tbuckley/cabot-search huggingface dataset:
Abstract A21: MALAT-1 is essential for lung cancer metastasis in a novel human knockout model
Authors: Tony Gutschner, Moritz Eißmann, Monika Hämmerle, Marion Stentrup, Catherina Hildenbrandt, Matthias Groß, Martin Zörnig, Sven Diederichs
Journal: Cancer Research (2012)

Abstract The highly conserved long non-coding RNA MALAT-1 (Metastasis-Associated in Lung Adenocarcinoma Transcript 1) had been discovered as a prognostic marker associated with poor survival and development of distant metastasis in lung adenocarcinoma. Since then, it has been found to be deregulated in numerous tumor entities and has been linked to splicing. However, its functional relevance in tumor cells remains to be elucidated. Knockdown models for MALAT1 have been described but suffer from insufficient silencing efficiency of the highly abundant, nuclear non-coding RNA (ncRNA). In this project, we have developed a novel strategy to create ncRNA knockouts in human cancer cell lines. We have successfully used a synthetic Zinc Finger Nuclease engineered to target the 5′-region of MALAT1 to stably and biallelically integrate RNA-destabilizing elements into the genome of human lung cancer cells (A549). This approach resulted in a specific and more than 1000-fold silencing of MALAT1 in individual clones compared to a less than 5-fold silencing using siRNAs. Thus, this approach can be used to create functional knockouts of coding as well as non-coding genes also in human tumor cell lines allowing loss-of-function studies also of non-conserved ncRNAs in the future. Phenotypically, the MALAT1-Knockout cells (KO) greatly differ from their parental cell line and wildtype clones (WT): Next to morphological changes, the migration of the KO cells is largely impaired as shown in scratch assays. In xenograft assays after i.v. injection, the KO cells form significantly fewer and smaller lung metastases than their WT counterparts. Since no large difference was observed after subcutaneous injection of the WT and the KO cells, this indicates a specific, active and essential function of MALAT1 in metastasis. Exon microarrays of the WT and KO cell lines have revealed multiple migration- or metastasis-associated transcripts deregulated by loss of MALAT1 and hence potential target genes. These analyses also uncovered, that splicing is likely not the only functional mechanism of MALAT1 in the nucleus. Taken together, we have developed a novel, highly effective approach for the knockout of genes that can be used for non-coding as well as coding RNAs in human tumor cells as well as cells from other species. Knockout of MALAT1 in human lung cancer cells revealed its essential function in metastasis as well as genes directly and indirectly targeted by MALAT1. Citation Format: Tony Gutschner, Moritz Eißmann, Monika Hämmerle, Marion Stentrup, Catherina Hildenbrandt, Matthias Groß, Martin Zörnig, Sven Diederichs. MALAT-1 is essential for lung cancer metastasis in a novel human knockout model [abstract]. In: Proceedings of the AACR Special Conference on Noncoding RNAs and Cancer; 2012 Jan 8-11; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(2 Suppl):Abstract nr A21.
CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets
Authors: Michelle K. Gleason, Julie A. Ross, Erica D. Warlick, Troy C. Lund, Michael R. Verneris, Andres Wiernik, Stephen Spellman, Michael D. Haagenson, Alexander J. Lenvik, Mark R. Litzow, Pearlie K. Epling-Burnette, Bruce R. Blazar, Louis M. Weiner, Daniel J. Weisdorf, Daniel A. Vallera, Jeffrey S. Miller
Journal: Blood (2014)
Obama administration highlights health benefits of carbon plan
Authors: M. McCarthy
Journal: BMJ (2014)

In an apparent effort to make its plan to cut US power plant carbon emissions more relevant to the average person, the Obama administration has focused firstly on the plan’s purported health benefits and secondly on its effects on climate change.

For example, rather than giving his usual weekly televised address from the White House, President Barack Obama spoke about the new carbon plan from the Children’s National Medical Center in Washington, DC, where he had visited children with asthma and other medical conditions.

“Often, these illnesses are aggravated by air pollution—pollution from the same sources that release carbon and contribute to climate change,” Obama said in his address. “And for the sake of all our kids, we’ve got to do more to reduce it.”

Obama went on to give more detail about the new guidelines, which he said …
Progressive dysphagia, dysarthria, dystonia, and tremor
Authors: N Davendralingam, I Davagnanam, A Djamshidian, A Lees
Journal: BMJ (2010)

A 25 year old woman presented to our institution with increasing difficulty in swallowing, talking, and walking, which resulted in her being virtually mute, wheelchair bound, and perpetually drooling. She had presented to another institution two and a half years before with worsening episodes of headache and cramp in both feet. This had progressed to a generalised weakness of her entire body, in addition to impaired speech and problems with motor coordination.

Clinical examination showed cog wheel rigidity and a generalised jerky dystonic tremor, with occasional hemiballismic movement of the arms. The upper limb reflexes and power were normal. Bilateral wasting of the quadriceps muscles was apparent, with generalised brisk reflexes and severe spasticity of the lower limbs. Her speech was slurred but examination of the cranial nerve was otherwise unremarkable. Bilateral corneal discoloration was noted.

The patient’s full blood count, renal biochemical profile, and liver biochemical profile were largely normal, although alanine aminotransferase was slightly raised at 35 IU/l (normal range 10-35), as was alkaline phosphatase at 374 U/l (35-104). Magnetic resonance imaging (MRI) of the brain was performed at the time of presentation (fig 1)⇓.



Fig 1 Axial T2 weighted (A and B) and coronal fluid attenuation inversion recovery (FLAIR) (C) magnetic resonance imaging of the brain





### 1 What abnormalities are seen on the brain images?

#### Short answer

The brain images show increased T2 weighted signal in the pons, midbrain, thalami, and basal ganglia. Putaminal …
Changes in gastric mucosa after vagotomy and gastrojejunostomy for duodenal ulcer.
Authors: P C Watt, J M Sloan, T L Kennedy
Journal: BMJ (1983)

Gastric mucosa was studied histologically in 141 patients. Eighty two had undergone vagotomy and gastrojejunostomy between 15 and 25 years previously for duodenal ulcer, and 59 control patients had a long history (minimum 15 years) of duodenal ulcer treated medically. No carcinoma was found in either group. Two patients with severe dysplasia and 13 patients with moderate dysplasia were found in the study group, compared with none in the control group (p less than 0.01). Intestinal metaplasia was seen in 44 (53%) of the study group and 16 (27%) of the control group (p less than 0.01). Atrophy and gastritis were more severe (p less than 0.01 for atrophy; p = 0.05 for gastritis) in the study group. Gastric mucosal changes were more severe after surgical treatment for duodenal ulcer than after medical treatment, and possibly a high incidence of gastric carcinoma may occur 25 years after vagotomy and gastrojejunostomy.
Visualization of Soft Tissue by Technetium-99m MDP in Polymyositis Case Reports
Authors: NOBUAKI OTSUKA, MASAO FUKUNAGA, SHIMATO ONO, KIYOHISA NAGAI, KOICHI MORITA, TATSUSHI TOMOMITSU, SHINICHI YANAGIMOTO, KENJI MORIMOTO, AKIRA TERAO, RIKUSHI MORITA
Journal: Clinical Nuclear Medicine (1988)

Two patients with polymyositis showed abnormal muscular uptake of Tc-99m-methylene diphosphonate (MOP) during routine bone imaging. Imaging with Tc-99m MDP is a uselul tool in monitoring the activity of the diseased muscle.
Five-Year Follow-Up of the Medicine, Angioplasty, or Surgery Study (MASS) : A Prospective, Randomized Trial of Medical Therapy, Balloon Angioplasty, or Bypass Surgery for Single Proximal Left Anterior Descending Coronary Artery Stenosis
Authors: W. A. Hueb, P. R. Soares, S. Almeida de Oliveira, S. Arie, R. H. A. Cardoso, D. B. Wajsbrot, L. A. M. Cesar, A. D. Jatene, J. A. F. Ramires
Journal: Circulation (1999)

Although coronary angioplasty and myocardial bypass surgery are routinely used, there is no conclusive evidence that these interventional methods offer greater benefit than medical therapy alone. This study is intended to evaluate, in a prospective, randomized, and comparative analysis, the benefit of the 3 current therapeutic strategies for patients with stable angina and single proximal left anterior descending coronary artery stenosis.In a single institution, 214 patients with stable angina, normal ventricular function, and severe proximal stenosis (>80%) on the left anterior descending artery were selected for the study. After random assignment, 70 patients were referred to surgical treatment, 72 to angioplasty, and 72 to medical treatment. The primary end points were the occurrence of acute myocardial infarction or death and presence of refractory angina. After a 5-year follow-up, these combined events were reported in only 6 patients referred to surgery as compared with 29 patients treated with angioplasty and 17 patients who only received medical treatment (P=0.001). However, no differences were noted in relation to the occurrence of cardiac-related death in the 3 treatment groups (P=0. 622). No patient assigned to surgery needed repeat operation, whereas 8 patients assigned to angioplasty and 8 patients assigned to medical treatment required surgical bypass after the initial random assignment. Surgery and angioplasty reduced anginal symptoms and stress-induced ischemia considerably. However, all 3 treatments effectively improved limiting angina.Bypass surgery for single-vessel coronary artery disease is associated with a lower incidence of medium-term and long-term events as well as fewer anginal symptoms than that found in the patients who underwent angioplasty or medical therapy. In this study, coronary angioplasty was only superior to medical strategies in relation to the anginal status. However, the 3 treatment regimens yielded a similar incidence of acute myocardial infarction and death. Such information should be useful when choosing the best therapeutic option for similar patients.
Points from Letters: Post-herpetic Pruritus
Authors: K. Liddell
Journal: BMJ (1975)

autonomy, heads of departments may be able, for example, to finance replacement equipment from money saved during periods when there are unfilled posts in a department.It might also make more sense to use cheaper analytical methods and reagents.Such. a policy might enable a measure of Mr. Crossman's redeployment of money to take place without crippling the existing service.However, only departmental man- agers can make their services more efficient.It cannot be properly or safely done by remote administrators making arbitrary and swingeing cuts based on ill-conceived ideas or inadequate information.If financial stringency is to be the com- pulsory order of the day it should be applied impartially throughout the N.H.S.Let us renmember that few ordinary doctors have ever been convinced of the need for the new enlarged administration required to run the Health Service reorganization.In some areas of activity the region now wields more power than it did before 1 April 1974, and the area is left like a castrato tenor warbling in- effectually between the baritone soloist at the district and the bass obligato at the region.The new management system has yet to prove both its own effectiveness and cost- benefit to the community.Perhaps some of these less than essential gentlemen should recll Cromwell's famous assessment of the Rump
Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey
Authors: Y. Bombard, G. Veenstra, J. M Friedman, S. Creighton, L. Currie, J. S Paulsen, J. L Bottorff, M. R Hayden
Journal: BMJ (2009)

<b>Objective</b> To assess the nature and prevalence of genetic discrimination experienced by people at risk for Huntington's disease who had undergone genetic testing or remained untested. <b>Design</b> Cross sectional, self reported survey. <b>Setting</b> Seven genetics and movement disorders clinics servicing rural and urban communities in Canada. <b>Participants</b> 233 genetically tested and untested asymptomatic people at risk for Huntington's disease (response rate 80%): 167 underwent testing (83 had the Huntington's disease mutation, 84 did not) and 66 chose not to be tested. <b>Main outcome measures</b> Self reported experiences of genetic discrimination and related psychological distress based on family history or genetic test results. <b>Results</b> Discrimination was reported by 93 respondents (39.9%). Reported experiences occurred most often in insurance (29.2%), family (15.5%), and social (12.4%) settings. There were few reports of discrimination in employment (6.9%), health care (8.6%), or public sector settings (3.9%). Although respondents who were aware that they carried the Huntington's disease mutation reported the highest levels of discrimination, participation in genetic testing was not associated with increased levels of genetic discrimination. Family history of Huntington's disease, rather than the result of genetic testing, was the main reason given for experiences of genetic discrimination. Psychological distress was associated with genetic discrimination (P&lt;0.001). <b>Conclusions</b> Genetic discrimination was commonly reported by people at risk for Huntington's disease and was a source of psychological distress. Family history, and not genetic testing, was the major reason for genetic discrimination.
The Market Structure of Residency Training
Authors: Michael E. Whitcomb, Jeffrey Caswell
Journal: New England Journal of Medicine (1986)

During the past year, three major bills dealing with the organization and financing of graduate medical education were introduced in the U.S. Congress. The desire to control Medicare expenditures for medical education was the primary stimulus for this legislative activity; however, manpower issues, particularly the maldistribution of specialty physicians, were considered early in the discussions of how best to effect cost savings and ultimately dominated much of the debate about specific legislative proposals.Despite general agreement that it was desirable to increase the percentage of graduating medical students who entered and completed training in a primary care specialty, there was . . .
Changes in ratio during orthotopic liver transplantation (OLT)
Authors: J. Moreno, J.S. Ortega, F. Acoata, A.R. Ribó, A. Olivares, R.F. Contreras, P. Parrilla, F.S. Bueno, P. Ramirez, J. Rodriquez
Journal: Journal of Hepatology (1991)
480 GAS6 IS CONSTITUTIVELY PRODUCED BY HUMAN STELLATE CELLS AND ITS PLASMA CONCENTRATION REFLECTS CIRRHOSIS PROGRESSION
Authors: C. Marconi, R. Minisini, P. Sainaghi, L. Franzosi, F. Alciato, C. Fabris, P. Toniutto, G. Avanzi, M. Pirisi
Journal: Journal of Hepatology (2008)
Abstract 1641: Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer
Authors: Nelson S. Yee, Stephen G. Chun, Weiqiang Zhou, I-Chau Liang
Journal: Cancer Research (2011)

Abstract We aim to test the hypothesis that histone deacetylases (HDACs) and RNA polymerase III (Polr3) cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. This hypothesis is based on the observations that HDACs and POLR3 play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Using chemical inhibitors of HDACs and POLR3, we examined the effect on exocrine pancreas during morphogenesis, and then translated the developmental findings to human pancreatic adenocarcinoma cultured cells. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A) and an inhibitor of Polr3 (ML-60218) synergistically prohibited expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the clinical HDAC inhibitor suberoyl-anilide hydroxamic acid (SAHA) and ML-60218 produced enhanced suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive induction of a pro-apoptotic regulator and the cyclin-dependent kinase inhibitors. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators in zebrafish can be translated into a potential therapeutic approach in human cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1641. doi:10.1158/1538-7445.AM2011-1641
A REVIEW OF A GROUP OF PROFESSIONAL DONORS
Authors: HERBERT Z. GIFFIN
Journal: JAMA (1923)

Statements in the literature concerning the subsequent condition of patients who have acted as donors are not accompanied by statistical data. Minot and Lee,<sup>1</sup>in their article on the transfusion of blood, state that several transfusions of 500 c.c. may be given by a single donor, at intervals of one week or more, without apparent disturbance. After 500 c.c. has been given, the donor will feel well within a few hours. A loss of 1,000 c.c. may cause lassitude for two or three days. The blood volume in normal persons is made up rapidly from the fluid reserve of the body, and the number of erythrocytes returns to normal within a few weeks. The inadvisability of using students and nurses as donors has been discussed in the<i>Lancet</i><sup>2</sup>and in the<i>Guy's Hospital Gazette</i>.<sup>3</sup>It is rather surprising that, aside from these discussions, nothing has appeared in
Danish group reanalyses miscarriage in NSAID users
Authors: G. L. Nielsen
Journal: BMJ (2004)

EDITOR—Li et al reported that use of non-steroidal anti-inflammatory drugs (NSAIDs) in the first half of pregnancy is associated with an 80% increased risk of miscarriage, which is in accordance with our previous results.1 2

We have since accessed a recent update of our dataset covering 1998-2002, including gestational age, which was not …
TULAREMIA IN DOGS
Authors: L. F. Ey
Journal: JAMA (1941)

From the literature on the subject of tularemia we realize that some questions remain undetermined in regard to the susceptibility of certain animals and birds to this disease. For example, it is evident that sufficient evidence has not been produced to place the common dog in the group of susceptible or naturally immune animals. Obviously it can be understood that the material required to study the susceptibility of dogs under natural conditions is not always readily accessible. Consequently investigators interested in this phase of the problem have limited their observations to experimental studies. From the few experimental studies we are given the impression that the dog is only mildly susceptible to tularemia, and other opinions indicate that this animal possesses a natural immunity. In this communication we are prepared to show that dogs can contract tularemia under favorable natural conditions and that a resultant high agglutination titer for Bacterium tularense
What Is the Oslerian Tradition?
Authors: Charles S. Bryan
Journal: Annals of Internal Medicine (1994)

Discussants of internal medicine often invoke but seldom define "the Oslerian tradition," which has many meanings. No definition provides clear insight into the issues now relevant to American internal medicine, primarily because, as William Osler knew, the field itself shows definitional ambivalence. The tradition might be best understood as a virtuous approach to medicine and to life as taught and modeled by Osler. If we understand his philosophy and methods, we will be better prepared to use and pass on (tradere, "to deliver") something of greater value: the ability to make wise choices that are in society's best interest.
A<i>SOX9</i>Duplication and Familial 46,XX Developmental Testicular Disorder
Authors: James J. Cox, Lionel Willatt, Tessa Homfray, C. Geoffrey Woods
Journal: New England Journal of Medicine (2011)

ulin (a putative megalin ligand) was also detected in this patient, but immunohistochemical analyses revealed no apparent change in its uptake (Fig. S4E and S4F in the Supplementary Appendix), which suggested β 2 -microblobin is also a shared ligand.Consequently, we tested the binding capacity of α 1 -microglobulin to cubilin (with the use of surface-plasmon-resonance analyses, as described in the Supplementary Appendix and shown in Fig. S3B) and found that α 1 -microglobulin is also a cubilin ligand.Studies in rodents have shown that both cubilin and amnionless are essential to normal embryonic development.However, no lethal phenotype or malformations were observed in the dogs deficient in amnionless in the above-mentioned model.Since our patient has no additional apparent developmental abnormalities or physical disabilities, it appears that cubilin is not essential for human embryonic development.Furthermore, the functional immunohistochemical analyses of specimens from this patient's kidney indicate that cubilin and amnionless also have an interdependent relationship in humans.
Critical role of EBNA1-specific CD4+ T cells in the control of mouse Burkitt lymphoma in vivo
Authors: Tihui Fu, Kui Shin Voo, Rong-Fu Wang
Journal: Journal of Clinical Investigation (2004)

CD4+ T cells play important roles in orchestrating host immune responses against cancer and infectious diseases. Although EBV-encoded nuclear antigen 1–specific (EBNA1-specific) CD4+ T cells have been implicated in controlling the growth of EBV-associated tumors such as Burkitt lymphoma (BL) in vitro, direct evidence for their in vivo function remains elusive due to the lack of an appropriate experimental BL model. Here, we describe the development of a mouse EBNA1-expressing BL tumor model and the identification of 2 novel MHC H-2I-Ab–restricted T cell epitopes derived from EBNA1. Using our murine BL tumor model and the relevant peptides, we show that vaccination of mice with EBNA1 peptide–loaded DCs can elicit CD4+ T cell responses. These EBNA1-specific CD4+ T cells recognized peptide-pulsed targets as well as EBNA1-expressing tumor cells and were necessary and sufficient for suppressing tumor growth in vivo. By contrast, EBNA1 peptide–reactive CD8+ T cells failed to recognize tumor cells and did not contribute to protective immunity. These studies represent what we believe to be the first demonstration that EBNA1-specific CD4+ T cells can suppress tumor growth in vivo, which suggests that CD4+ T cells play an important role in generating protective immunity against EBV-associated cancer.