tbuckley/cabot-search huggingface dataset:
P101 Regulatory T cells exhibit reduced phenotypic stability upon pro-inflammatory challenge in autoimmune hepatitis
Authors: C. R. Grant, B. Holder, Y. Ma, G. Mieli-Vergani, D. Vergani, M. S. Longhi
Journal: Gut (2011)

<h3>Introduction</h3> In autoimmune hepatitis (AIH) CD4<sup>+</sup>CD25<sup>high</sup> regulatory T-cells (Tregs) are numerically defective and fail to suppress T-cell-mediated immune responses. Expression by Tregs of the ectoenzyme CD39 contributes to their ability to suppress by initiating an ATP hydrolysis cascade which leads to the production of adenosine, a molecule with inhibitory properties. Recently expression of CD39 has been associated with T-reg phenotypic stability under inflammatory conditions. <h3>Aim</h3> To investigate the frequency and phenotypic stability of CD39<sup>+</sup> Tregs in AIH. <h3>Method</h3> 24 AIH patients (23 ANA/SMA<sup>+</sup>, 1 LKM-1<sup>+</sup>; 12 females, median age: 15 years) and 24 healthy subjects (HS; 16 females, median age: 35 years) were studied. The phenotype of circulating Tregs was assessed by flow cytometry using monoclonal antibodies to CD4, CD25, CD127, CD39 and CD73, an ectonucleotidase that in mice is expressed by Tregs and works in tandem with CD39. The frequency of IFNγ, IL10 and IL17-producing cells within Tregs was determined by intracellular staining. Analysis was performed at baseline and after exposure to anti-CD3/CD28 T-cell expander or to the pro-inflammatory cytokines IL1β and IL6 (IL1β+IL6). <h3>Results</h3> At baseline, CD39<sup>+</sup>Tregs were less numerous in AIH (8.78±0.77) than HS (11.93±1.04, P=0.019) and displayed a trend towards higher CD127 expression (7.41±3.25 vs 2.75±1.33, p=0.13) and reduced FOXP3 mean fluorescence intensity (1230±260 vs 997±232, p=0.09). CD73 expression on CD39<sup>+</sup>Tregs did not differ between the two groups. Exposure to T-cell expander increased the frequency of IFNγ<sup>+</sup>CD39<sup>+</sup>Tregs in AIH (from 7.37±2.15 to 24.3±13.37, p=0.043) but not in HS (12.4±2.9 to 6.6±2.4, p=NS). Although the frequency of IFNγ<sup>+</sup>CD39<sup>+</sup>Tregs augmented after treatment with IL1β+IL6 in both AIH (from 7.37±2.15 to 72.9±9.42, p&lt;0.001) and HS (12.39±2.94 to 56.51±16.12, p&lt;0.001), the increase was higher in the former than in the latter (10-fold vs fivefold). IL1β+IL6 increased the frequency of CD127<sup>+</sup>CD39<sup>+</sup>Tregs in AIH (from 4.95±2.23 to 19.6±11.43, p=0.05) but not in HS (2.7±1.3 to 1.3±0.8 p=NS). No change in the frequency of IL10<sup>+</sup> and IL17<sup>+</sup>CD39<sup>+</sup>Tregs was noted upon T-cell expander or IL1β+IL6 stimulation in AIH and HS. <h3>Conclusion</h3> Compared to HS, Tregs from AIH patients display lower CD39 expression and are more prone to become activated upon exposure to pro-inflammatory stimuli, a finding which indicates reduced phenotype stability. A decrease in CD39 expression and in phenotypic stability may contribute to impaired Treg suppressive function in AIH.
P2-15-02: Are We Performing More Mastectomies on Women Diagnosed with Invasive Breast Cancer?
Authors: MCI Lo, B Hariri, T Gandamihardja, J Lewis, K Hogben
Journal: Cancer Research (2011)

Abstract Introduction: Surgical management of breast cancer has changed over the past several decades; breast-conserving surgery has become widely accepted. Mastectomies, however, are still being performed as part of the management of breast cancer. The aim of this study was to investigate the indications for mastectomy in women with invasive breast cancer within our institution. Method: A systematic review of all new patients with invasive breast cancer treated with surgical intervention at our breast unit in the years 2000, 2005 and 2009 was performed. Using our databases, patient demographics, tumour characteristics and reasons for mastectomy were examined. Screen-detected and symptomatic patients were included in the study. Patients excluded were those with incomplete data and recurrent breast cancer. Results: A total of 584 patients (F:M, 576:8); with cancer types which included invasive ductal carcinoma (n=501, 84%), invasive lobular carcinoma (n=51, 9%), invasive tubular carcinoma (n=27, 5%) and sarcomas (n=5, 1%) were studied. Conclusion: In our institution, the majority of patients with screen-detected invasive breast cancer fulfilled the criteria to have breast-conserving surgery; mastectomy rate for screen-detected cancers remained stable. However, we found that in the symptomatic patient group, there was an increase in mastectomy rate from 16% (n=170) in 2000 to 52% (n=225) in 2009. Despite this trend, our results were still in keeping with the national standard as illustrated by the National Cancer Intelligence Network, where they noted that in 2006, 52% of symptomatic patients with invasive breast cancer underwent mastectomy in the United Kingdom. The reason for a higher mastectomy rate in symptomatic patients compared to screen-detected patients in 2009 is multifactorial. We found that a larger proportion of symptomatic patients presented with larger tumours and tumours which were multifocal in nature. Other factors which may have contributed included more accurate estimation of tumour size by imaging (e.g. MRI) and patient choice. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-02.
Laparoscopic Surgery in Infertile Women with Minimal or Mild Endometriosis
Authors: Sylvie Marcoux, Rodolphe Maheux, Sylvie Bérubé
Journal: New England Journal of Medicine (1997)

Minimal or mild endometriosis is frequently diagnosed in infertile women. It is often treated by resection or ablation of the lesions, but whether this improves fertility has not been established. We carried out a randomized, controlled trial to determine whether laparoscopic surgery enhanced fecundity in infertile women with minimal or mild endometriosis.We studied 341 infertile women 20 to 39 years of age with minimal or mild endometriosis. During diagnostic laparoscopy the women were randomly assigned to undergo resection or ablation of visible endometriosis or diagnostic laparoscopy only. They were followed for 36 weeks after the laparoscopy or, for those who became pregnant during that interval, for up to 20 weeks of pregnancy.Among the 172 women who had resection or ablation of endometriosis, 50 became pregnant and had pregnancies that continued for 20 weeks or longer, as compared with 29 of the 169 women in the diagnostic-laparoscopy group (cumulative probabilities, 30.7 percent and 17.7 percent, respectively; P=0.006 by the log-rank test). The corresponding rates of fecundity were 4.7 and 2.4 per 100 person-months (rate ratio, 1.9; 95 percent confidence interval, 1.2 to 3.1). Fetal losses occurred in 20.6 percent of all the recognized pregnancies in the laparoscopic-surgery group and in 21.6 percent of all those in the diagnostic-laparoscopy group (P=0.91). Four minor operative complications (intestinal contusion, slight tear of the tubal serosa, difficult pneumoperitoneum, and vascular trauma) were reported (three in the surgery group and one in the control group).Laparoscopic resection or ablation of minimal and mild endometriosis enhances fecundity in infertile women.
SAT0050 Voice Impairment in Rheumatoid Arthritis Patients: A Disease Activity Marker Often Overlooked
Authors: A. Abou-Raya, S. Abou-Raya, M. Helmii, A. AbdKareem
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) may lead to voice impairment through several anatomical and functional alterations. <h3>Objectives</h3> To evaluate the prevalence of voice impairment in RA patients and to determine the correlation with disease activity and impact on quality of life. <h3>Methods</h3> One hundred and sixteen consecutive RA patients (98 females, 18 males), mean age 54.9 years and mean disease duration 11.5 years attending routine rheumatology outpatient clinics were assessed for current RA activity by disease activity score 28 (DAS28), functional status by health assessment questionnaire disability index (HAQ-DI) and completed the Voice Handicap Index-10 (VHI-10). The inflammatory markers erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed. High resolution computed tomography (HRCT) was performed to assess the cricoarytenoid joint (CTJ). Vocal symptoms such as hoarseness, loss of range and vocal fatigue were assessed. A control group age-sex matched individuals with no voice or autoimmune abnormalities was included. <h3>Results</h3> The prevalence of voice symptoms amongst RA patients was 31% compared to 5% in the control group, p &lt; 0.01. RA patients had significantly higher VHI-10 scores compared to controls, p&lt; 0.05. A significant correlation was noted between VHI-10 scores and DAS scores and HAQ-DI scores respectively. The inflammatory markers ESR and CRP were significantly higher in patients compared to controls. Furthermore, a significant correlation was noted between disease duration and VHI-10 scores (r = 0.578; p&lt; 0.01). HRCT showed significant affection of the CTJ in patients; with 54% demonstrating narrowing of the joint and 37% had increase in CTJ density. <h3>Conclusions</h3> The findings demonstrate an increased prevalence of voice impairment in RA patients. Voice impairment correlated with disease activity, functional disability and inflammation. The implication of the findings of the present study is that voice impairment is an often overlooked problem. Health care professionals should be vigilant about assessing for voice impairment as in addition to impairing quality of life, voice impairment may well be a marker of disease activity. <h3>Disclosure of Interest</h3> None Declared
Abstract P1-13-12: [bold]The adjuvant PANTHER study - A randomized comparison between dose-dense and tailored epirubicin (E), cyclophosphamide (C) and docetaxel (D) vs. standard dose 5-fluorouracil (F), epirubicin (E), cyclophosphamide (C) and docetaxel – First report on q
Authors: Yvonne Brandberg, Nils-Olof Bengtsson, Richard Greil, Volker Möbus, Per Malmström, Hemming Johansson, Harald Andersson, Mats Hellström, Michael Gnant, Gunter von Minckwitz, Jonas Bergh
Journal: Cancer Research (2012)

Abstract Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-12.
Abstract 3582: Licochalcone-A, a natural inhibitor of c-Jun N-terminal kinase 1.
Authors: Ke Yao, Hanyong Chen, Mee-Hyun Lee, Haitao Li, Weiya Ma, Ki Won Lee, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2013)

Abstract The c-Jun N-terminal kinases (JNKs) pathway plays an important role in many physiological processes induced by a variety of stress signals. Each JNK protein appears to have a distinct function in cancer, asthma, diabetes, or Parkinson's disease. JNK1 is a key contributor for breast cancer and gastric cancer. Herein, we found that licochalcone-A, a major phenolic constituent isolated from licorice root, suppressed JNK1 activity, but had little effect on JNK2 in vitro. Although licochalcone-A binds with JIP1 competitively with either JNK1 or JNK2, a computer simulation model showed that after licochalcone-A binding, the ATP-binding cleft of JNK1 was distorted more substantially than that of JNK2. This could reduce the affinity of JNK1 more than JNK2 for ATP binding. Furthermore, licochalcone-A inhibited JNK1-mediated, but not JNK2-mediated, c-Jun phosphorylation in both ex vivo and in vitro systems. We also observed that in colon and pancreatic cancer cell lines, JNK1 is highly expression compared with normal cell lines. In these cell lines, treatment with licochalcone-A or knocking down JNK1 expression suppressed colon and pancreatic cancer cell proliferation and colony formation. These results demonstrate that licochalcone-A is a selective JNK1 inhibitor. Therefore, we suggest that because of JNK1’s critical role in colon cancer and pancreatic carcinogenesis, licochalcone-A might have therapeutic potential against this devastating disease. Citation Format: Ke Yao, Hanyong Chen, Mee-Hyun Lee, Haitao Li, Weiya Ma, Ki Won Lee, Ann M. Bode, Zigang Dong. Licochalcone-A, a natural inhibitor of c-Jun N-terminal kinase 1. [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 3582. doi:10.1158/1538-7445.AM2013-3582
Abstract 3099: Gastroesophageal junction adenocarcinoma displays abnormalities in homology directed repair
Authors: Robin I. Dewalt, Kenneth A. Kesler, Shadia I. Jalal
Journal: Cancer Research (2012)

Abstract The incidence of adenocarcinoma of the gastroesophageal (GE) junction has risen dramatically over the last three decades. Outcomes continue to be poor with 5 year survivals estimated at 15%. These poor outcomes are related to the advanced presentation in the majority of patients in addition to the resistance esophageal adenocarcinoma displays to cisplatin based chemotherapy or radiation especially when each is administered alone. Only one-third of patients will have significant benefit and achieve complete responses when treated with the combination of cisplatin-based chemotherapy and radiation followed by surgical resection. Therefore, the need persists for overcoming resistance to cisplatin-based chemotherapy and radiation. Previous studies have highlighted the role of DNA repair pathways in resistance to cisplatin or radiation in a number of solid organ malignancies. The nucleotide repair pathway (NER) repairs the majority of cisplatin-induced DNA lesions while DNA double-strand breaks (DSBs) formed in response to radiation are repaired by homologous recombination (HR) and the non-homologous end-joining (NHEJ) pathways. We hypothesized that cisplatin and radiation resistance in esophageal adenocarcinoma is mediated through abnormalities in these DNA repair pathways. Using paired GE junction adenocarcinoma tumor samples with their matched normal tissue, we analyzed the expression of DNA repair genes in NER, HR and NHEJ pathways using quantitative RT-PCR. We identified overexpression of genes involved in HR in esophageal tumor samples in comparison to their normal counterparts. Eme1, an endonuclease present in complex with Mus81, showed consistent overexpression in GE junction adenocarcinoma samples. Mus81-Eme1 has been shown to play an important role in rescuing stalled replication forks and has been implicated in the repair of interstrand crosslinks, such as those formed in response to cisplatin therapy. Eme1 overexpression in esophageal adenocarcinoma could play a role in resistance to cisplatin through its impact on the repair of cisplatin induced DNA lesions. In addition, Eme1 overexpression could lead to genomic instability contributing to pathogenesis, metastases and therapeutic resistance. Further understanding the implications of Eme1 overexpression in these processes in GE junction adenocarcinoma will be of significant value. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3099. doi:1538-7445.AM2012-3099
Case 43-1970
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Charles A. Sanders, Benjamin Castleman
Journal: New England Journal of Medicine (1970)

Presentation of CaseA 62-year-old man was brought to the hospital because of collapse.He had enjoyed good health in the past but for two months before admission had felt vaguely less well than usual. During the week before entry he noticed soreness of the neck, and two days before admission he thought that he might be "coming down with a cold." On the evening of entry, after dinner and his customary game of chess, he had the abrupt onset of profound weakness, with a generalized sensation of warmth, dizziness and nausea; there was no pain in the chest or . . .
Prevalence of a Polymorphism of the Phosphatidylinositol 3-Kinase p85α Regulatory Subunit (Codon 326Met→ile) in Japanese NIDDM Patients
Authors: Masatoshi Kawanishi, Yoshikazu Tamori, Jiro Masugi, Hiroyuki Mori, Chikako Ito, Torben Hansen, Carsten B Andersen, Oluf Pedersen, Masato Kasuga
Journal: Diabetes Care (1997)
Case 16-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, James H. Chesebro, Richard L. Morrissey, John T. Fallon
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 57-year-old woman was admitted to the hospital because of dyspnea, chest pain, and a mass in the right atrium and ventricle.The patient had been well until three days earlier, when she experienced the onset of dyspnea, which persisted. That night she was awakened by severe right-sided pleuritic chest pain. On the following day the pain recurred, and she coughed up gross blood; she was admitted to another hospital.The hematologic laboratory values are presented in Table 1. The lactate dehydrogenase level was 1119 U per liter (normal, 313 to 618). The values for urea nitrogen, creatinine, . . .
Abstract 3584: Comparison of the severity of imatinib-induced cardiotoxicity in normotensive Sprague-Dawley (SD) and spontaneously hypertensive (SHR) rats
Authors: Eugene H. Herman, Alan Knapton, Elliot Rosen, Jun Zhang, Quynh A. Lu, Joel Estis, John Todd, Steven Lipshultz
Journal: Cancer Research (2010)

Abstract Imatinib (IMNB) is a promising type of chemotherapeutic agent that specifically targets tyrosine kinase pathway-dependent tumors. However, cardiotoxicity has been reported with clinical use of IMNB. The characteristics of IMNB-induced cardiac alterations are not completely defined. The present study sought to examine the influence of a concomitant disease such as hypertension on the cardiotoxic effects of IMNB. Groups of adult male SD or SHR were dosed with 50 (5/group) or 100 mg/kg (10/group) IMNB or water (10/group)(p.o.) daily for 14 days (dose of 50 mg/kg is approximately 2x recommended human dose of 600 mg/m2). Tissues and blood samples were collected 24 hours after the last dosing. The 100 mg/kg dose caused a slight reduction in the rate of body weight gain. Serum levels of glucose were decreased and alanine transaminase (ALT) were increased in both SD and SHR dosed with IMNB. Changes from control were most pronounced in SD given 100mg/kg IMNB (ALT=175% vs 118% and glucose=81% vs 91% compared to SHR). White blood cell counts were depressed in SHR but not in SD rats. Dose-dependent cardiac lesions were noted in the groups of SD and SHR given either dose of IMNB (blinded evaluation). Cardiac lesions were characterized by cytoplasmic vacuolization, myofibrillar loss, interstitial infiltration with chronic inflammatory cells and fibrosis (proliferation of myofibroblasts). Mean lesion scores (based on a scale of 0 to 3) were higher in SHR than in SD (100mg/kg-1.9 vs 1.25 and 50 mg/kg-1.5 vs 1.1, p&amp;lt;0.05)(Tukey-Kramer test). Increased serum levels of cardiac troponin I were detected in all IMNB-treated groups. The overall mean cTnI levels were higher in SHR (31.5, 41.3 and 53.9 pg/ml) compared to SD (6.8, 25 and 30 pg/ml) at the vehicle control, 50 and 100 mg/kg doses, respectively. These results indicate that hypertension as expressed in SHR appears to be a factor that can intensify the cardiotoxic effects of IMNB and that monitoring for cardiac troponin I may provide a sensitive means of detecting IMNB toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3584.
Abstract LB-240: A novel approach to detecting RNA expression in living breast cancer cells.
Authors: Don Weldon, Kevin Su, Alex Ko, Grace Johnston, Matthew Hsu, Lucas Armstrong
Journal: Cancer Research (2013)

Abstract When studying the complexities of cancer biomarkers, the ability to monitor gene expression within live cells that have become cancerous provides better insight than examining fixed or lysed tissues. However, monitoring RNA within intact cells can prove to be challenging with current techniques, which involve complex RNA isolation procedures that compromise cell viability. Further, amplification methods can create false positives or erroneously inflate differences. Here we describe a probe-based detection method that allows for the detection of ErbB-2 and EGFR mRNA levels across live intact SK-BR-3 breast cancer cells without the need for transfection reagents. The detection methodology is based upon an oligonucleotide gold nanoparticle conjugate capable of detecting intracellular levels of mRNA and miRNA in living cells. The probes enter the cell by means of the cell's native endocytosis machinery. Upon binding to the complementary target RNA sequence, a fluorescent signal (flare) is released, which allows the cells to be detected on any fluorescence analysis platform. In contrast to traditional RNA detection methods, since our technique allows for detection within live cells without altering their gene expression, the same cells that were profiled for EGFR and ErbB-2 expression could be sorted based on their specific mRNA content and subsequently further studied. Stimulation or treatments could then be performed on the previously profiled cells and assessed using probes for additional RNA markers or more traditional techniques such as antibody staining, qRT-PCR, or Array profiling. For this purpose, we combined immunostaining for cell surface EGFR with fluorogenic nanoparticle-based detection of EGFR mRNA in 4 breast cancer cell lines known to range in EGFR expression levels, and observed significant correlation for the signals in two-color flow cytometry. Thus, detecting RNA expression levels in live cancer cells with the ability to utilize the same cells in downstream testing gives researchers the ability to perform experiments which were previously thought to be impossible. Citation Format: Don Weldon, Kevin Su, Alex Ko, Grace Johnston, Matthew Hsu, Lucas Armstrong. A novel approach to detecting RNA expression in living breast cancer 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 LB-240. doi:10.1158/1538-7445.AM2013-LB-240
A strangulated hernia as a result of ERCP
Authors: J. Horsnell, V. Pegna, A. Bell, A. Mickevicius
Journal: Endoscopy (2013)

An 83-year-old woman attended for endoscopic retrograde cholangiopancreatography (ERCP) following an episode of acute jaundice. A computed tomography (CT) scan confirmed a dilated common bile duct with a distal filling defect that was later confirmed on magnetic resonance imaging (MRI) to be a biliary stone. She had undergone a right inguinal hernia repair 5 years previously and the CT scan suggested a possible recurrence ([Fig. 1]).
CURRENT TREND OF FACTORS INFLUENCING PHYSICIAN PREFERENCE IN RADIAL VERSUS FEMORAL ACCESS IN ANGIOGRAPHY: A REAL WORLD EXPERIENCE FROM A TERTIARY CARE TEACHING HOSPITAL
Authors: Jimmy Yee, Vishesh Kumar, Pujan Patel, Neil Patel, Paul Thompson, Adam Stys, Marian Petrasko, Tomasz Stys
Journal: Journal of the American College of Cardiology (2016)