tbuckley/cabot-search huggingface dataset:
Abstract LB-203: Structural variants shuffle chromatin to activate GFI1 family oncogenes in medulloblastoma
Authors: Catherine Lee, Paul A. Northcott, Thomas Zichner, Peter Lichter, Jan O. Korbel, Stefan M. Pfister, Robert J. Wechsler-Reya
Journal: Cancer Research (2014)

Abstract Medulloblastoma is a highly malignant pediatric brain tumor currently treated with a combination of surgery, radiation, and non-specific chemotherapy, posing a significant threat to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma and identified four distinct molecular subgroups. Group 3 and Group 4 subgroup medulloblastomas account for the majority of pediatric cases, yet, oncogenic drivers for these subtypes remain poorly understood. Here we report a series of prevalent, highly disparate genomic structural rearrangements, restricted to Groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto- oncogenes, GFI1 &amp; GFI1B. Diverse mechanisms of structural variation activate GFI1/GFI1B expression through relocation of their coding sequences to genomic regions of transcriptionally active chromatin. Moreover, Gfi1 and Gfi1b each cooperate with Myc, an important oncogene in Group 3 medulloblastomas, to drive tumor initiation in mice. These data reveal GFI1 and GFI1B as novel medulloblastoma oncogenes, warranting their prioritization for molecularly targeted therapy of a marked proportion of Group 3 and Group 4 patients. Citation Format: Catherine Lee, Paul A. Northcott, Thomas Zichner, Peter Lichter, Jan O. Korbel, Stefan M. Pfister, Robert J. Wechsler-Reya. Structural variants shuffle chromatin to activate GFI1 family oncogenes in medulloblastoma. [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 LB-203. doi:10.1158/1538-7445.AM2014-LB-203
Progesterone oral contraception and blood coagulation.
Authors: L. Poller, J. M. Thomson, A. Tabiowo, C. M. Priest
Journal: BMJ (1969)

BRITISH in average P.E.F.rates in the morning or in the evening.All patients who were symptomatically better had an increase in P.E.F., including the three patients who had a smaller F.E.V.1; the use of a peak flow meter is of considerable value in follow- ing the response to treatment in asthmatics over a period of days or weeks, and in this trial it provided useful confirmation of symptomatic benefit (Epstein et al., 1969).The degree of symptomatic improvement did not correlate with initial F.E.V.1 results.Moran et al. ( 1968) reported a greater improvement in the younger patients, but in our series the reverse obtained.In the nine patients there was a reduction in average values of F.R.C. and R.V. Woolcock and Read (1966) found a greater reduction in T.L.C. in many of their cases, whereas only one of our patients showed a fall of as much as 1 litre.The difference may be due to the fact that Woolcock and Read's patients were studied during and after severe status asthmaticus.We did not find any improvement in exercise capacity in those who were symptomatically better despite an increase in ventilatory capacity as judged by F.E.V.1 and specific conduc- tance of airways.It would seem that ventilation did not limit exercise capacity in our subjects, though it would be expected to do so with a greater degree of airway obstruction.The reduction in pulse rate is unexplained.Altounyan (1964) showed that during attacks of asthma associated with allergy there is a poor response to inhaled atropine methylnitrate compared with isoprenaline sulphate, but that treatment with corticosteroids increases the atropine re- sponse.Patients with non-allergic airway obstruction usually have a high atropine response.In the present study the six
Graves Disease With Midline Ectopic and Bifid Pyramidal Lobes on Pertechnetate Thyroid Scintigraphy
Authors: Ajit Shinto, Abhijit Bandopadhyay, Job Selvakumar
Journal: Clinical Nuclear Medicine (2008)

Thyroid ectopia may present in isolation as the only functioning gland or may coexist along with a normal pretracheal thyroid. It is usually an asymptomatic mass and tends to increase in size under stress, when hormone demands increase, as in puberty, pregnancy, and stress. A pyramidal lobe is visualized when there is significant stimulation to the thyroid, is usually unilateral, and can arise from either lobe or isthmus, extending superiorly. We present a case of a patient with Graves disease, demonstrating an ectopic midline inferior nodule and bilateral pyramidal lobes on a pertechnetate thyroid scan. A 31-year-old male patient presented with a recent history of progressively increasing tremors, weight loss, tiredness, and increased sweating of 5-months duration. He had no history of thyroid complaints or contributory medical, surgical, and family history. On general physical examination, he had tachycardia with a pulse rate of 108/minute, fine tremors of the extremities, mild thyromegaly, and increased palmar sweating. His thyroid function tests were T3: 7.8 ng/mL (normal range 0.8–1.8 ng/mL), T4: 24.9 μg/dL (normal range 4.5–12.5 μg/dL), and TSH: 002 μIU/mL (normal range 0.5–9 μIU/mL). Tc 99m pertechnetate imaging was performed, which demonstrated diffuse, homogenous increased tracer uptake in bilateral thyroid lobes, bifid pyramidal lobes, and suppressed salivary gland uptake. In addition, there was a midline focus of intense tracer uptake inferior and separate from the thyroid margin, demonstrating increased vascularity on the flow images. USG Doppler was performed, which demonstrated increased vascularity in the nodule, supplied by the inferior thyroid artery and the echo texture similar to the rest of the thyroid tissue. Repeat pertechnetate scan done 3 months later demonstrated similar scan findings with a mild increase in the thyroid uptake (23%-33%). He was treated with 10 mCi of I-131 and is presently on follow-up and is asymptomatic.
Young people should be included as partners
Authors: A. McNulty
Journal: BMJ (2000)

EDITOR—The position of young people(between the ages of 13 and 18) as partners is not discussed in the BMJ issue of 18 September “Embracing patient partnership.” Dixon—Woods et al's article on partnerships with children begins with a reference to a 15 year old woman but focuses on important issues relevant to professionals working with children.1

Young people are, in political, …
Metabolic Changes Associated with Mitral Valvuloplasty
Authors: G. M. WILSON, I. S. EDELMAN, L. BROOKS, J. A. MYRDEN, D. E. HARKEN, F. D. MOORE
Journal: Circulation (1954)

Patients with chronic congestive heart failure operated upon for the surgical correction of mitral stenosis have been observed repeatedly to have low plasma sodium concentrations and elevated plasma potassium concentrations after operation. This study was primarily directed at an understanding of these abnormalities. The authors have shown that the preoperative patient has a characteristic disorder of body composition noteworthy for a high total body water, a high total body sodium, a low total exchangeable potassium and a low plasma sodium concentration. The effects of surgery on this abnormal body composition, and the therapeutic implications are discussed.
Plunging Parotid Tumour
Authors: D. H. Patey
Journal: BMJ (1963)

MEDICALJOURNAL 30 months of the trial.Among the 13,200 tuberculin- negative participants who were not vaccinated, there were 64 cases of tuberculosis, a rate of 4.85 per 1,000.Among the 14,100 tuberculin-negative participants who were given B.C.G. vaccine, there were 13 cases of tuber- culosis, a rate of 0.92 per 1,000.If a ruler is placed across the nomogram from 27,300 on the left-hand scale to 5.77 on the right-hand scale, it cuts the centre scale at the value 1.3 on the 5% side, and 1.7 on the 1 % side.Since even the latter is exceeded by the difference in rates of 3.93, the difference is significant at the 1 % level.This nomogram is most accurate when the two samples are of the same size-that is, m=n.It is reasonably satisfactory up to a difference in size of 3 to 1.
Seven doctors accused of over-prescribing heroin
Authors: Owen Dyer
Journal: BMJ (2004)

Seven drug addiction specialists were accused by the General Medical Council this week of excessive prescribing of heroin and other drugs, and inadequate surveillance of patients, in what will be the biggest disciplinary case in the history of the GMC.

The seven doctors worked at the Stapleford Centre, one of Britain's biggest private addiction clinics, with branches in Belgravia, London, and Stapleford Tawney, Essex. More than half of the GMC's charges relate to the founder of the Stapleford Centre, Dr Colin Brewer. The other six doctors, three of whom still …
Europe and nutrition.
Authors: A. MacNair
Journal: BMJ (1992)

s retrospective audit of acute gastrointestinal bleeding in a district general hospital highlights one of the main obstructions to audit and attempts to improve outcome-namely, the medical record.' Drawing any satisfactory conclusion from medical audit is difficult when 44% (46/104) of the case notes are unavailable.This is not an isolated problem.2Patients' care is also handicapped when notes are unavailable in outpatient departments or on the wards.Until this problem is resolved we will have to rely on prospective audits with data collection independent of case notes.Good, accessible medical records are the foundation for medical audit, clinical care, coding, resource management, and so on.They are fundamental to the service, and improvements are urgently needed.
Cytotoxic T lymphocyte response to hepatitis C virus-derived peptides containing the HLA A2.1 binding motif.
Authors: A Cerny, J G McHutchison, C Pasquinelli, M E Brown, M A Brothers, B Grabscheid, P Fowler, M Houghton, F V Chisari
Journal: Journal of Clinical Investigation (1995)

The HLA class I-restricted cytotoxic T lymphocyte (CTL) response is a major defense mechanism in viral infections. It has been suggested that the CTL response may contribute to viral clearance and liver cell injury during hepatitis C virus (HCV) infection. To test this hypothesis requires an understanding of the characteristics of HCV-specific cytotoxic effector cells and identification of the target antigens to which they respond. To begin this process we stimulated peripheral blood mononuclear cells (PBMC) from a group of HLA-A2 positive patients with chronic hepatitis C with a panel of 130 HCV-derived peptides containing the HLA-A2 binding motif. Effector cells were tested for their capacity to lyse HLA-A2-matched target cells that were either sensitized with peptide or infected with a vaccinia virus construct containing HCV sequences. Using this approach we have identified nine immunogenic peptides in HCV, three of which are derived from the putative core protein, three from the nonstructural (NS) 3 domain, two from NS4 and one from NS5. Selected responses were shown to be HLA-A2 restricted, mediated by CD8+ T cells and to recognize endogenously synthesized viral antigen. Unexpectedly, peptide-specific CTL responses could also be induced in sero-negative individuals, suggesting in vitro activation of naive CTL precursors. The precursor frequency of peptide-specific CTL was 10 to 100-fold higher in infected patients compared to uninfected controls, and the responses were greatly diminished by removal of CD45 RO+ (memory) T cells. Further quantitative studies are clearly required to establish whether a correlation exists between the HCV-specific CTL response and the clinical course of this disease. Definition of the molecular targets of the human CTL response to HCV creates this opportunity, and may also contribute to the development of a T cell-based HCV vaccine.
Frozen Section Analysis of Esophageal Endoscopic Mucosal Resection Specimens in the Real-Time Management of Barrett’s Esophagus
Authors: Ganapathy A. Prasad, Kenneth K. Wang, Lori S. Lutzke, Jason T. Lewis, Schuyler O. Sanderson, Navtej S. Buttar, Louis M. Wong Kee Song, Lynn S. Borkenhagen, Lawrence J. Burgart
Journal: Clinical Gastroenterology and Hepatology (2006)
Myocardial Infarction and Atrial Arrhythmias
Authors: THOMAS N. JAMES
Journal: Circulation (1961)

In each of 11 necropsied patients with myocardial infarction and atrial arrhythmias, a coronary occlusion was found proximal to the origin of the sinus node artery and there was infarction of the sinus node. The multiple factors influencing the onset of atrial arrhythmias during acute myocardial infarction are discussed. Infarction of the sinus node is only one of these factors. Other important ones are ischemia of the AV node, vagal and vagomimetic reflexes, atrial distention, and circulating chronotropic substances. By combination of a knowledge of the anatomy and pathology of the human coronary arteries with the observation of atrial arrhythmias during acute myocardial infarction, an accurate diagnosis of the point of coronary occlusion can often be made.
Retrospective Evidence Favoring Use of Anticoagulants for Myocardial Infarctions
Authors: James Tonascia, Leon Gordis, Helen Schmerler
Journal: New England Journal of Medicine (1975)

During a state-wide retrospective study of myocardial infarction discharges from Maryland hospitals from July, 1966, through June, 1967, the relation of in-hospital case fatality rates to use of anticoagulants was examined in 1,156 patients. In patients who did not receive anticoagulants, the rate was 2.5 times that of those who did (p less than 0.0001). A large difference in case fatality rates between the anticoagulant and no-anticoagulant groups persisted when the data were analyzed by demographic and medical-care variables. When patients were classified according to clinical characteristics relating to prognosis, including arrhythmia, congestive heart failure and shock, the difference between the groups were also demonstrated. Although such a retrospective study cannot demonstrate conclusively the value of anticoagulant therapy, the data are sufficiently suggestive of a beneficial effect to warrant reopening the anticoagulant question.
Genetic polymorphisms in arginase I and II and childhood asthma and atopy
Authors: H LI, I ROMIEU, J SIENRAMONGE, M RAMIREZAGUILAR, B ESTELADELRIONAVARRO, E KISTNER, H GJESSING, I LARASANCHEZ, G CHIU, S LONDON
Journal: Journal of Allergy and Clinical Immunology (2005)
The Rac1-GEF Tiam1 Couples the NMDA Receptor to the Activity-Dependent Development of Dendritic Arbors and Spines
Authors: Kimberley F. Tolias, Jay B. Bikoff, Alain Burette, Suzanne Paradis, Dana Harrar, Sohail Tavazoie, Richard J. Weinberg, Michael E. Greenberg
Journal: Neuron (2005)
Trends in Drug-Resistant Tuberculosis in the United States, 1993-1996
Authors: Marisa Moore
Journal: JAMA (1997)

With the resurgence of tuberculosis (TB) disease in the late 1980s and early 1990s in the United States, multidrug-resistant (MDR) TB emerged as a serious challenge to TB control. In response, the Centers for Disease Control and Prevention in 1993 added drug susceptibility test results to the information collected for the national surveillance system to monitor trends in drug resistance.To determine the extent of drug-resistant tuberculosis (TB) in the United States.Descriptive analysis of TB surveillance data.Patients reported to the national TB surveillance system as confirmed TB cases with culture-positive disease from 1993 through 1996 by the 50 states, New York City, and the District of Columbia (DC).Percentage of case patients with culture-positive disease whose isolates are resistant to specific anti-TB drugs.Overall resistance to at least isoniazid was 8.4%; rifampin, 3.0%; both isoniazid and rifampin (ie, MDR TB), 2.2%; pyrazinamide, 3.0%; streptomycin, 6.2%; and ethambutol hydrochloride, 2.2%. Rates of resistance were significantly higher for case patients with a prior TB episode. Among those without prior TB, isoniazid resistance of 4% or more was found in 41 states, New York City, and DC. A total of 1457 MDR TB cases were reported from 42 states, New York City, and DC; however, 38% were reported from New York City. Rates of isoniazid and streptomycin resistance were higher for cases among foreign-born compared with US-born patients [corrected] but rates of rifampin resistance and MDR TB were similar. Among US-born patients, resistance to first-line drugs, particularly rifampin monoresistance, was significantly higher among those with human immunodeficiency virus (HIV) infection.Compared with recent US surveys in 1991 and 1992, isoniazid resistance has remained relatively stable. In addition, the percentage of MDR TB has decreased, although the national trend was significantly influenced by the marked decrease in New York City. Foreign-born and HIV-positive patients and those with prior TB have higher rates of resistance. The widespread extent of isoniazid resistance confirms the need for drug susceptibility testing to guide optimal treatment of patients with culture-positive disease.
Characterization of CD3+, CD4-, CD8- clones expressing the putative T cell receptor gamma gene product. Analysis of the activation pathways leading to interleukin 2 production and triggering of the lytic machinery.
Authors: S Ferrini, C Bottino, R Biassoni, A Poggi, R P Sekaly, L Moretta, A Moretta
Journal: The Journal of Experimental Medicine (1987)

Four clones were derived from human peripheral blood T lymphocytes from which CD4+ and CD8+ cells had been removed by treatment with specific mAbs and complement. All expressed the CD2+, 3+, 4-, 8-, T44- phenotype, and did not react with the WT31 mAb, which is specific for a framework determinant of the CD3-associated alpha/beta heterodimer which serves as receptor for antigen on most human T lymphocytes. Surface iodination followed by crosslinking with dithiobis-succinimidyl propionate (DSP) and immunoprecipitation with anti-CD3 mAbs indicated that, in all four clones, the CD3-associated molecules consisted of a major 45 kD band and a minor band of 43 kD. Northern blot analysis showed that mRNA for the gamma chain was expressed at high levels, whereas mRNA for the alpha chain was missing; beta chain mRNA was present in a defective form (1 kb instead of 1.3 kb). These data support the concept that these clones may express, in association with CD3, the molecular product of the T cell receptor gamma genes instead of the typical alpha/beta heterodimer. CD3+, WT31- clones lysed the NK-sensitive K562 target cells and produced IL-2 upon stimulation with PHA. In addition, they released IL-2 after triggering with soluble anti-CD3 mAbs or with an appropriate combination of anti-CD2 mAbs (in the presence of adherent cells). When CD3+, WT31- clones were incubated with an anti-CD3 producing hybridoma as triggering target, the latter was efficiently lysed. Target cell lysis also occurred when a suitable combination of anti-CD2 mAbs-producing hybridomas was used. Therefore, CD3+, WT31- cells appear to use two pathways of cell activation that function also in conventional CD3+, WT31+ T cells, but they lack a third putative pathway initiated by T44 surface molecules.
Simple heuristics: From one infinite regress to another?
Authors: Aidan Feeney
Journal: Behavioral and Brain Sciences (2000)

Gigerenzer, Todd, and the ABC Research Group argue that optimisation under constraints leads to an infinite regress due to decisions about how much information to consider when deciding. In certain cases, however, their fast and frugal heuristics lead instead to an endless series of decisions about how best to decide.
Abstract 345: The intratumoral Wnt2B expression affects tumor progression in malignant pleural mesotheliomas
Authors: Masashi Kobayashi, Cheng-long Huang, Ryo Miyahara, Makoto Sonobe, Toshi Menju, Ryutao Kikuchi, Masashi Ishikawa, Jiro Kitamura, Shotaro Iwakiri, Kazumi Itoi, Hiroshi Date
Journal: Cancer Research (2011)

Abstract Introduction: Malignant pleural mesotheliomas are aggressive tumors with a poor prognosis. It is considered to be important to identify the molecular targets for the treatment against malignant pleural mesotheliomas. We have recently found the Wnt1 expression to affect tumor progression in non-small cell lung cancers, through the induction of various Wnt-targets (Huang et al, Eur J Cancer 2008). Therefore, we performed a clinical study on the intratumoral expressions of the canonical Wnts, such as Wnt1 and Wnt2B, in relation to their targets, including c-Myc and survivin. Methods: Sixty-five cases with malignant pleural mesotheliomas were investigated. Immunohistochemical assays were performed to evaluate the intratumoral expressions of Wnt1, Wnt2B, c-Myc and survivin. In addition, the Ki-67 proliferation index was evaluated by immunohistochemistry, and the apoptotic index was evaluated by the TUNEL method. Results: The Ki-67 proliferation index was significantly higher in c-Myc-high tumors than in c-Myc-low tumors (P=0.008). In addition, the Ki-67 proliferation index was also significantly higher nuclear-survivin-high tumors than in nuclear-survivin-low tumors (P=0.004). Regarding the intratumoral expressions of canonical Wnts, 18 tumors (27.7%) were Wnt1-high tumors, and 36 tumors (55.4%) were Wnt2B-high tumors. The rate of Wnt2B-high tumors was significantly higher than the rate of Wnt1-high tumors (P=0.024). Regarding tumor histology, the Wnt2B expression was the significantly highest in epithelial type (P&amp;lt;0.001). On the other hand, there was no significant difference in the Wnt1 expression according to the tumor histology (P=0.163). Furthermore, the Wnt 2B expression significantly correlated with expressions of c-Myc and survivin (P&amp;lt;0.001 and P&amp;lt;0.001, respectively). The c-Myc expression was significantly higher in Wnt2B-high tumors than in Wnt2B-low tumors (P&amp;lt;0.001), and the survivin expression was also significantly higher in Wnt2B-high tumors than in Wnt2B-low tumors (P=0.007). In contrast, there was no significant difference in c-Myc or survivin expressions according to the Wnt1 expression (P=0.218 and P=0.688, respectively). Conclusions: The intratumoral Wnt2B expression affects tumor progression of malignant pleural mesothelioma through the induction of c-Myc and survivin. The Wnt2B could be a candidate of targets of the molecular therapy against malignant pleural mesotheliomas. 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 345. doi:10.1158/1538-7445.AM2011-345