their own thresholds for culpability, doctors can potentially be judged to a higher standard than would be required by the General Medical Council or negligence law. Lack of strict legal process increases the inherent potential unfairness to doctors. Investigation of cause and culpability should be separated and inquiries restricted to the former. There should also be a standing secretariat for inquiries to set terms of reference and to collate and distribute findings of inquiries. Widespread mandatory systematic audit of professional practice and service efficiency concerning risk assessment and management should largely replace costly ad hoc mandatory inquiries after homicides.
Monocyte recruitment in cryoglobulinemic membranoproliferative glomerulonephritis: A pathogenetic role for monocyte chemotactic peptide-1
Authors: Loreto Gesualdo, Giuseppe Grandaliano, Eelena Ranieri, Raffaella Monno, Vincenzo Montinaro, Carlo Manno, Francesco P. Schena
Journal: Kidney International (1997)
Prospectively defined indicators to improve the safety and quality of care for critically ill patients: a report from the Task Force on Safety and Quality of the European Society of Intensive Care Medicine (ESICM)
Authors: A. Rhodes, R. P. Moreno, E. Azoulay, M. Capuzzo, J. D. Chiche, J. Eddleston, R. Endacott, P. Ferdinande, H. Flaatten, B. Guidet, R. Kuhlen, C. León-Gil, M. C. Martin Delgado, P. G. Metnitz, M. Soares, C. L. Sprung, J. F. Timsit, A. Valentin
Journal: Intensive Care Medicine (2012)
Prenatal influences and prenatal diagnosis.
Authors: R W Smithells, B D Speidel
Journal: BMJ (1971)

Perinatal mortality has fallen dramatically since the turn of the century and is still falling.The present rate of 23 per 1,000 births is accounted for largely by babies of low birth weight, those with major congenital anomalies, and those subject, d to severe hypoxia.Haemolytic disease and infections are responsible for a diminishing number of perinatal deaths.
Entero-Vioform in Travelers' Diarrhea
Authors: Martin S. Wolfe
Journal: JAMA (1972)

<h3>To the Editor.—</h3> In a LETTER to the Editor ofThe Journalfor Nov 16, 1957, Kean criticized the advocacy by four consultants (in a query and minor note inThe Journalfor May 25, 1957) of the use of iodochlorhydroxyquin (Entero-Vioform) and similar preparations for the prophylactic treatment of amebiasis. He stated that evidence to show that iodochlorhydroxyquin is effective in prevention of amebiasis was inadequate and he also suggested potential dangers in using drugs containing iodine as prophylactics. Five years later an EDITORIAL on travelers' diarrhea inThe Journal(<b>180</b>:402, 1962) stated that "Entero-Vioform has been used so widely and so long that the lack of scientific evidence for its efficacy has been forgotten." During this 14-year period, no convincing evidence has been put forth that iodochlorhydroxyquin is a useful prophylactic for travelers' diarrhea. Richards, of CIBA Laboratories in England, studying the prophylactic use of iodochlorhydroxyquin as
Prognostic Significance of <i>p53</i> Mutation and p53 Overexpression in Advanced Epithelial Ovarian Cancer: A Gynecologic Oncology Group Study
Authors: Laura Havrilesky, Kathleen M. Darcy, Hasnah Hamdan, Roger L. Priore, Jorge Leon, Jeffrey Bell, Andrew Berchuck
Journal: Journal of Clinical Oncology (2003)

Purpose: The prognostic significance of p53 mutations and overexpression in advanced epithelial ovarian cancers was examined in primary tumors from 125 patients participating in a Gynecologic Oncology Group randomized phase III treatment protocol. Patients and Methods: Mutational analysis of p53 was performed in RNA or genomic DNA extracted from frozen tumor. An immunohistochemistry assay was used to detect p53 overexpression in fixed tumor. Results: There were 81 patients (74%) with a single mutation, three patients (3%) with two mutations, and 25 patients (23%) lacking a mutation in exons 2 to 11 of p53. Although most mutations occurred within exons 5 to 8, mutations outside this region were observed in 11% of patients. A mutation in exons 2 to 11 of p53 was associated with a short-term improvement in overall survival and progression-free survival. Adjusted Cox modeling demonstrated a 70% reduction in risk of death (P = .014) and a 60% reduction in risk of disease progression (P = .014) for women with such mutations. However, these striking risk reductions increased over time (P &lt; .02) and eventually disappeared with longer follow-up. Overexpression of p53 was observed in 55 patients (100%) with only missense mutation(s), seven patients (32%) with truncation mutations, and eight patients (40%) lacking a mutation in exons 2 to 11. Overexpression of p53 was associated with tumor grade but not with patient outcome. Conclusion: Alterations in p53 are a common event in advanced epithelial ovarian cancer. A mutation in p53, but not overexpression of p53, is associated with a short-term survival benefit. Additional studies are required to define the roles that p53 plays in regulating therapeutic responsiveness and patient outcome.
Hospital Services — Encouraging Private Medicine — Generous Pay Award
Authors: John Lister
Journal: New England Journal of Medicine (1980)

WHEN Mr. Enoch Powell was Minister of Health, he carried out a comprehensive survey of all the hospitals in England and Wales and outlined a pattern for the future development of the hospital service.1 He pointed out that in 1948 the National Health Service (NHS) inherited about 2800 hospitals with 500,000 beds from a large number of voluntary bodies and local authorities. Many of these hospitals were in obsolete buildings; about 45 per cent had been built before 1891 and 21 per cent before 1861. Furthermore, their geographic distribution had developed as a result of historical causes, and many were . . .
My Three Valves
Authors: John T. Harrington
Journal: New England Journal of Medicine (1993)

“Whatever you say, you say nothing.” When I was asked to write an editorial on my personal experiences with heart-valve surgery, that pithy phrase of Seamus Heaney, succinctly expressing the Catholic code of silent speech in Northern Ireland, came to mind. That code had leapt from Belfast to the town where I grew up, a working-class community of hills, mills, and churches in Massachusetts. The code was strong enough so that during the time I possessed my native aortic valve (which I will here term the era of valve I), few people other than my family knew of my illness. . . .
Prevalence, viral replication efficiency and antiviral drug susceptibility of rtQ215 polymerase mutations within the hepatitis B virus genome
Authors: Samad Amini-Bavil-Olyaee, Ulf Herbers, Seyed Reza Mohebbi, Farzaneh Sabahi, Mohammad Reza Zali, Tom Luedde, Christian Trautwein, Frank Tacke
Journal: Journal of Hepatology (2009)
Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction. Final results from the Primary Angioplasty Registry.
Authors: B R Brodie, C L Grines, R Ivanhoe, W Knopf, G Taylor, J O'Keefe, R A Weintraub, L G Berdan, J E Tcheng, L H Woodlief
Journal: Circulation (1994)

BACKGROUND After direct angioplasty in the setting of acute myocardial infarction, patients were followed clinically and angiographically for 6 months at six experienced centers to evaluate outcomes. METHODS AND RESULTS Of 258 patients with 6-month follow-up after surviving initial hospitalization, 5 (2%) died, 8 (3%) had nonfatal infarctions, 56 (22%) had chest pain, of whom 25 (10%) required hospitalization, and 42 (16%) patients needed repeat angioplasty. Of 203 eligible patients, 154 (76%) had angiographic follow-up. The infarct-related artery remained patent (defined as TIMI 2 or 3 flow) in 87%, while 13% developed reocclusion (TIMI 0 or 1 flow) by 6 months after discharge. Patients with reocclusion were more likely to have adverse events, including 35% with clinically evident reinfarction and 59% requiring repeat angioplasty. The median ejection fraction improvement from acute to follow-up study was 6%, with no improvement in patients with a reoccluded infarct-related artery and an 8% improvement in patients with a patent infarct-related artery. CONCLUSIONS The positive clinical outcomes recorded immediately after direct angioplasty persisted through 6 months of follow-up. Although the incidence of clinical end points was equivalent to or lower than thrombolytic therapy trials, restenosis is a substantial problem. These findings provide evidence beyond the initial hospitalization that direct angioplasty is a reasonable choice for the treatment of acute myocardial infarction.
Non‐invasive predictors of survival in cardiac amyloidosis
Authors: Arnt V. Kristen, Jolanta B. Perz, Stefan O. Schonland, Ute Hegenbart, Philipp A. Schnabel, Joern H. Kristen, Hartmut Goldschmidt, Hugo A. Katus, Thomas J. Dengler
Journal: European Journal of Heart Failure (2007)
Prolylcarboxypeptidase promotes angiogenesis and vascular repair
Authors: Gregory N. Adams, Evi X. Stavrou, Chao Fang, Alona Merkulova, M. Amer Alaiti, Kohsuke Nakajima, Toshifumi Morooka, Sergei Merkulov, Gretchen A. LaRusch, Daniel I Simon, Mukesh K. Jain, Alvin H. Schmaier
Journal: Blood (2013)
Maternal nutrition in early and late pregnancy in relation to placental and fetal growth
Authors: K Godfrey, S Robinson, D. Barker, C Osmond, V Cox
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To assess how nutrient intakes of mothers in early and late pregnancy influence placental and fetal growth. <b>Design</b>: Prospective observational study. <b>Setting</b>: Princess Anne Maternity Hospital, Southampton. <b>Subjects</b>: 538 mothers who delivered at term. <b>Main outcome measures</b>: Placental and birth weights adjusted for the infant9s sex and duration of gestation. <b>Results</b>: Mothers who had high carbohydrate intakes in early pregnancy had babies with lower placental and birth weights. Low maternal intakes of dairy and meat protein in late pregnancy were also associated with lower placental and birth weights. Placental weight fell by 49 g (95% confidence interval 16 g to 81 g; P=0.002) for each log g increase in intake of carbohydrate in early pregnancy and by 1.4 g (0.4 g to 2.4 g; P=0.005) for each g decrease in intake of dairy protein in late pregnancy. Birth weight fell by 165 g (49 g to 282 g; P=0.005) for each log g increase in carbohydrate intake in early pregnancy and by 3.1 g (0.3 g to 6.0 g; P=0.03) for each g decrease in meat protein intake in late pregnancy. These associations were independent of the mother9s height and body mass index and of strong relations between the mother9s birth weight and the placental and birth weights of her offspring. <b>Conclusion</b>: These findings suggest that a high carbohydrate intake in early pregnancy suppresses placental growth, especially if combined with a low dairy protein intake in late pregnancy. Such an effect could have long term consequences for the offspring9s risk of cardiovascular disease.
Daily or three times a week interferon alfa-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C
Authors: Victor de Lédinghen, Pascale Trimoulet, Maria Winnock, Juliette Foucher, Marc Bourlière, Hervé Desmorat, Valérie Canva, Dominique Capron, Stéphane Lévy, François Mion, Paul-Régis Mannant, Geneviève Chêne, Hervé Fleury, Patrice Couzigou, Pierre-Henri Bernard
Journal: Journal of Hepatology (2002)