tbuckley/cabot-search huggingface dataset:
Blood Glucose Levels in Malawian Children before and during the Administration of Intravenous Quinine for Severe falciparum Malaria
Authors: Terrie E. Taylor, Malcolm E. Molyneux, Jack J. Wirima, K. Alex Fletcher, Keith Morris
Journal: New England Journal of Medicine (1988)

Hypoglycemia may develop in patients with severe untreated malaria and can complicate the course of treatment with parenteral quinine as a result of quinine-induced hyperinsulinemia. Intravenous quinine is used increasingly as the therapy of choice in patients with severe malaria, most of whom are children. To assess the importance of both pretreatment and quinine-related hypoglycemia in children in an area in which the disease is endemic, we prospectively studied 95 Malawian children with falciparum malaria and altered consciousness who were treated with intravenous quinine. Nineteen patients had hypoglycemia before treatment. Seven (37 percent) died, and five of the survivors (26 percent) had neurologic sequelae. The corresponding values for patients who were initially normoglycemic were 4 percent and 4 percent, respectively (P<0.0001). Hypoglycemia was associated with low plasma insulin concentrations and with elevated plasma concentrations of lactate, alanine, and 5′-nucleotidase — a finding that suggests that impaired hepatic gluconeogenesis but not hyperinsulinemia contributes to the pathogenesis of pretreatment hypoglycemia. All patients were given quinine dihydrochloride in a 5 percent dextrose infusion, and those with hypoglycemia received 50 percent dextrose. Hypoglycemia recurred in seven of the patients with pretreatment hypoglycemia, but these episodes were also not associated with hyperinsulinemia. Of the 76 children who were initially normoglycemic, none became hypoglycemic during the course of treatment with intravenous quinine. We conclude that hypoglycemia is a frequent complication of falciparum malaria in children and that it reflects severe disease and is associated with a poor prognosis. We did not find it to be a complication of quinine treatment. (N Engl J Med 1988; 319:1040–7.)
Comprehensive Minority Biomedical Program Encourages Involvement in Cancer Research
Authors: K. Ruddon
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Comprehensive Minority Biomedical Program Encourages Involvement in Cancer Research Get access Kate Ruddon Kate Ruddon Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 16, 19 October 1988, Pages 1272–1275, https://doi.org/10.1093/jnci/80.16.1272-a Published: 19 October 1988
Reduced Hepatic Uptake of Tc-99m Stannous Colloid–Labeled Leukocytes in a Patient with Congenital Hepatic Fibrosis and Alcoholic Liver Disease
Authors: CHONG G. CHEW, DYLAN BARTHOLOMEUSZ, BARRY CHATTERTON
Journal: Clinical Nuclear Medicine (2000)

A 43-year-old man with liver failure caused by alcohol abuse and congenital hepatic fibrosis was examined for intermittent fever of unknown origin. He had portal hypertension, which was complicated in the past by bleeding varices that required a portocaval shunt. There were no localizing symptoms or signs for the fever, and, apart from an elevated leukocyte count, results of investigations including urine and blood cultures, abdominal ultrasound, abdominal magnetic resonance imaging, and endoscopic retrograde cholangiopancreatography were not helpful. A labeled leukocyte scan was obtained with Tc-99m stannous colloid. The 1-, 3-, and 24-hour images showed marked reduction in tracer uptake within the liver, with increased tracer accumulation in an enlarged spleen and marrow. Marked margination of labeled leukocytes in the lungs was also evident, which subsided on the 24-hour image. The focus of inflammation was not identified, and instead the tracer distribution pattern was similar to that on a Tc-99m sulfur colloid scan in a patient with liver failure. The scan appearances presumably represent reduced uptake of free Tc-99m stannous colloid by Kuppfer cells of the failing liver, with a shift in uptake to the reticuloendothelial system of the spleen and marrow.
Reply to Cipoletta et al.
Authors: N. Yoshida, N. Yagi, Y. Naito
Journal: Endoscopy (2010)

We have read the letter by Cipoletta et al. suggesting the use of the unified term “endoscopic resection.” We thank the authors for their concern about our previous publication in Endoscopy [1]. In our previous report, we applied the term “endoscopic submucosal dissection (ESD)” to our method. Recently, the term ESD has been used frequently and internationally [1] [2] [3]; the term “mucosectomy” had been previously used [4]. The term ESD was used to describe a specific type of endoscopic mucosal resection (EMR) because it was thought to be an improved technique of EMR [5]. The proliferation of different definitions has generated some confusion, as Cipoletta et al. have indicated. However, we think the introduction of ESD has been the main cause of this confusion. In addition, there is a significant difference in the rate of en bloc resection between the two methods, which may affect the accuracy of the histological diagnosis. In Japan, the term ESD is already commonly used by our professional and academic institutions [1] [2].
Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma
Authors: Jan C. Buckner, Edward G. Shaw, Stephanie L. Pugh, Arnab Chakravarti, Mark R. Gilbert, Geoffrey R. Barger, Stephen Coons, Peter Ricci, Dennis Bullard, Paul D. Brown, Keith Stelzer, David Brachman, John H. Suh, Christopher J. Schultz, Jean-Paul Bahary, Barbara J. Fisher, Harold Kim, Albert D. Murtha, Erica H. Bell, Minhee Won, Minesh P. Mehta, Walter J. Curran
Journal: New England Journal of Medicine (2016)

Grade 2 gliomas occur most commonly in young adults and cause progressive neurologic deterioration and premature death. Early results of this trial showed that treatment with procarbazine, lomustine (also called CCNU), and vincristine after radiation therapy at the time of initial diagnosis resulted in longer progression-free survival, but not overall survival, than radiation therapy alone. We now report the long-term results.We included patients with grade 2 astrocytoma, oligoastrocytoma, or oligodendroglioma who were younger than 40 years of age and had undergone subtotal resection or biopsy or who were 40 years of age or older and had undergone biopsy or resection of any of the tumor. Patients were stratified according to age, histologic findings, Karnofsky performance-status score, and presence or absence of contrast enhancement on preoperative images. Patients were randomly assigned to radiation therapy alone or to radiation therapy followed by six cycles of combination chemotherapy.A total of 251 eligible patients were enrolled from 1998 through 2002. The median follow-up was 11.9 years; 55% of the patients died. Patients who received radiation therapy plus chemotherapy had longer median overall survival than did those who received radiation therapy alone (13.3 vs. 7.8 years; hazard ratio for death, 0.59; P=0.003). The rate of progression-free survival at 10 years was 51% in the group that received radiation therapy plus chemotherapy versus 21% in the group that received radiation therapy alone; the corresponding rates of overall survival at 10 years were 60% and 40%. A Cox model identified receipt of radiation therapy plus chemotherapy and histologic findings of oligodendroglioma as favorable prognostic variables for both progression-free and overall survival.In a cohort of patients with grade 2 glioma who were younger than 40 years of age and had undergone subtotal tumor resection or who were 40 years of age or older, progression-free survival and overall survival were longer among those who received combination chemotherapy in addition to radiation therapy than among those who received radiation therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00003375.).
Lysyl Oxidase (LOX) Transcriptionally Regulates <i>SNAI2</i> Expression and TIMP4 Secretion in Human Cancers
Authors: Myriem Boufraqech, Lisa Zhang, Naris Nilubol, Samira M. Sadowski, Shweta Kotian, Martha Quezado, Electron Kebebew
Journal: Clinical Cancer Research (2016)

Epithelial-to-mesenchymal transition (EMT) is important in cancer progression and metastasis. We and others have previously reported that lysyl oxidase (LOX) is overexpressed in aggressive cancers, is associated with increased mortality, and regulates EMT. However, the mechanism by which LOX mediates EMT is unknown. In this study, we investigated the effect of LOX on mediators of EMT.We used chromatin immunoprecipitation and promoter luciferase assays to determine the target gene of LOX. To determine the effects of SNAI2 in vivo, we used our metastatic anaplastic thyroid cancer (ATC) mouse model. To investigate the effects of LOX and SNAI2 on MMPs and TIMPs, protein arrays were used. Primary tumors from patients with metastatic, breast and colon cancer, and tissue array for thyroid cancer were assessed for SNAI2 and TIMP4 expression by immunohistochemistry.We found that LOX knockdown decreases SNAI2 expression in cancer cell lines. Furthermore, knockdown of LOX reduced SNAI2 expression in a metastatic mouse model of thyroid cancer. We also demonstrated that LOX binds and transactivates the SNAI2 promoter. We found a direct correlation in thyroid and breast cancer samples between LOX and SNAI2 expression. To understand how LOX/SNAI2 axis mediates these effects, we performed a comprehensive analysis of MMPs/TIMPs. LOX and SNAI2 depletion reduced TIMP4 secretion. Analysis of SNAI2 and TIMP4 expression showed overexpression of both proteins in aggressive thyroid, colon, and breast tumors.Our findings provide new evidence that LOX regulates SNAI2 expression and that SNAI2-mediated TIMP4 secretion plays a role in cancer progression. Clin Cancer Res; 22(17); 4491-504. ©2016 AACR.
Bone Imaging of Sternal Metastasis from Hepatocellular Carcinoma with Disease Progression
Authors: Seok Tae Lim, Myung-Hee Sohn, Jae-Yong Kwak, Chang-Yeol Yim
Journal: Clinical Nuclear Medicine (2002)

TAE LIM, SEOK M.D.*‡§; SOHN, MYUNG-HEE M.D.*‡§; KWAK, JAE-YONG M.D.†‡§; YIM, CHANG-YEOL M.D.†‡§ Author Information
A case of cervical esophageal perforation after transnasal gastrointestinal fibroscopy using a small-caliber fiber
Authors: Y. Moriwaki, S. Arata, M. Iwashita, H. Toyoda, T. Kosuge, N. Suzuki
Journal: Endoscopy (2011)

Transnasal gastrointestinal fibroscopy using a small-caliber fiberscope (N-GIF) has been established as a safe procedure because it can prevent undesired pharyngeal reflux [1] [2]. However, the risks and complications related to N-GIF remain unclear [1] [2] [3] [4] [5].
Spleen Inferior to the Liver
Authors: LÁSZLÓ GALUSKA
Journal: Clinical Nuclear Medicine (2000)

A 52-year-old woman with intermittent pain in the right upper abdominal area was sent to our nuclear medical department to characterize the nature of an ultrasonographically visualized tumor, persisting below the right lobe of the liver. Tc-99m sulfur colloid planar gamma camera scintigraphy revealed a 6-cm spherical accumulation inferior to the right liver lobe and a smaller one posterior to the liver. Other nuclear medical studies indicated that this was the spleen. This was a single developmental disorder, without abnormalities of other abdominal organs.
Abstract 1633: C-terminal binding proteins are novel drug targets
Authors: Michael W. Straza, Ramesh C. Kovi, Seema Paliwal, Barur Rajeshkumar, Brendan Hilbert, Tyler Doughty, Daniel Parker, William Royer, Giles F. Whalen, Stephen Lyle, Celia A. Schiffer, Steven R. Grossman
Journal: Cancer Research (2011)

Abstract The CtBP transcriptional corepressors have been identified as proto-oncogenes. CtBP represses pro-apoptotic genes and promotes cancer cell migration and invasion in a redox sensitive manner through a regulatory dehydrogenase domain. The CtBP dehydrogenase substrate 4-methylthio-2-oxobutyric acid (MTOB) can act as a CtBP inhibitor at high concentrations, and induces apoptosis in the human colorectal cancer cell line HCT116. MTOB induced apoptosis is dependent upon expression of the BH3 only protein BIK, a previously established CtBP target. Treatment of both native and transformed Mouse Embryonic Fibroblasts revealed a wide therapeutic index for CtBP inhibition. In human colon cancer cell peritoneal xenografts, MTOB treatment reduced tumor growth and induced apoptosis in vivo without notable toxicity. To verify the potential utility of CtBP as a therapeutic target in human cancer, the expression of CtBP and its negative regulator ARF was studied in a series of resected human colon adenocarcinomas. CtBP and ARF levels were inversely-correlated, with elevated CtBP levels (compared with adjacent normal tissue) observed in greater than 60% of specimens, with ARF absent in nearly all specimens exhibiting elevated CtBP levels. Thus, CtBP is a viable therapeutic target in human cancer. In order to identify novel CtBP inhibitors, a simple dehydrogenase assay was developed that utilizes the spectrophotometric measurement of enzymatic conversion of NADH to NAD+ by the CtBP dehydrogenase activity. This assay successfully detects MTOB substrate and inhibitor activity, as well as inhibition of CtBP activity by the related compound 4-methylthio-2-hydroxybutyric acid (MTHB). This assay will be adapted for high throughput screening of small molecule libraries for novel CtBP inhibitors that can be further characterized in pre-clinical models. 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 1633. doi:10.1158/1538-7445.AM2011-1633
752 THERAPEUTIC VACCINATION FOR CHRONIC HEPATITIS B (CHB) USING HETEROLOGOUS PROTEIN PRIME/VECTOR BOOST VACCINATION SCHEME
Authors: C. Jäger, M. Ringelhan, C. Dembek, S. Backes, M. Heikenwälder, G. Mutwiri, L. Babiuk, U. Protzer
Journal: Journal of Hepatology (2013)
Abstract LB-33: TRPV1 suppresses intestinal tumorigenesis by negatively regulating EGFR signaling.
Authors: Petrus R. de Jong, Naoki Takahashi, Alexandra R. Harris, Jihyung Lee, Samuel Bertin, Eyal Raz
Journal: Cancer Research (2013)

Abstract The intestinal epithelium is the most rapidly self-renewing tissue. This dynamic process is mainly driven by Wnt, Notch and EGFR signaling in the crypts of Lieberkühn. These signaling pathways are negatively regulated by multiple control mechanisms to restrain intestinal epithelial cell (IEC) turnover and thereby reduce the risk of oncogenic transformation. Here we report a novel homeostatic feedback loop, intrinsic to IEC, between the EGFR and a member of the transient receptor potential (TRP) ion channel family. We identified that TRP vanilloid 1 (TRPV1), a polymodal pain receptor, is expressed by IEC and that this channel negatively regulates EGFR-induced cell proliferation in vivo. Intestinal crypt cultures (organoids) from Trpv1-/- mice showed hyperproliferation, crypt elongation and a reduced requirement for exogenous EGF compared to WT controls. Importantly, genetic deletion of Trpv1 increased the intestinal tumor load in multiple intestinal neoplasia (Apc+/min) mice, which was reversed by EGFR kinase inhibitor treatment. Continuous oral administration of a dietary TRPV1 agonist, capsaicin, suppressed intestinal tumorigenesis in Apc+/min mice in a TRPV1-dependent manner. In addition we found that capsaicin worked synergistically with a COX2 inhibitor, celecoxib, in the prevention of intestinal neoplasia development in these mice. Mechanistically, we show that TRPV1 is activated by EGFR signaling through phospholipase C (PLC). TRPV1 signaling subsequently restrains EGFR signaling through Ca2+-dependent triggering of protein tyrosine phosphatase (PTP) activity. Together, these findings suggest an intrinsic mechanism that exerts negative feedback on EGFR signaling through Ca2+ channel TRPV1 that thereby acts as a tumor suppressor in the intestinal epithelium. Citation Format: Petrus R. de Jong, Naoki Takahashi, Alexandra R. Harris, Jihyung Lee, Samuel Bertin, Eyal Raz. TRPV1 suppresses intestinal tumorigenesis by negatively regulating EGFR signaling. [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-33. doi:10.1158/1538-7445.AM2013-LB-33
Regulation of pathogenic effector/memory T helper 1 lymphocyte survival by microRNA
Authors: Claudia Haftmann, Anna-Barbara Stittrich, Gitta Heinz, Zhuo Fang, Nikolaus Rajewsky, Hyun-Dong Chang, Andreas Radbruch, Mir-Farzin Mashreghi
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Backgroundand objectives</h3> Auto-antigen specific effector memory T helper type 1 lymphocytes (Th1) are critically involved in the development and maintenance of chronic inflammation in autoimmune diseases. These cells reside at inflamed tissues, function independently of antigenic stimulation and proliferation, and therefore are resistant against physiological regulation and conventional immunosuppressive therapies. The acquirement of these properties is probably mediated by reduced expression of the pro-apoptotic proteins BIM and Pten. Recent results suggest that microRNA (miRNA) mediated regulation of <i>BIM</i> and <i>Pten</i> may play an important role for the development, function and persistence of chronically activated effector memory Th1 cells in autoimmune disease. Therefore, the authors aimed to identify miRNAs with the ability to suppress the expression of <i>BIM</i> and <i>Pten</i> in such cells. <h3>Material and methods</h3> Assuming that Th1 cells involved in autoimmune inflammation have a history of repeated restimulation by persistent (auto) antigens, the authors have in vitro generated acutely (once) activated and chronically (four times) activated murine memory/effector Th1 cells. By using high-throughput sequencing of miRNA expression libraries, the authors have identified miRNAs differentially expressed between once and repeatedly reactivated Th1 cells. The functional role of specific candidate miRNAs in mediating the persistence of chronically activated effector memory Th1 cells was examined by loss- and gain of function experiments. <h3>Results</h3> The authors have identified a candidate miRNA, specifically induced in chronically activated effector/memory Th1 cells. This miRNA post-transcriptionally inhibits the pro-apoptotic genes <i>Bim</i> and <i>Pten</i>. Expression of both genes is reduced in chronically activated memory effector Th1 cells. Overexpression of this miRNA in activated Th1 cells results in 50% downregulation of endogenous <i>Bim</i> and <i>Pten</i> expression. Conversely, inhibition of the candidate miRNA in chronically activated memory Th1 cells by antagomirs results in induced levels of BIM protein and significantly enhanced cell death. Under Th1 polarising conditions, the expression of the candidate miRNA is regulated by the master transcription factor Tbet. <h3>Conclusions</h3> With its targets BIM and Pten having important roles for survival and proliferation of pathogenic effector memory Th1 cells, this candidate miRNA represents a promising molecular target for the treatment of immune mediated disease by antagomirs.
GENDER AND RACE DIFFERENCES IN AGING-RELATED ALTERATION IN MYOCARDIAL SYSTOLIC FUNCTION ASSESSED BY 2D SPECKLE TRACKING ECHOCARDIOGRAPHY OVER A 20 YEAR FOLLOW-UP: THE CARDIA STUDY
Authors: Chike Nwabuo, Eui-Young Choi, Bharath Ambale Venkatesh, Satoru Kishi, Andre L. Almeida, Henrique T. Moreira, Ravi Sharma, Anderson C. Armstrong, Gisela Teixido, Ola Gjesdal, Cora Lewis, Stephen Sidney, Samuel Gidding, Joao Lima
Journal: Journal of the American College of Cardiology (2015)
Cellular mechanisms of long-term depression: From consensus to open questions
Authors: F. Crépel
Journal: Behavioral and Brain Sciences (1996)

The target article on cellular mechanisms of long-term depression appears to have been well received by most authors of the relevant commentaries. This may be due to the fact that this review aimed to give a general account of the topic, rather than just describe previous work of the present author. The present response accordingly only raises questions of major interest for future research.
Genetic Disorders of Renal Electrolyte Transport
Authors: Steven J. Scheinman, Lisa M. Guay-Woodford, Rajesh V. Thakker, David G. Warnock
Journal: New England Journal of Medicine (1999)

In the 1950s and 1960s, several inherited disorders of fluid and electrolyte metabolism were described in which the principal disturbance appeared to be a specific functional defect in the renal tubule. For most of these diseases, plausible physiologic explanations were presented, some more convincing than others. In the past five years, genetic and molecular approaches have elucidated the underlying molecular defects in several of these disorders. In some instances, predictions based on the initial physiologic studies have been confirmed; in others, the molecular answer has come as a surprise, raising further questions about the physiology of epithelial function. In several . . .