tbuckley/cabot-search huggingface dataset:
Abstract B30: EBV LMP2A bypasses p53 inactivation in a MYC model of lymphomagenesis
Authors: Kathryn T. Bieging, Alexandra C. Amick, Richard Longnecker
Journal: Cancer Research (2009)

Abstract Although Epstein-Barr virus (EBV) is linked to Burkitt's lymphoma (BL), the role of the virus in lymphomagenesis is unclear. LMP2A, encoded by EBV, is detected in BL biopsies and has pro-survival functions. We generated mice expressing MYC and LMP2A in B cells. Pretumor LMP2A/λ-MYC mice have significantly enlarged spleen size. In addition, LMP2A/λ-MYC mice show greatly accelerated tumor onset compared to λ-MYC mice. Inactivation of the p53 pathway and failure to induce the pro-apoptotic BH3-only protein, BIM are two major paths to tumor formation in MYC tumor models. Similar to previous work, we found p53 mutations in λ-MYC tumors, however we detected no p53 mutations in the rapidly arising LMP2A/λ-MYC tumors. We further demonstrate that the p53 pathway is functionally intact in LMP2A/λ-MYC tumors, which show increased levels of PUMA and sensitivity to p53 activation by Nutlin. We also show that BIM is induced in LMP2A/λ-MYC tumor cells. Despite the presence of p53 mutations in EBV+ human BL, our mouse model can be used to understand BL development in humans. We believe that LMP2A is important early in lymphomagenesis. The pro-survival function of LMP2A leads to an initial expansion of cells that have acquired a MYC translocation. This expansion is shown in our mouse model by enlarged spleens in pre-tumor mice. In humans, early expansion of cells increases the probability that a p53 mutation will occur in a cell with translocated MYC. Once the p53 mutation occurs, weak immune surveillance may select against high levels of LMP2A, consistent with low levels of LMP2A transcripts found in tumor biopsies. We have identified a novel mechanism that permits lymphomagenesis in the presence of an intact p53 pathway. This work also uncovers a contribution of Epstein-Barr virus (EBV) to molecular events that have documented importance in BL pathogenesis, and may underlie the poorly understood link between EBV and BL. Citation Information: Cancer Res 2009;69(23 Suppl):B30.
Flow-Function Mismatch in Unstable Angina Pectoris Demonstrated by Gated Tl-201 SPECT
Authors: K Fukuchi, Y Yasumura, K Hayashida, Y Ishida
Journal: Clinical Nuclear Medicine (2001)

FUKUCHI, KAZUKI M.D.*; YASUMURA, YOSHIO M.D.†; HAYASHIDA, KOHEI M.D.†; ISHIDA, YOSHIO M.D.* Author Information
Lower Incidence of Postpartum Thyrotoxicosis in Women With Graves Disease Treated by Radioiodine Therapy Than by Subtotal Thyroidectomy or With Antithyroid Drugs
Authors: Ai Yoshihara, Jaeduk Yoshimura Noh, Natsuko Watanabe, Kenji Iwaku, Sakiko Kobayashi, Miho Suzuki, Hidemi Ohye, Masako Matsumoto, Yo Kunii, Koji Mukasa, Koichi Ito
Journal: Clinical Nuclear Medicine (2014)

The incidence of postpartum thyrotoxicosis (PT) in Graves disease (GD) patients treated with antithyroid drugs (ATDs) is higher than in the general population, but the incidence of PT among GD patients who had been treated with radioiodine (RI) or by subtotal thyroidectomy before their pregnancy is not well known.We reviewed the cases of women with GD who had become pregnant, and we selected the 188 women who had undergone RI therapy before the pregnancy and the 148 women who had undergone subtotal thyroidectomy for GD before the pregnancy as the subjects of this study. The ATD subjects were 107 women with GD who had become pregnant after being treated with ATDs alone before their pregnancy and were in remission before and throughout the pregnancy.The overall incidence of PT was 2.1% (4/188) in the RI group, 23.6% (35/148) in the subtotal thyroidectomy group, and 55.1% (59/107) in the ATD group. There were no cases of permanent thyrotoxicosis in the RI group.The incidence of PT among women with GD who have undergone RI therapy before their pregnancy was significantly low compared to thyroidectomy group and ATD group. This finding is interesting because the incidence of PT in the RI group was lower than subtotal thyroidectomy group even though thyroid volume had been greatly reduced by thyroidectomy. RI treatment is recommended in the choice of treatment for childbearing-age women as regards the risk of postpartum recurrence.
Rational Therapy for Secondary Amenorrhea
Authors: William P. Given, Ralph W. Gause, R. Gordon Douglas
Journal: New England Journal of Medicine (1950)

THE practitioner of medicine is often confronted with relatively young women who complain of scanty or absent menstruation and infertility. Their desire is primarily to become pregnant and secondarily to have normal menstrual periods. Yet, in the past, physicians have placed much emphasis on merely inducing menstrual bleeding, and too little attention has been directed to the problem of ovulation in these patients. It is the purpose of this communication to evaluate 50 patients treated for secondary amenorrhea in an attempt to draw certain conclusions regarding the production of ovulation and subsequent pregnancy.A very important contribution to our understanding . . .
S40 TNFα Reduces BMPR-II Expression But Enhances BMP6 Signalling Via ActR-IIa in Pulmonary Arterial Smooth Muscle Cells
Authors: LA Hurst, AA Rana, NW Morrell, PD Upton
Journal: Thorax (2012)

Mutations in the bone morphogenetic protein type-II receptor (BMPR-II) underlie ∼70% of heritable pulmonary arterial hypertension (PAH) cases. However, the low penetrance in mutation carriers implies a ‘second hit’ is required for disease onset. A possible trigger is inflammation. Circulating tumour necrosis factor alpha (TNFα) is raised in PAH patients and TNFα can alter smooth muscle cell proliferation. Thus, we examined the effect of TNFα on BMP signalling. Human pulmonary arterial smooth muscle cells (PASMCs) were derived from patients with BMPR-II mutations and from disease-free controls. Quantitative polymerase chain reaction (qPCR) and western blotting revealed that 24 hours of TNFα stimulation reduced the expression of BMP2 and BMPR-II but increased BMP6 expression. TNFa reduced BMP2-mediated signalling, as expected. In contrast, BMP6 treatment in the presence of TNFα increased smad1/5 activation and upregulated ID1 expression, implying that BMP6 can signal independently of BMPR-II Furthermore, BMPR-II mutant PASMCs proliferated in response to BMP6 and TNFα. Quantitative PCR revealed increased ActR-IIa expression following TNFα stimulation and siRNA knockdown of ActR-IIa abrogated this enhanced proliferative response. In summary, TNFα increases BMP6 expression, which in the absence of functional BMPR-II, can bind to receptor complexes involving ActR-IIa to accelerate PASMC proliferation. The potential contribution of this novel mechanism to vascular remodelling in the systemic and pulmonary circulation requires further study.
P218 Nodal Staging In Lung Cancer: A Risk Stratification Model For Lymph Nodes Classified As Negative By Ebus-tbna
Authors: M. Evison, P. Crosbie, J. Morris, J. Martin, R. Shah, P. Barber, R. Booton
Journal: Thorax (2014)

<h3>Background</h3> Over the last 10 years, EBUS-TBNA has become established as the first line nodal staging procedure of choice for lung cancer patients. However, the pathway for patients following a negative EBUS-TBNA has not been clearly defined. <h3>Aims and objectives</h3> The primary aim of this study was to develop and validate a risk stratification model to categorise lymph nodes deemed negative by EBUS-TBNA into ‘low risk’ and ‘high risk’ groups, where ‘risk’ refers to the risk of false negative sampling. <h3>Materials and methods</h3> A retrospective analysis of a prospectively maintained database at a UK tertiary EBUS-TBNA centre. Only patients with primary lung cancer and only negative lymph nodes by EBUS-TBNA were included in the analysis. A risk stratification model was built from a derivation set using independent predictors of malignancy and the validation set used to evaluate the constructed model. The study period was March 2010 to August 2013. <h3>Results</h3> 329 lymph nodes were included in the analysis (derivation set n = 196, validation set n = 133). Lymph node SUV, the SUV ratio between the lymph node and primary tumour and heterogeneous echogenicity during sonographic assessment were the only independent predictors of malignancy. Using a simplified scoring system based on the natural logs of the odds ratios from the multivariable analysis on the derivation sample, lymph nodes can be stratified into ‘low risk’ (score ≤1) and ‘high risk’ (score ≥2). 141/142 and 94/96 lymph nodes classified as ‘low risk’ in the derivation and validation set respectively were ultimately proven to be benign and 35/54 and 24/37 lymph nodes classified as ‘high risk’ were proven malignant. The negative predictive value of the risk stratification model for the derivation set and validation set was 99.3% (95% CI 96.1–99.6) and 97.9% (95% CI 92–99.6%) respectively. <h3>Discussion</h3> This risk stratification model may assist lung cancer MDTs in deciding which patients need further staging procedures and which may proceed directly to treatment after a negative EBUS.
Corner's caring contribution
Authors: M. Robson
Journal: BMJ (1996)

The BBC has obviously realised that the market for programmes about sexy young modern doctors is completely saturated. We've got Casualty, ER, Chicago Hope, Northern Exposure, Country Practice, GOS, Jimmy's—need I go on? Hence the Pioneers series, looking at medical innovators of the 20th century, which continued on BBC2 on Monday with “Beryl's Babies.”

This was a programme about the female founder of the Bristol's first special care baby unit, Dr Beryl Corner. She made an astounding contribution to modern neonatal care with her work on retinopathy of prematurity and kernicterus and achieved all this in an …
Commentary: Health Issues in the Clean Air Act
Authors: Robert Frank
Journal: Environmental Health Perspectives (1983)

Major conclusions and recommendations of the National Commission on Air Quality on issues of health in the Clean Air Act are presented.The issues revolve mainly about the standard setting processes for ubiquitous pollutants, controlled through ambient air quality standards (Section 109), and for hazardous pollutants controlled through emis- sion standards (Section 112).The conceptual difficulties inherent in the terms "adequate margin of safety" (Section 109) and "ample margin of safety" (Section 112) are discussed.The Clean Air Science Advisory Committee is widely viewed as having a salutary effect on standard setting.The need for maintaining strong research capabilities within the Environmental Protection Agency that are reasonably buffered against sudden disruptive events is emphasized.Mechanisms for achieving this goal through special congres- sional appropriations are considered.
PTH-063 Establishing Audit Standards for Colonic Stent Insertion will Facilitate Service Evaluation and Planning for a Rapidly Growing Service
Authors: T M Cacciottolo, D Menzies, A Shenoy, D O’Riordan, I Gooding
Journal: Gut (2013)

<h3>Introduction</h3> Self-expandable metal stent (SEM) placement is the recommended treatment option by the National Institute for Clinical Excellence (NICE) for acute colorectal obstruction in the palliative management of inoperable colorectal cancer (CRC) as well as a bridge to planned single stage surgical intervention[1]. NICE guidance recommends that centres offering this treatment modality should have teams with expertise and capacity to stent 15 people per million population per annum[2]. It does not however provide any suitable standard for audit. <h3>Methods</h3> All colonic stents inserted between 1st January 2008 and 31st December 2011 were included. Patient characteristics, procedure related data, outcomes and survival were recorded retrospectively from health records. <h3>Results</h3> Systematic review of 29 case series of stent insertions reported a clinical success rate of 88%, 10% stent migration rate, 4% perforation rate, 10% reobstruction rate and 1% procedure-related mortality rate[3]. These were applied as our audit standards. A total of 69 colonic stents (in 64 patients, 35 male, mean age 74.2 years) were inserted. 15 stents were inserted in 2008 and this increased steadily to 25 in 2011.The most common indication for colonic stent insertion was a malignant stricture (89.9%). There was a 98.5% technical success rate, 2.9% migration rate, 7.2% perforation rate and a 4.3% reobstruction rate within one month of the procedure. The clinical success rate, ie successful stent insertion and decompression within 96 hours, was 88.4%. 61.1% had stent insertion as a bridge to surgery. Mean survival post procedure was 200 days (range 1–779 days). The were 2 deaths as a direct consequence of the procedure (2.9%), both of which followed perforation in patients who were too frail to undergo surgery. <h3>Conclusion</h3> We have defined and applied audit standards for colonic stent insertion. Success and complication rates at our hospital compare favourably to published rates. There is a steady increase in colonic stent insertions and in our 2011 cohort this equated to 67.6 patients per million per annum. It is likely that this number will continue to increase and endoscopy units should take this into account when planning their service provision. Audit support will be essential, and we encourage the adoption of consistent audit standards to facilitate comparison between units. <h3>Disclosure of Interest</h3> None Declared. <h3>References</h3> National Institute for Health and Clinical Excellence. (2004). Improving Outcomes in Colorectal Cancers. CSGCC. National Institute for Health and Clinical Excellence.(2010). Improving Outcomes in Colorectal Cancers. Manual Update. Khot <i>et al.</i> Systematic Review of the Safety and Efficacy of Colorectal Stents. BJS 2002(89):1096:1102
Detection of Recurrence in Glioma
Authors: Amburanjan Santra, Rakesh Kumar, Punit Sharma, Chandrashekhar Bal, Pramod Kumar Julka, Arun Malhotra
Journal: Clinical Nuclear Medicine (2011)

Early and correct diagnosis of tumor recurrence and its differentiation from therapy-related changes is crucial for prompt and adequate management of glioma patients. The purpose of this study was to compare the efficacies of Tc-99m glucoheptonate (GHA) single photon emission tomography (SPECT) and F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in detection of recurrence in patients with glioma.A total of 90 patients with histopathologically proven glioma who had suspicion of recurrence clinically or on magnetic resonance imaging were evaluated using Tc-99m GHA SPECT and FDG PET/CT. Combination of clinical follow-up, repeat imaging, and biopsy (when available) was taken as gold standard.On the basis of gold standard, 59 patients were positive and 31 were negative for tumor recurrence. The sensitivity, specificity, and accuracy of GHA SPECT were 85%, 97%, and 89%, respectively, whereas those of FDG PET/CT were 70%, 97%, and 80%, respectively. On subgroup analysis, GHA SPECT performed better than FDG PET/CT in all grades except for grade II gliomas, where both were equally effective. In all, 15 patients had intermodality discordance, with GHA SPECT being correct in 13 of them.GHA SPECT appears to be a better imaging modality than FDG PET/CT for detection of recurrent gliomas.
Salmonella Osteomyelitis of the Spine Associated with Abdominal Aortic Aneurysm
Authors: Klaus R. Dehlinger
Journal: New England Journal of Medicine (1948)

THE occurrence of an abdominal aortic aneurysm and associated Salmonella osteomyelitis of the spine seems of sufficient interest to warrant a report in some detail, together with autopsy findings.Case ReportI. P., a 69-year-old married Albanian dishwasher, was admitted to the hospital on November 10, 1945. He had apparently been in excellent health until 6 days before admission, when headaches, nausea and vomiting developed and the stools became loose but not watery. After 2 days the bowel movements were apparently normal again. For the next 3 days he experienced several shaking chills with a maximum temperature of 103°F.The . . .
PRIMER CONTACTO CON LA D.S.E. EN MODELO PORCINO: ¿MEJORA LA VELOCIDAD DE DISECCIÓN CON UN DISPOSITIVO DE ASISTENCIA EN LA FASE DE DISECCIÓN SUBMUCOSA?
Authors: JC Marín-Gabriel, S Rodríguez-Muñoz, F Soria-Gálvez, C Martín-García, M Fernández Bermejo, JM Mateos-Rodríguez, R Latorre-Reveriego, FM Sánchez-Margallo, G Castellano-Tortajada
Journal: Endoscopy (2011)

Objetivo: Evaluar si el uso de Endolifter (Olympus; Tokyo, Japón) facilita la realización de la D.S.E. en modelo porcino en endoscopistas sin experiencia en esta técnica.
Innovative applications of immunisation registration information systems: example of improved measles control in Taiwan
Authors: D P Liu, E T Wang, Y H Pan, S H Cheng
Journal: Eurosurveillance (2014)

Immunisation registry systems have been shown to be important for finding pockets of under-immunised individuals and for increasing vaccination coverage. The National Immunisation Information System (NIIS) was established in 2003 in Taiwan. In this perspective, we present the construction of the NIIS and two innovative applications, which were implemented in 2009, which link the NIIS with other databases for better control of measles. Firstly, by linking the NIIS with hospital administrative records, we are able to follow up contacts of measles cases in a timely manner to provide the necessary prophylaxis, such as immunoglobulin or vaccines. Since 2009, there have been no measles outbreaks in hospitals in Taiwan. Secondly, by linking the NIIS with an immigration database, we are able to ensure that young citizens under the age of five years entering Taiwan from abroad become fully vaccinated. Since 2009, the measles-mumps-rubella vaccine coverage rate at two years of age has increased from 96% to 98%. We consider these applications of the NIIS to be effective mechanisms for improving the performance of infectious disease control in Taiwan. The experience gained could provide a valuable example for other countries.
Abstract 5002: Intermittent hypoxia selects for increased carcinogenicity in breast epithelial cells.
Authors: Daniel Verduzco, Robert Gatenby, Robert Gillies
Journal: Cancer Research (2013)

Abstract The hypoxic regions of solid tumors are hotbeds of drug resistance and selection. Tumors with highly hypoxic regions correlate with poor prognosis and increased aggressiveness. The exact molecular mechanisms of selection have not been elucidated. Recent studies have demonstrated that reoxygenation causes widespread DNA damage. Additionally, hypoxia suppresses the DNA damage machinery. Because cells within a solid tumor do not receive a consistent amount of oxygen, cycles of acute hypoxia and reoxygenation occur, a phenomenon termed intermittent hypoxia (IH). We predict that this may lead to widespread unrepaired DNA damage that consistently selects for populations adapted to survive within harsh tumor microenvironmental conditions. We tested three breast cell lines - one aggressive carcinoma (MB 231), one DCIS line, and one non-transformed epithelial cell line (MCF10A) - for DNA damage and transformation after multiple cycles of IH. Cells were incubated under 0.2% hypoxia for 16 hours and reoxygenated for 8, for multiple cycles. Multiple clones of each cell line selected under IH conditions were then isolated. MCF10A IH-selected clones exhibit increased resistance to etoposide relative to unselected clones. Two of these clones were selected for additional phenotyping, and exhibited constituitive carbonic anhydrase 9 expression, as measured by qRT-PCR. Resistance to methotrexate, docetaxel, and hypoxia induced cell death was also observed, but growth-factor independent proliferation was not detected. Additionally, genomic analyses have revealed loss of the tp53 and e-cadherin loci after intermittent hypoxia. Consistent with this, we detect loss of p53 and e-cadherin mRNA levels and anchorage independent growth. These data increase our understanding of why hypoxia creates more aggressive cancers and poorer prognoses, and how de novo drug resistance arises. Citation Format: Daniel Verduzco, Robert Gatenby, Robert Gillies. Intermittent hypoxia selects for increased carcinogenicity in breast epithelial cells. [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 5002. doi:10.1158/1538-7445.AM2013-5002
New system for assessing the prognosis of refractory anemia patients
Authors: A Matsuda, I Jinnai, F Yagasaki, S Kusumoto, I Murohashi, M Bessho, K Hirashima, S Honda, M Minamihisamatsu, K Fuchigami, T Matsuo, K Kuriyama, M Tomonaga
Journal: Leukemia (1999)
F-18 FDG positron emission tomographic imaging in bilateral iliopsoas abscesses.
Authors: Chan H. Park, Myoung-Hoon Lee, Chang-Guan Oh
Journal: Clinical Nuclear Medicine (2002)

F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has been effective for imaging tumor and inflammatory lesions. Psoas abscess is rare and has a vague clinical presentation. The authors describe a 16-year-old boy who had Ga-67 scan findings typical of bilateral iliopsoas abscesses resulting from tuberculosis. The FDG-PET findings were similar to those of Ga-67 scans and the diagnosis was confirmed by pelvic computed tomography.
The reasonable calculation of complete enteroscopy rate for balloon-assisted enteroscopy
Authors: L. Xin, Y. Gao, Z. Liao, Z. Li
Journal: Endoscopy (2011)

In a recent article published online in Endoscopy, Möschler et al. [1] reported the results of complications and performance of double-balloon endoscopy (DBE) examinations in Germany. A remarkable aspect of the procedural data was the low rate of complete enteroscopy, which was only achieved in 23 % of patients undergoing either the oral approach alone or combined oral and anal DBE. The complete enteroscopy rate has been used as an objective parameter to evaluate the performance of balloon-assisted enteroscopy in two other studies published recently [2] [3]. There are several aspects we would like to discuss.