tbuckley/cabot-search huggingface dataset:
Downregulated miR329 and miR410 Promote the Proliferation and Invasion of Oral Squamous Cell Carcinoma by Targeting Wnt-7b
Authors: Shine-Gwo Shiah, Jenn-Ren Hsiao, Wei-Min Chang, Ya-Wen Chen, Ying-Tai Jin, Tung-Yiu Wong, Jehn-Shyun Huang, Sen-Tien Tsai, Yuan-Ming Hsu, Sung-Tau Chou, Yi-Chen Yen, Shih Sheng Jiang, Yi-Shing Shieh, I-Shou Chang, Michael Hsiao, Jang-Yang Chang
Journal: Cancer Research (2014)

Abstract microRNA (miRNA) dysregulation contributes widely to human cancer but has not been fully assessed in oral cancers. In this study, we conducted a global microarray analysis of miRNA expression in 40 pairs of betel quid–associated oral squamous cell carcinoma (OSCC) specimens and their matched nontumorous epithelial counterparts. Eighty-four miRNAs were differentially expressed in the OSCC specimens compared with the matched tissue. Among these downregulated miRNAs, 19 miRNAs were found and mapped to the chromosome 14q32.2 miRNA cluster region, which resides within a parentally imprinted region designated as Dlk-Dio3 and known to be important in development and growth. Bioinformatic analysis predicted two miRNAs from the cluster region, miR329 and miR410, which could potentially target Wnt-7b, an activator of the Wnt–β-catenin pathway, thereby attenuating the Wnt–β-catenin signaling pathway in OSCC. Stable ectopic expression of Wnt-7b in OSCC cells overexpressing miR329 or miR410 restored proliferation and invasion capabilities abolished by these miRNA. Combining a demethylation agent and a histone deacetylase inhibitor was sufficient to reexpress miR329, miR410, and Meg3, consistent with epigenetic regulation of these miRNA in human OSCC. Specifically, arecoline, a major betel nut alkaloid, reduced miR329, miR410, and Meg3 gene expression. Overall, our results provide novel molecular insights into how betel quid contributes to oral carcinogenesis through epigenetic silencing of tumor-suppressor miRNA that targets Wnt–β-catenin signaling. Cancer Res; 74(24); 7560–72. ©2014 AACR.
NHS doctors can work in independent treatment centres, UK health minister announces
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

NHS doctors will be allowed to work in independent treatment centres once they have fulfilled their contractual obligations to the NHS. Patricia Hewitt, the UK secretary of state for health, made the announcement at the annual conference of the BMA in Manchester this week.

In addition, doctors in specialties without shortages who want to work full time for independent treatment centres will be allowed to leave the NHS and take up their new post without having to wait six months. Until now, this …
The Benefits of Endoscopy in Upper Gastrointestinal Bleeding
Authors: P. Rutgeerts, G. Vantrappen
Journal: Endoscopy (1986)

Management of the patient with upper gastrointestinal bleeding is a continuing challenge to the gastroenterologist and the surgeon. Endoscopy early in the course of bleeding benefits the patient only when diagnostic accuracy is combined with definitive hemostatic therapy. Effective methods are now available for endoscopic hemostasis of bleeding ulcers and bleeding varices. However, an improvement in the outcome of gastrointestinal bleeding is not easily achieved, since age and the incidence of severe underlying disease in patients with upper G.I. hemorrhage have been steadily increasing over the years.
Does the locus on chromosome 11 implicated in susceptibility to HLA-DR4 dependent type I diabetes mellitus also affect susceptibility to rheumatoid arthritis?
Authors: K.D Pile, B.P Wordsworth, J.I Bell
Journal: Annals of the Rheumatic Diseases (1992)

There is a polygenic component to rheumatoid arthritis (RA) in addition to the known association with HLA-DR4. It has previously been shown in another autoimmune disease (type I diabetes mellitus) that a gene on chromosome 11p can act with HLA-DR4 to enhance susceptibility (relative risk 5-6). It is therefore possible that this locus may also affect the development of RA. Genotype frequencies at this locus, defined by a dimorphic Fok 1 restriction site, were compared in 139 healthy controls and 213 patients with classical/definite RA. In contrast with diabetes there was no increase in genotypes lacking the Fok 1 site, either in the rheumatoid group overall (125/211 compared with 86/139 controls) or in the DR4 positive rheumatoid group (76/140 compared with controls). These results indicate that the interaction between DR4 and a locus on chromosome 11p is not common to all DR4 associated autoimmune diseases.
NEW UNIVERSAL DEFINITION OF MYOCARDIAL INFARCTION FOR RISK STRATIFICATION AND REVASCULARIZATION DECISION MAKING: IS IT ENOUGH?
Authors: Rita Calé, Jorge Ferreira, Carlos Aguiar, Nuno Santos, Pedro Carmo, João Figueira, Luis Raposo, Pedro Gonçalves, José A. Silva
Journal: Journal of the American College of Cardiology (2010)
Plasma β-MSH levels in acne vulgaris
Authors: A.J. THODY, S.K. GOOLAMALI, J.L. BURTON, N.A. PLUMMER, S. SHUSTER
Journal: British Journal of Dermatology (2006)

Plasma β‐MSH levels and sebum excretion rates (SER) were measured in thirty male and twelve female patients with acne vulgaris. The mean SER in both male and female patients was significantly increased as compared to normal control levels. Plasma β‐MSH levels were normal in male and female patients with acne and showed no correlation with the SER. The SER that occurs in acne cannot therefore be explained by an increased secretion of β‐MSH.
Multiple myeloma presenting high fever and high serum levels of lactic dehydrogenase, CRP, and interleukin-6
Authors: Hirokazu Murakami, Satoru Takada, Nahoko Hatsumi, Akihiko Yokohama, Takayuki Saitoh, Hideki Uchiumi, Tadashi Maehara, Takafumi Matsushima, Norifumi Tsukamoto, Kimio Morita, Jun'ichi Tamura, Morio Sawamura, Masamitsu Karasawa
Journal: American Journal of Hematology (2000)

Two myeloma patients presented high fever with no signs or data indicating infection at diagnosis or relapse. Both patients had plasmablastic myeloma, and serum levels of lactic dehydrogenase (LDH) and CRP were extremely high. Plasmablastic morphology, high LDH, and CRP were recognized as poor prognostic factors, indicating a fulminant phase of multiple myeloma. Interleukin-6 (IL-6) was only high in measured cytokines. We proposed that IL-6 caused high fever and induced the fulminant phase in these 2 cases. Am. J. Hematol. 64:76–77, 2000. © 2000 Wiley-Liss, Inc.
Effect of sulfonylureas on triglyceride metabolism in the rat liver: possible role of the lysosomes in hepatic lipolysis.
Authors: L J Debeer, J Thomas, G Mannaerts, P J DeSchepper
Journal: Journal of Clinical Investigation (1977)

It has been suggested previously that chlorpropamide and other hypoglycemic sulfonylureas interfere with hepatic triglyceride breakdown. Since ketogenesis from endogenous hepatic lipid stores is a measure of hepatic triglyceride hydrolysis, ketogenesis derived from endogenous lipids as well as ketogenesis derived from exogenously added isotopic oleate was determined in isolated hepatocytes from fasted rats in an attempt to identify the nature of the direct effects of sulfonylureas on hepatic lipid metabolism. Ketogenesis from endogenous lipids was inhibited by 1 mM chlorpropamide, while ketone production from exogenous oleate did not change. The effect of chlorpropamide on hepatic triglyceride metabolism was further studied in the isolated perfused liver of normal rats in the presence of a continuous [3H]oleate infusion and in isolated liver cells incubated in the presence of [3H]oleate. In liver perfusion experiments, 1 mM chlorpropamide enhanced the incorporation of tritium into triglycerides (but not other lipid classes) and increased both liver triglyceride content and triglyceride secretion. Using isolated cells similar effects could be demonstrated at 0.5 mM chlorpropamide. Chlorpropamide, tolbutamide, and carbutamide, all of which inhibited endogenous ketogenesis in isolated liver cells, also inhibited lysosomal triglyceride lipase activity in rat liver homogenates. The drugs were not inhibitory towards alkaline lipase activity. Demethylglycodiazin (2-benzolsulfonamid--5-(beta-hydroxyethoxy)-pyrimidin), which did not inhibit endogenous ketogenesis in isolated liver cells, did not affect lysosomal lipase activity. The lysosomotropic drug chloroquine was markedly antiketogenic when tested in liver cells. The reduction in endogenous ketogenesis, the enhanced accumulation of liver triglycerides, and the stimulation of hepatic triglyceride output by chlorpropamide are ascribed to an interference of the drug with hepatic triglyceride breakdown. The present results also suggest that the lysosomes play a significant role in hepatic lipolysis.
A COMPARISON OF HUMAN ANTISERA TO PURIFIED DIPHTHERIA TOXOID WITH ANTISERA TO OTHER PURIFIED ANTIGENS BY QUANTITATIVE PRECIPITIN AND GEL DIFFUSION TECHNIQUES
Authors: Irving Finger, Elvin A. Kabat
Journal: The Journal of Experimental Medicine (1958)

The limits of sensitivity of three gel diffusion methods are compared and their utilization in the detection of small amounts of antibody to antigens present in traces in a preparation is illustrated with the diphtheria toxin-human antitoxin system. The Preer modification of the Oakley-Fulthorpe technique and the Oudin tube method were found more sensitive than the Ouchteriony plate method, and permitted the detection of as little as 3 microg. antibody N/ml. of serum. Antisera from eight Schick-negative individuals immunized with purified diphtheria toxoid have all been shown to contain, in addition to antitoxin, antibodies to substances present as impurities in the purified toxoid injected. The amounts of these antibodies in a serum and a partial characterization of their antigen-antibody curves have been determined through the combined use of quantitative precipitin and gel diffusion methods. Different amounts of antibody have been precipitated by toxin and toxoid from individual sera. Evidence is presented that this may have been due to slight differences in antigenic specificity. A serum, Hu, which had been held to contain no precipitating antibody, has now been shown, by the Preer and Oudin techniques, to contain at least 12 microg. of precipitating antibody N (per ml. serum) against an impurity in the toxoid preparation. This estimate has been confirmed by quantitative precipitin determinations. The presence of antibodies to impurities in all human antitoxins examined in the present work brings into question the assumption that human antitoxin as such has a skin-sensitizing capacity.
Rodent Phylogeny and a Timescale for the Evolution of Glires: Evidence from an Extensive Taxon Sampling Using Three Nuclear Genes
Authors: Dorothée Huchon, Ole Madsen, Mark J. J. B. Sibbald, Kai Ament, Michael J. Stanhope, François Catzeflis, Wilfried W. de Jong, Emmanuel J. P. Douzery
Journal: Molecular Biology and Evolution (2002)

Rodentia is the largest order of placental mammals, with approximately 2,050 species divided into 28 families. It is also one of the most controversial with respect to its monophyly, relationships between families, and divergence dates. Here, we have analyzed and compared the performance of three nuclear genes (von Willebrand Factor, interphotoreceptor retinoid-binding protein, and Alpha 2B adrenergic receptor) for a large taxonomic sampling, covering the whole rodent and placental diversity. The phylogenetic results significantly support rodent monophyly, the association of Rodentia with Lagomorpha (the Glires clade), and a Glires + Euarchonta (Primates, Dermoptera, and Scandentia) clade. The resolution of relationships among rodents is also greatly improved. The currently recognized families are divided here into seven well-defined clades (Anomaluromorpha, Castoridae, Ctenohystrica, Geomyoidea, Gliridae, Myodonta, and Sciuroidea) that can be grouped into three major clades: Ctenohystrica, Gliridae + Sciuroidea, and a mouse-related clade (Anomaluromorpha, Castoridae + Geomyoidea, and Myodonta). Molecular datings based on these three genes suggest that the rodent radiation took place at the transition between Paleocene and Eocene. The divergence between rodents and lagomorphs is placed just at the K-T boundary and the first splits among placentals in the Late Cretaceous. Our results thus tend to reconcile molecular and morphological-paleontological insights.
Adjuvant Chemotherapy in Colorectal Cancer: Mournful, Hopeful Perpetual Motion Machine Heads to Dim Light at End of Tunnel-Reply
Authors: Michael O'Connell
Journal: JAMA (1989)

<h3>In Reply. —</h3> We agree entirely with Dr Clouse that adjuvant therapy trials in colon cancer that have been completed and reported in the medical literature have failed to document unequivocally a significant benefit. Observation following curative resection remains appropriate standard medical practice. However, we disagree emphatically with his statement that "we do not need yet another trial of adjuvant chemotherapy for colorectal cancer." Modest but nevertheless significant advances in the therapy of advanced colorectal cancer have been achieved by the biochemical modulation of 5-fluorouracil by leucovorin,<sup>1-3</sup>and this combination certainly deserves testing in the adjuvant setting. This currently is being carried out as an intergroup trial under the auspices of the National Cancer Institute, which has designated this a "high priority" study of national importance. Furthermore, preliminary data using levamisole alone or in combination with 5-fluorouracil<sup>4</sup>provide some evidence that biologic response modifiers might be effective in
Cystic fibrosis transmembrane regulator gene carrier status is a risk factor for young onset pancreatic adenocarcinoma
Authors: R McWilliams, W E Highsmith, K G Rabe, M de Andrade, L A Tordsen, L M Holtegaard, G M Petersen
Journal: Gut (2005)

Plexiform neurofibroma mimicking a pancreatic cystic tumourPancreatic neurogenic tumours are extremely rare. 1
Independent impact of gout on the risk of diabetes mellitus among women and men: a population-based, BMI-matched cohort study
Authors: Young Hee Rho, Na Lu, Christine E Peloquin, Ada Man, Yanyan Zhu, Yuqing Zhang, Hyon K Choi
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> Evidence on the potential independent impact of gout on the risk of diabetes is limited to a single study of men with a high cardiovascular risk profile. Our objective was to examine this relation in the general population, particularly among women. <h3>Methods</h3> We conducted a sex-stratified matched cohort study using data from The Health Improvement Network (THIN), an electronic medical records database representative of the UK general population. Up to five non-gout individuals were matched to each case of incident gout by year of birth, year of enrolment and body mass index (BMI). Multivariate HRs for incident diabetes were calculated after additionally adjusting for smoking, alcohol consumption, physician visits, comorbidities and medication use. <h3>Results</h3> Among 35 339 gout patients (72.4% men, mean age of 62.7 years), the incidence rates of diabetes in women and men were 10.1 and 9.5 cases per 1000 person-years, respectively, whereas the corresponding rates were 5.6 and 7.2 cases per 1000 person-years among 137 056 non-gout subjects. The BMI-matched univariate and multivariate HRs of diabetes were higher among women compared with those among men (1.71; 95% CI 1.51 to 1.93 vs 1.22; 95% CI 1.13 to 1.31) and (1.48; 95% CI 1.29 to 1.68 vs 1.15; 95% CI 1.06 to 1.24), respectively (p values for interaction &lt;0.001). This sex difference persisted across age-specific subgroups. <h3>Conclusions</h3> This general population-based study suggests that gout may be independently associated with an increased risk of diabetes and that the magnitude of association is significantly larger in women than in men.
A Ventilation Unit for Special Intensive Care of Patients With Respiratory Failure
Authors: Theodore H. Noehren
Journal: JAMA (1968)

Experience from an annual census of 859 patients in an intensive care unit has lead to the development of a special ventilation care facility. The average length of stay for patients with respiratory failure in the general unit has been 9.7 days, as compared with 2.2 and 4.6 days for individuals with other surgical and medical problems, respectively. The complicated multiple-system responses to ventilatory failure, particularly of the chronic chest disease patient, demand specialized equipment and experience at all levels of intensive care which are best served by a unit devoted exclusively to this type problem. It is anticipated that this will become as much a pattern of operation in all first-rate hospitals as have the general intensive care and coronary care units.
A NEW COMBINATION CHART FOR THE EXAMINATION OF SCHOOL CHILDREN'S EYES AND EARS BY TEACHERS.
Authors: FRANK ALLPORT
Journal: JAMA (1898)

As an adjunct to my method for the systematic examination of school children's eyes by teachers, I have prepared a special compound test card, which I submit. It is based upon the standard types of Snellen, and is called "A Visual and Aural Chart for Schools." Roman numerals are on one side of each line and Arabic on the other. As, notwithstanding frequent instruction and printed directions, I am frequently asked by teachers, "which is the proper line to test by at twenty feet?" I have had printed under the twenty-foot line the following words: "This line should be seen by a normal eye at 20 (xx) feet," which would seem to make the matter perfectly plain. Under the last line on the card proper, is a half broken line, at which point the lower portion of the compound card should be severed from the upper portion. Just under this
Blood Diseases of Infancy and Childhood in the Tradition of Carl H. Smith
Authors: Derry Ridgway
Journal: JAMA (1995)

The extended title, "In the tradition of Carl H. Smith," is embossed for the first time on the cover of this venerable text. The founding author's name is thus restored to the spine, where it can be discovered by students, house officers, and others sent by senior pediatricians to "read about it in Smith's<i>Blood Diseases</i>." Library copies of the sixth edition, just five years old, are thoroughly worn, suggesting that pediatricians continue to find this text a valuable reference, with or without Dr Smith's name on the cover. According to the tradition of Carl Smith, the field of pediatric hematology is partitioned into red cells, white cells, and hemostasis. After a few preliminary topics, which could not be fitted into Dr Smith's compartments, the editors of the seventh edition hold to the traditional divisions. In the opening 50 pages, Denis Miller discusses hematologic ontogeny, fetal hematopoiesis, blood problems particular
Bell's Palsy
Authors: Donald H. Gilden
Journal: New England Journal of Medicine (2004)

A healthy 50-year-old man notices that his face is drooping on the right side. On examination, facial asymmetry is evident, and some saliva has accumulated on the right side of the patient's mouth. When the patient attempts to close his eyes, his right eye does not close, although it rolls upward, and he is unable to show his teeth or inflate his cheek on the right. How should the patient be evaluated? Does he need immediate treatment?
Abstract 3574: Studies of castrate resistant 22Rv1 cells identifies AR regulated interrelated networks of transcription factors, co-regulators, chromatin, and nuclear scaffolding proteins.
Authors: Maria Mudryj, Stephen J. Libertini, Alan P. Lombard
Journal: Cancer Research (2013)

Abstract Prostate cancer development, progression and acquisition of castrate resistance are reliant on the activity of the androgen receptor (AR), a transcription factor that governs the proliferation of prostate cancer cells. Multiple studies have focused on the principle components that are critical for cell cycle transversal and these studies have identified members of the E2F/RB family, c-Myc, cyclins and cyclin dependent kinase inhibitors as key proteins that are instrumental in prostate cell proliferation and development of castrate resistance. But the mechanism by which the AR dominates this process is unclear. To identify the link between the AR and cell cycle control we used 22Rv1 cells which are castrate resistant due to the expression of low molecular weight AR forms that are missing the ligand binding domain. However, a siRNA mediated decrease in AR expression induces a growth arrest confirming that proliferation is AR dependent. RNA-seq analysis of gene expression at castrate levels of androgen and following AR ablation identified transcripts that were AR dependent. This methodology reduced the number of AR regulated transcripts, by excluding transcripts regulated by super-physiological levels of androgens. The AR regulated transcripts included previously identified genes (PMEPA1, C1orf116, PCDH7, APP) including NFAT a gene shown to be regulated by a low molecular weight AR isoform. The analysis also revealed that interrelated networks of transcription factors and co-factors were AR transactivated or repressed. These included proteins such as the LBR, LMNB, TMPO and SATB1 that do not directly promote transcription, but rather link chromatin to the nuclear membrane or scaffolding, suggesting that the AR may modulate gene expression through epigenetics mechanisms. Network analysis showed connections between these proteins and cell cycle components including E2Fs and Myc where a number of the regulated transcripts are known E2F or Myc targets. In addition, this analysis identified a number of non-coding RNAs; some that have been previously described and some that have yet to be annotated. qPCR studies found that a number of the transcripts regulated in 22Rv1 cells are also AR regulated in LNCaP cells. Coupled with ChIP-seq data, the study characterizes the link between the AR and the cell cycle machinery and chromatin modulating proteins. Citation Format: Maria Mudryj, Stephen J. Libertini, Alan P. Lombard. Studies of castrate resistant 22Rv1 cells identifies AR regulated interrelated networks of transcription factors, co-regulators, chromatin, and nuclear scaffolding proteins. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3574. doi:10.1158/1538-7445.AM2013-3574
Abortion: how early, how late, and how legal?
Authors: V Tunkel
Journal: BMJ (1979)

Of all the sociomedical questions of our time, none is more frequently and hotly debated than abortion. Until now the debate has mostly been about the morality of abortion and whether the grounds for medical termination are too lax or too restrictive, either in theory or in practice. A lawyer who inter venes to ask  what do you mean by 'abortion' ? might be dismissed by all sides as quibbling or side tracking. Yet abortion in the legal sense remains a serious crime, one of several in this area. And the trouble with crimes?especially those as ancient as abortion?is that their definitions and profiles do not auto matically adjust to changing social or scientific developments. Doctors are quite familiar with the Abortion Act 1967; but that really tells us of only one circumstance in which the crime of abortion is not committed. Many doctors fail to see that Act in its setting, section 58, Offences against the Person Act 1861, and beside its ever-encroaching neighbour, the Infant Life (Preservation) Act 1929. Several recent happenings, affecting doctors, hospitals, and health authorities, suggest that it would be helpful to take a good look at the condition of the law at the two extremes of gestation, where the scope of the crime of abortion begins and ends ; and to look at the actual words of the law, which as often as not is paraphrased.