tbuckley/cabot-search huggingface dataset:
Abdominal pain after attempted endoscopic mucosal resection of a right-sided colonic lesion
Authors: S Sarkar, V Tagore, D White
Journal: Gut (2008)

During a routine colonoscopy in a 61-year-old male, a 1.5 cm sessile polyp was found within the caecum. A submucosal injection consisting of 20.5 ml containing adrenalin (2 ml of 1:10 000), gelofusin (18 ml) and methylene blue (0.5 ml) was administered …
World Health Organization-Defined Metabolic Syndrome Is a Better Predictor of Coronary Calcium Than the Adult Treatment Panel III Criteria in American Men Aged 40–49 Years
Authors: Tomoko Takamiya, Wahid R. Zaky, Daniel Edmundowics, Takashi Kadowaki, Hirotsugu Ueshima, Lewis H. Kuller, Akira Sekikawa
Journal: Diabetes Care (2004)

Detection of coronary artery disease, a major cause of death in the U.S., is important in primary prevention settings. The noninvasive screening method of electron beam-computed tomography (EBCT) can be used to quantify coronary arterial calcification (CAC) and identify subjects with subclinical coronary artery atherosclerosis (1,2). However, EBCT screenings of all asymptomatic subjects is not practical in the clinical setting (3,4). Therefore, identification of high-risk subjects before EBCT evaluation is necessary. Currently, the metabolic syndrome, a constellation of risk factors, is used to identify high-risk individuals over and above conventional coronary risk factors because of the independent association of the metabolic syndrome with subsequent development of cardiovascular diseases and diabetes (5–10). The purpose of this study was 1 ) to determine whether risk identification using metabolic syndrome as a criterion is useful for the detection of CAC with EBCT and 2 ) to compare the usefulness of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III) guidelines (5) definition of metabolic syndrome with the World Health Organization (WHO) (8) definition.

We examined 100 male residents in Allegheny County, Pennsylvania, aged 40–49 years, without evidence of clinical cardiovascular disease, diabetes, cancer, renal failure, or familial hyperlipidemias. …
Increased Levels of Interleukin-18 in Patients with Pulmonary Sarcoidosis
Authors: KATSUNORI SHIGEHARA, NORIHARU SHIJUBO, MITSUHIDE OHMICHI, GEN YAMADA, RYUJI TAKAHASHI, HARUKI OKAMURA, MASASHI KURIMOTO, YOUMEI HIRAGA, TACHIO TATSUNO, SHOSAKU ABE, NORIYUKI SATO
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Interleukin-18 (IL-18) has recently been identified as an interferon-gamma (IFN-gamma)-inducing factor, and it plays an important role in T helper 1 (Th1) response. We measured the serum levels of IL-18 and IFN- gamma in 37 patients with pulmonary sarcoidosis and 25 healthy control subjects. We also measured the levels of IL-18 and IFN-gamma in 10-fold concentrated bronchoalveolar lavage (BAL) fluids of 19 patients with pulmonary sarcoidosis and 9 healthy control subjects (all lifelong nonsmokers). The levels of serum IL-18 and IFN-gamma were significantly increased in patients with sarcoidosis. The levels of BAL fluid IL-18 were significantly elevated in patients with sarcoidosis, however, the IFN-gamma levels of the patients and control subjects were all below sensitivity. Serum IL-18 levels significantly correlated with serum IFN-gamma levels and lysozyme activity. The patients positive for gallium-67 ((67)Ga) scan had significantly elevated serum IL-18 levels as compared with those of the negative patients. BAL fluid IL-18 levels significantly correlated with serum IL-18 levels in patients with sarcoidosis, and there was a significant correlation between IL-18 levels and lymphocyte proportions in sarcoid BAL fluids. In patients with sarcoidosis, IL-18 seems to induce IFN-gamma production and IL-18 levels in sera may reflect disease activity of sarcoidosis.
Activation of the mTOR Pathway in Primary Medullary Thyroid Carcinoma and Lymph Node Metastases
Authors: Anna Tamburrino, Alfredo A. Molinolo, Paolo Salerno, Rebecca D. Chernock, Mark Raffeld, Liqiang Xi, J. Silvio Gutkind, Jeffrey F. Moley, Samuel A. Wells, Massimo Santoro
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Understanding the molecular pathogenesis of medullary thyroid carcinoma (MTC) is prerequisite to the design of targeted therapies for patients with advanced disease. Experimental Design: We studied by immunohistochemistry the phosphorylation status of proteins of the RAS/MEK/ERK and PI3K/AKT/mTOR pathways in 53 MTC tissues (18 hereditary, 35 sporadic), including 51 primary MTCs and 2 cases with only lymph node metastases (LNM). We also studied 21 autologous LNMs, matched to 21 primary MTCs. Staining was graded on a 0 to 4 scale (S score) based on the percentage of positive cells. We also studied the functional relevance of the mTOR pathway by measuring cell viability, motility, and tumorigenicity upon mTOR chemical blockade. Results: Phosphorylation of ribosomal protein S6 (pS6), a downstream target of mTOR, was evident (S ≥ 1) in 49 (96%) of 51 primary MTC samples. This was associated with activation of AKT (phospho-Ser473, S &amp;gt; 1) in 79% of cases studied. Activation of pS6 was also observed (S ≥ 1) in 7 (70%) of 10 hereditary C-cell hyperplasia specimens, possibly representing an early stage of C-cell transformation. It is noteworthy that 22 (96%) of 23 LNMs had a high pS6 positivity (S ≥ 3), which was increased compared with autologous matched primary MTCs (P = 0.024). Chemical mTOR blockade blunted viability (P &amp;lt; 0.01), motility (P &amp;lt; 0.01), and tumorigenicity (P &amp;lt; 0.01) of human MTC cells. Conclusion: The AKT/mTOR pathway is activated in MTC, particularly, in LNMs. This pathway sustains malignant features of MTC cell models. These findings suggest that targeting mTOR might be efficacious in patients with advanced MTC. Clin Cancer Res; 18(13); 3532–40. ©2012 AACR.
Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid
Authors: Grant Theron, Jonny Peter, Richard Meldau, Hoosain Khalfey, Phindile Gina, Brian Matinyena, Laura Lenders, Gregory Calligaro, Brian Allwood, Gregory Symons, Ureshnie Govender, Mashiko Setshedi, Keertan Dheda
Journal: Thorax (2013)

<h3>Rationale</h3> The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. <h3>Methods</h3> South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (∼10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. <h3>Results</h3> 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p&lt;0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18–41) to 0 (0–0); p&lt;0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1–49) versus 7 (0–21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. <h3>Conclusions</h3> MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.
Briefly Noted. Transmembrane Signaling. Proceedings of the ICN-UCLA Symposium, Keystone, Colorado, February 26-March 3,1978. Edited by M. Bitensky, R. J. Collier, D. F. Steiner, and C. F. Fox. New York: Liss, 1979. $94.00.
Authors: C. S. Davidson
Journal: Hepatology (1982)
Zalcitabine Compared with Zidovudine in Patients with Advanced HIV-1 Infection Who Received Previous Zidovudine Therapy
Authors: Margaret A. Fischl
Journal: Annals of Internal Medicine (1993)

Objective: To evaluate the safety and efficacy of zalcitabine (also known as dideoxycytidine [ddC]) in patients with advanced human immunodeficiency virus (HIV) infection. Design: Open-label, randomized study. Setting: AIDS Clinical Trials Units, university-affiliated medical centers, and private practice groups. Patients: Patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex who had tolerated zidovudine for 48 weeks or more. Intervention: Fifty-nine patients received zidovudine (500 to 1200 mg/d) and 52 patients received zalcitabine (2.25 mg/d). Measurements: The primary end points were survival and time to an AIDS-defining event or death. Results: Because significantly more patients withdrew from zidovudine therapy, the median duration of treatment was greater in the zalcitabine group than in the zidovudine group (279.0 days compared with 174.5 days; P = 0.001). The estimated 12-month, event-free probabilities were 53% for the zalcitabine group and 57% for the zidovudine group (relative risk, 1.02; 95% CI, 0.5 to 2.2). The estimated 12-month survival rates were 81% for the zalcitabine group and 75% for the zidovudine group (relative risk, 1.39; CI, 0.5 to 3.8). The rate of decline in CD4 lymphocyte counts was significantly slower in the zalcitabine group than in the zidovudine group ( 0.08 cells/day compared with 0.17 cells/day). Patients in the zalcitabine group had gained an average of 0.5 kg at week 20 and 0.4 kg at week 24, whereas patients in the zidovudine group had lost an average of 1.8 kg at week 20 and 2.4 kg at week 24 (P = 0.04 and P = 0.05, respectively). Moderate to severe peripheral neuropathy and ulcerative stomatitis occurred in 10 and 9 patients, respectively, in the zalcitabine group. Conclusions: The sample size for this study was smaller than planned, and no differences in survival and clinical end points were found. Slower rates of decline in CD4 lymphocyte counts and weight, however, were noted for the zalcitabine group. *Other participants are listed in the Appendix. For current author addresses, see end of text.
Once-daily indacaterol<i>versus</i>twice-daily salmeterol for COPD: a placebo-controlled comparison
Authors: O. Kornmann, R. Dahl, S. Centanni, A. Dogra, R. Owen, C. Lassen, B. Kramer
Journal: European Respiratory Journal (2010)

Indacaterol is a novel, inhaled, once-daily, ultra-long-acting β 2 -agonist bronchodilator recently approved in Europe for the treatment of chronic obstructive pulmonary disease (COPD). The aim of the present study was to investigate the efficacy and safety of indacaterol compared with placebo and the twice-daily β 2 -agonist, salmeterol, as an active control. Patients with moderate-to-severe COPD were randomised to 6 months double-blind treatment with indacaterol (150 μg once daily), salmeterol (50 μg twice daily) or placebo. The primary efficacy end-point was trough (24 h post-dose) forced expiratory volume in 1 s (FEV 1 ) after 12 weeks. 1,002 patients were randomised and 838 (84%) completed the study. Indacaterol increased trough FEV 1 at week 12 by 170 mL over placebo (p&lt;0.001) and by 60 mL over salmeterol (p&lt;0.001). Both active treatments improved health status (St George's Respiratory Questionnaire) and dyspnoea (transition dyspnoea index) compared with placebo, with differences between them favouring indacaterol. Safety profiles were similar across the treatment groups, and both indacaterol and salmeterol were well tolerated. Once-daily treatment with 150 μg indacaterol had a significant and clinically relevant bronchodilator effect over 24 h post-dose and improved health status and dyspnoea to a greater extent than twice-daily 50 μg salmeterol. Indacaterol should prove a useful additional treatment for patients with COPD.
A potential mechanism of "cross-talk" between the p55 tumor necrosis factor receptor and Fas/APO1: proteins binding to the death domains of the two receptors also bind to each other.
Authors: E E Varfolomeev, M P Boldin, T M Goncharov, D Wallach
Journal: The Journal of Experimental Medicine (1996)

The p55 tumor necrosis factor (TNF) receptor and Fas/APO1 induce cell death via distinct regions in their intracellular domains. Three cytoplasmic proteins that bind to these receptor regions have been identified recently. One, MORT1 (also called FADD), binds to Fas/APO1 but not to p55-R; another, TRADD, binds to the p55 TNF receptor but not to Fas/APO1; and the third, RIP, binds weakly to both receptors. The regions within these proteins that are involved in binding to the receptors and the receptor regions to which they bind share a common sequence motif, that of the "death domain." This study shows that the death domain motifs in MORT1, TRADD, and RIP bind effectively to each other, a mode of binding that may allow "cross-talk" between the functional expression of the p55 TNF receptor and Fas/APO1.
WT1: a weak spot in KRAS-induced transformation
Authors: Silvia Licciulli, Joseph L. Kissil
Journal: Journal of Clinical Investigation (2010)

Activating mutations in the Ras alleles are found frequently in tumors, making the proteins they encode highly attractive candidate therapeutic targets. However, Ras proteins have proven difficult to target directly. Recent approaches have therefore focused on identifying indirect targets to inhibit Ras-induced oncogenesis. For example, RNAi-based negative selection screens to identify genes that when silenced in concert with activating Ras mutations are incompatible with cellular proliferation, a concept known as synthetic lethality. In this issue of the JCI, Vicent et al. report on the identification of Wilms tumor 1 (Wt1) as a Kras synthetic-lethal gene in a mouse model of lung adenocarcinoma. Silencing of Wt1 in cells expressing an endogenous allele of activated Kras triggers senescence in vitro and has an impact on tumor progression in vivo. These findings are of significant interest given previous studies suggesting that the ability of oncogenic Kras to induce senescence versus proliferation depends on its levels of expression.
Dysphagia with a thyroid nodule: is there a primary aerodigestive malignancy?
Authors: Konstantinos Michalopoulos, Sinnappa Gunasekaran, James W Moor, Chris Bem
Journal: Journal of the Royal Society of Medicine (2008)

Summary Three cases of laryngopharyngeal primary squamous cell carcinoma presenting with thyroid nodules are described. The key message to take away from these cases is that patients with advanced malignancy of the upper aerodigestive tract can present with a thyroid nodule.
MPs criticise government for taking MRC money needed for new research centre
Authors: Susan Mayor
Journal: BMJ (2008)

English MPs have challenged the government to explain why it has taken money from the Medical Research Council (MRC) that was expected to go towards funding a new medical research centre.

The MPs raised the matter during a recent meeting of the House of Commons Innovation, Universities, and Skills Committee to review plans for the UK Centre for Medical Research and Innovation, which will be located in central London.

The centre, announced in December 2007, will bring together research teams from the MRC’s National Institute for Medical Research, the Cancer Research UK London Research Institute, and University College London. The Wellcome Trust will also fund scientists working at the centre, which is planned to open in …
Cardiac Valvular Replacement: Role of the Aortic Homograft
Authors: W W Angell, N E Shumway
Journal: Annual Review of Medicine (1968)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Clonal Isolation of Different Strains of Mouse Mammary Tumor Virus-Like DNA Sequences from Both the Breast Tumors and Non-Hodgkin’s Lymphomas of Individual Patients Diagnosed with Both Malignancies
Authors: Polly R. Etkind, Alexandre F. R. Stewart, Thambi Dorai, Daniel J. Purcell, Peter H. Wiernik
Journal: Clinical Cancer Research (2004)

Abstract Purpose: In a previous study, we had detected the presence of mouse mammary tumor virus (MMTV)-like envelope (ENV) gene sequences in both the breast tumors and non-Hodgkin’s lymphoma tissue of two of our breast tumor patients who had been diagnosed simultaneously with both malignancies. The aim of this study was to determine if MMTV-like DNA sequences are present in the breast tumors and non-Hodgkin’s lymphomas of additional patients suffering from both malignancies and if so to characterize these sequences in detail. Experimental Design: DNA was extracted from formalin-fixed, paraffin-embedded tissue sample blocks of breast tumors and non-Hodgkin’s lymphomas from patients suffering from both malignancies. A 250-bp region of the MMTV ENV gene and a 630-bp region of the MMTV long terminal repeat (LTR) open reading frame (ORF) that encodes the MMTV superantigen (sag) gene were amplified by PCR from the isolated DNA. Amplified products were analyzed by Southern blotting, cloned, and sequenced. Results: MMTV-like ENV and LTR sequences were detected in both the breast tumors and non-Hodgkin’s lymphomas of 6 of 12 patients suffering from both malignancies. A novel mutant of the MMTV ENV gene was identified in these patients. Characterization of the MMTV-like LTR highly variable sag sequences revealed total or nearly total identity to three distinct MMTV proviruses from two different branches of the MMTV phylogenetic tree. Conclusions: The presence of MMTV-like ENV and LTR sequences in both the breast tumors and non-Hodgkin’s lymphomas of 6 additional patients suggests a possible involvement of these sequences in these two malignancies. MMTV-like LTR sequence homology to different MMTV proviruses revealed the presence of more than one strain of MMTV-like sequences in each individual suggesting the possibility of multiple infections in these patients.
A Randomized Trial of Nighttime Physician Staffing in an Intensive Care Unit
Authors: Meeta Prasad Kerlin, Dylan S. Small, Elizabeth Cooney, Barry D. Fuchs, Lisa M. Bellini, Mark E. Mikkelsen, William D. Schweickert, Rita N. Bakhru, Nicole B. Gabler, Michael O. Harhay, John Hansen-Flaschen, Scott D. Halpern
Journal: New England Journal of Medicine (2013)

Increasing numbers of intensive care units (ICUs) are adopting the practice of nighttime intensivist staffing despite the lack of experimental evidence of its effectiveness.
Abstract 3719: xCT inhibition suppresses CD44v-positive stem-like tumor cells, which are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma.
Authors: Momoko Yoshitake, Osamu Nagano, Taneaki Nakagawa, Hideyuki Saya
Journal: Cancer Research (2013)

Abstract Given that cancer cells are exposed to environmental stressors such as oxygen or nutrient deficiency, low pH, inflammatory mediators, and ROS during tumor progression,the ability to avoid the consequences of such exposure is required for cancer cell survival. CD44 is a major marker for stem-like cancer cells in many epithelial tumors and has been implicated in tumor growth, invasion, and metastasis. CD44 exists in numerous variant isoforms (CD44v) that are generated through alternative mRNA splicing. We recently showed that interaction of CD44v with the cystine transporter subunit xCT stabilizes the latter protein and thereby potentiates the ability of cancer cells to defend themselves against reactive oxygen species (ROS). Stem-like cancer cells in which defense against ROS is enhanced by CD44v are thus thought to drive tumor growth, chemoresistance and metastasis. In the present study, we show that head and neck squamous cell carcinoma (HNSCC) cells that express CD44v rely on the activity of the cystine transporter subunit xCT for control of their redox status. Ablation of CD44v attenuated the xCT dependency as well as tumor-forming ability in HNSCC cells, and xCT inhibition selectively induced apoptosis in CD44v-expressing tumor cells. In contrast, CD44v-negative differentiated cells manifest epidermal growth factor receptor (EGFR) activation and rely largely on EGFR activity for their survival. Combined treatment with inhibitors of xCT-dependent cystine transport and of EGFR may induce apoptosis in distinct subpopulations of HNSCC tumor cells. Citation Format: Momoko Yoshitake, Osamu Nagano, Taneaki Nakagawa, Hideyuki Saya. xCT inhibition suppresses CD44v-positive stem-like tumor cells, which are resistant to EGFR-targeted therapy in head and neck squamous cell carcinoma. [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 3719. doi:10.1158/1538-7445.AM2013-3719
Breast Cancer Cells Can Evade Apoptosis-Mediated Selective Killing by a Novel Small Molecule Inhibitor of Bcl-2
Authors: Pedro Jose Real, Yeyu Cao, Renxiao Wang, Zaneta Nikolovska-Coleska, Jaime Sanz-Ortiz, Shaomeng Wang, Jose Luis Fernandez-Luna
Journal: Cancer Research (2004)

Abstract Proteins of the Bcl-2 family are key regulators of caspase activation and apoptosis. Some members of this family, notably Bcl-2 and Bcl-xL, are overexpressed in cancer cells, which have been associated with chemoresistance. We have designed and synthesized a small molecule inhibitor of Bcl-2, named YC137, and studied its role in cancer cells. In vitro studies showed that YC137 inhibits the binding of the Bid BH3 peptide to Bcl-2, thus disrupting an interaction essential for the antiapoptotic activity of Bcl-2. This inhibitor induces apoptosis of hematopoietic progenitors overexpressing Bcl-2 but not Bcl-xL and breast cancer cells that express high levels of Bcl-2. On the contrary, a variety of normal primary cells, including CD34+ progenitors, myoblasts, and peripheral blood mononuclear cells, do not respond to the inhibitor. A breast cancer cell line resistant to YC137 was generated. Analysis of resistant cells revealed a reduced expression of Bcl-2, which correlated with low activation of signal transducer and activator of transcription-3 (Stat3) and reduced expression of the human epidermal growth factor receptor-2 (HER2). Of note, YC137-resistant cells were more sensitive to apoptosis induced by chemotherapy. Because HER2 has not been linked previously to the Stat3-Bcl-2 transcriptional pathway, we additionally confirmed that specific blockade of HER2 in breast cancer cells resulted in down-regulation of Stat3 activity and reduced levels of Bcl-2. Consistently, HER2 blockade led to YC137 resistance. These data provide evidence for the selective killing of tumor cells by YC137 and represent the first example of in vitro selection of cancer cells refractory to a Bcl-2 inhibitor.