tbuckley/cabot-search huggingface dataset:
Oncolysis of Multifocal Hepatocellular Carcinoma in the Rat Liver by Hepatic Artery Infusion of Vesicular Stomatitis Virus
Authors: Katsunori Shinozaki, Oliver Ebert, Chryssanthi Kournioti, Yun-Sheng Tai, Savio L.C Woo
Journal: Molecular Therapy (2004)

Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and few effective treatments, as well as ever-increasing frequencies in the Western world. Viruses that replicate selectively in cancer cells hold considerable promise as novel therapeutic agents for the treatment of malignancy. Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with intrinsic oncolytic specificity due to significantly attenuated antiviral responses in many tumor cells. The aim of this study was to evaluate the potential of VSV, administered via the hepatic artery, as an effective and safe therapeutic agent for treating "multifocal" HCC in the rat liver. Recombinant VSV vector expressing beta-galactosidase (rVSV-beta-gal) was generated by reverse genetics and infused into the hepatic artery of Buffalo rats bearing orthotopically implanted multifocal HCC. Access by the virus to multifocal HCC lesions in the liver, as well as the kinetic profiles of intratumoral viral replication and spread, was established by X-gal staining of liver and tumor sections. Plaque assays were also performed to determine the infectious viral yields in tumor and normal liver tissues. Pharmacotoxicology studies, including serum chemistries and proinflammatory cytokine production, as well as organ histopathology, were performed. Buffer- or vector-treated tumor-bearing rats were followed for survival and the results were analyzed by the Kaplan-Meier method and the log-rank test. Hepatic arterial infusion of rVSV-beta-gal at the maximum tolerated dose in tumor-bearing rats resulted in efficient viral transduction of multifocal HCC lesions in their livers, tumor-selective viral replication, and extensive oncolysis. Importantly, no significant vector-associated toxicities were noted and, in particular, no damage to the hepatic parenchyma was seen. Finally, survival of vector-treated rats was substantially prolonged over that of animals in the control treatment group (p < 0.028). Thus, hepatic arterial administration of VSV is both effective and safe in an orthotopic animal model of multifocal HCC. The results suggest that oncolytic VSV can be developed into an effective and safe therapeutic modality for patients with multifocal HCC in the future.
Physical Diagnosis: Bedside Evaluation of Diagnosis and Function
Authors: Virginia U. Collier
Journal: JAMA (1995)

<i>Physical Diagnosis: Bedside Evaluation of Diagnosis and Function</i>was written on the premise that "the human interaction of diagnostician and subject, of healer and patient, must not be undermined by inadequate preparation of the early learner or incomplete maintenance of skills by the experienced clinician." Its goal is to present sequential teaching of interviewing and physical diagnosis skills for both fledgling and experienced clinicians. After an initial chapter on general concepts of the medical history and physical examination, the majority of the chapters deal with anatomic regions. For each area (skin, head, eyes, ears, nose, oral cavity and throat, neck, breasts, etc), there is a section on the screening examination for the novice and another on the extended examination "to provide, for the more advanced clinician, a reference source for special
Increases in kidney volume in autosomal dominant polycystic kidney disease can be detected within 6 months
Authors: Andreas D. Kistler, Diane Poster, Fabienne Krauer, Dominik Weishaupt, Shagun Raina, Oliver Senn, Isabelle Binet, Katharina Spanaus, Rudolf P. Wüthrich, Andreas L. Serra
Journal: Kidney International (2008)
Smoking, alcohol and life events related to psoriasis among women
Authors: K. POIKOLAINEN, T. REUNALA, J. KARVONEN
Journal: British Journal of Dermatology (1994)

Journal Article Smoking, alcohol and life events related to psoriasis among women Get access K. POIKOLAINEN, K. POIKOLAINEN National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar T. REUNALA, T. REUNALA Department of Dermatology, University of Helsinki, 00250 Helsinki, Finland Search for other works by this author on: Oxford Academic Google Scholar J. KARVONEN J. KARVONEN Department of Dermatology, Oulu University Hospital, 90220 Oulu, Finland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 4, 1 April 1994, Pages 473–477, https://doi.org/10.1111/j.1365-2133.1994.tb03380.x Published: 01 April 1994 Article history Accepted: 25 October 1993 Published: 01 April 1994
Rate of acetylcholine hydrolysis affects the phase dependency of cardiac responses to vagal stimulation
Authors: R. J HENNING, Y. MASUDA, T. YANG, M. N LEVY
Journal: Cardiovascular Research (1987)

Journal Article Rate of acetylcholine hydrolysis affects the phase dependency of cardiac responses to vagal stimulation Get access ROBERT J HENNING, ROBERT J HENNING From the Department of Investigative Medicine, Mount Sinai Medical Center, Case Western Reserve University, Cleveland, Ohio, USA Address for correspondence and reprints: Dr Matthew N Levy, Department of Investigative Medicine, Mt Sinai Medical Center, 1 Mt Sinai Drive, Cleveland, Ohio 44106, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar YUKITAKA MASUDA, YUKITAKA MASUDA From the Department of Investigative Medicine, Mount Sinai Medical Center, Case Western Reserve University, Cleveland, Ohio, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar TIANEN YANG, TIANEN YANG From the Department of Investigative Medicine, Mount Sinai Medical Center, Case Western Reserve University, Cleveland, Ohio, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar MATTHEW N LEVY MATTHEW N LEVY From the Department of Investigative Medicine, Mount Sinai Medical Center, Case Western Reserve University, Cleveland, Ohio, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 21, Issue 3, March 1987, Pages 169–176, https://doi.org/10.1093/cvr/21.3.169 Published: 01 March 1987 Article history Received: 13 December 1985 Accepted: 10 July 1986 Published: 01 March 1987
Gastric Necrosis Due to Prolonged Local Gastric Hypothermia
Authors: Joseph R. Cali
Journal: JAMA (1965)

SINCE THE original observations made by Wangensteen et al 1 in 1958 on the effect of gastric freezing and hypothermia on gastric secretion, considerable clinical experience has been obtained with these two modalities of therapy.  Gastric freezing has been used widely in the treatment of duodenal ulcers, with varying results. 2,3 Inflow temperatures have varied from —10 C to —20 C, and freezing has been carried out for 45 minutes to one hour. Numerous complications, such as gastric ulcers and varying degrees of gastric necrosis, have been reported 4 and are considered directly attributable to the low temperatures employed.  In contrast, gastric hypothermia has been used in the management of massive upper gastro intestinal hemorrhage with very promising results. 5-7 The inflow temperatures used in this latter modality have varied between +2 C to +6 C for periods averaging approximately 48 hours.  Since Jan 1, 1963, a program using gastric
Double-blind crossover comparison of enoximone and placebo in patients with congestive heart failure.
Authors: S K Choraria, D Taylor, J Pilcher
Journal: Circulation (1987)

The efficacy of oral enoximone, a new positive inotropic and vasodilator agent, was assessed in 12 patients with chronic congestive heart failure (New York Heart Association [NYHA] class II or III) in a double-blind randomized crossover comparison with placebo. Duration of each treatment was 6 weeks and the dose of enoximone was 150 mg tid. Efficacy was assessed by exercise tolerance, symptoms, radionuclide angiography for ejection fraction at rest and during exercise, and Holter monitoring. Two patients were withdrawn before completion of the study, one with pulmonary edema after 1 week on placebo and the other for noncompliance with enoximone therapy. Symptom-limited exercise capacity improved with enoximone by 30% and 43% (p less than .01) compared with baseline after 2 and 6 weeks treatment, respectively. Ejection fraction improved at rest (p less than .02) with enoximone but not with placebo. No change was found during exercise. Heart rate and blood pressure remained unaltered. During treatment with enoximone symptoms of exertional dyspnea and fatigue were improved and NYHA class decreased by at least one class for every patient. Holter monitoring revealed an overall increase (NS) in ectopic activity during enoximone therapy. There were no serious adverse effects and laboratory values did not change significantly. The addition of enoximone to the existing therapy of patients with moderately severe congestive heart failure provided clear and sustained subjective and objective benefit when compared with placebo.
Studies of Blood Coagulation and Fibrinolysis in Patients with Idiopathic Hyperlipemia and Primary Hypercholesteremia before and after a Fatty Meal
Authors: SAUL I. NITZBERG, M. ANTHONY PEYMAN, ROBERT GOLDSTEIN, SAMUEL PROGER
Journal: Circulation (1959)

In view of the current interest in the possible relationship between elevated serum lipid levels, increased coagulability of the blood (or decreased blood fibrinolysis) and ischemic heart disease, the clotting and fibrinolytic activity of the blood were studied before and after a fatty meal in 9 patients with idiopathic hyperlipemia, 10 patients with primary hypercholesteremia, and 10 normal subjects. Six patients had evidence of coronary heart disease. The methods of study included procedures designed to assess the over-all coagulability of the blood as well as the measurement of specific clotting factors. Blood fibrinolytic activity was measured by both direct and indirect methods. Serum lipid studies were performed simultaneously.
Abstract 2242: The MAPK and PI3K signaling pathways in breast cancer: Crosstalk mechanisms and the effect on cell proliferation
Authors: Darlene A. Monlish, Jane E. Cavanaugh
Journal: Cancer Research (2012)

Abstract The purpose of the current study is to assess crosstalk between the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K) pathways in breast cancer. More specifically, the goal is to investigate the interaction between the extracellular signal regulated kinases 1/2 and 5 (ERK1/2 and ERK5) and Akt and how these kinases act in concert to promote sustained proliferation in a breast cancer model. The MAPK and PI3K pathways mediate numerous cellular processes, including differentiation, growth, proliferation, and survival. To date, most related studies have focused on assessment of the crosstalk mechanisms between ERK1/2 and Akt, while the interplay of ERK5 has remained largely unstudied. Breast cancer patients with increased levels of ERK5 have been found to have a poorer prognosis than patients with lower levels, warranting further investigation of this kinase. The interaction between ERK5 and ERK1/2, as well as between ERK5 and Akt, and how these signaling mechanisms act in conjunction to promote cell proliferation in breast cancer cells remains to be elucidated. The BT-474 (ER+/PR+/HER2+) and MDA-MB-231 (ER-/PR-/HER2-) human breast cancer cell lines were utilized to examine ERK1/2, ERK5 and Akt activation following treatment with ERK and Akt inhibitors or siRNA for these kinases, respectively. Western blot analysis was performed to determine expression and activation of the kinases. An MTT assay was used to assess changes in cell proliferation following kinase inhibition for 12, 24, 48, 72 and 96 hours. In vivo studies utilizing the transgenic MMTV-neu mouse model were also performed. In the BT-474 cell line, inhibition of Akt resulted in increased ERK1/2 and ERK5 expression and activation. Interestingly, the increases in both total and phosphorylated ERK1/2 and ERK5 following Akt-inhibition were dose-dependent, meriting further study. Excised mammary tumors from our animal model demonstrated an age-dependent increase in both ERK1/2 and ERK5. Notably, an age-dependent decrease in Akt was also observed, supporting the hypothesis that crosstalk between these pathways may exist. Future studies involving dual kinase inhibition are planned to further assess crosstalk and proliferation. The data obtained from these studies indicate the presence of crosstalk between the ERK1/2, ERK5 and Akt pathways. A better understanding of this crosstalk may lead to patient-specific drug regimens to decrease the cytotoxic effects of chemotherapeutics and improve patient mortality. 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 2242. doi:1538-7445.AM2012-2242
Differences in the prevalence of colorectal polyps in patients undergoing endoscopic removal of gastric adenoma or early gastric cancer and in healthy individuals
Authors: M. Joo, J.-J. Park, W. Lee, B. Lee, J. Hwang, S.-H. Kim, W. Jung, J. Kim, J. Yeon, J. Kim, K. Byun, Y. Bak
Journal: Endoscopy (2010)

Background and aims: We compared the prevalence of adenomatous and cancerous colon polyps in patients who underwent endoscopic removal of gastric neoplasms and in healthy controls.
Effect of disodium cromoglycate (Intal) on sputum protein composition
Authors: S. Heilpern, A. S. Rebuck
Journal: Thorax (1972)

The protein content in the sputum of nine patients with asthma was compared with that in 11 non-asthmatic patients by a method of gel electrophoresis. It was found that the albumin content was significantly higher in the sputum of the asthmatics than of the non-asthmatics (P&lt;0·01). A further 11 asthmatic patients who were taking disodium cromoglycate (Intal) as part of their treatment had sputum albumin levels indistinguishable from the non-asthmatics. When patients with asthma were then studied serially, before and after disodium cromoglycate therapy, the albumin content returned to non-asthmatic levels within two days of starting treatment. It is suggested that disodium cromoglycate has a previously unrecognized action in altering sputum proteins.
Abstract 1002: Induced dependency on amino acid metabolism in proliferating cancer cells upon PKM2 activation
Authors: Charles Kung, Shengfang Jin, Jeff Hixon, Stefan Gross, Yi Gao, Fang Cheng, Xiling Wang, Shaohui Wang, Francesco Salituro, Jeff Saunders, Ed Driggers, Kevin Marks, Hin Koon Woo, Stuart Murray, Sung Choe, Hua Yang, Katherine Yen, Michael Su, Lenny Dang
Journal: Cancer Research (2012)

Abstract It is well recognized that proliferating tumor cells invariably utilize aerobic glycolysis to support their high metabolic demands. Recent studies have further elucidated the paradoxical observation that this increase in glycolysis in proliferating tumor cells is often coupled with a molecular switch from the constitutively high activity PKM1 isoform to the modulated lower activity PKM2 isoform1,2, effectively constraining lower glycolysis at the last pyruvate kinase step. Here, we report an unanticipated link between glucose metabolism and amino-acid metabolic pathways in cancer cells. We characterized the biochemical and cellular effects of a small-molecule allosteric activator of the M2 isoform of pyruvate kinase (AGX-257) in various cancer cell types. We demonstrate that activation of PKM2 results in a metabolic rewiring of specific cancer cells that results in a profound dependency on the presence of the normally non-essential amino acid serine for continued cell proliferation. The induced serine auxotrophy by PKM2 activation is concomitant with reduced flux through the endogenous serine biosynthetic pathway and increased levels of high affinity serine transporters. PKM2 activators, possibly in combination with agents that modulate the cellular and extracellular serine pools, could form the basis for a new approach toward developing therapy for treating cancer. References: 1 Christofk, H. R. et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452, 230-233 (2008). 2 Clower, C. V. et al. The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism. Proc Natl Acad Sci U S A 107, 1894-1899 (2010). 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 1002. doi:1538-7445.AM2012-1002
ASXL1, TP53 and IKZF3 mutations are present in the chronic phase and blast crisis of chronic myeloid leukemia
Authors: J Menezes, R N Salgado, F Acquadro, G Gómez-López, M C Carralero, A Barroso, F Mercadillo, L Espinosa-Hevia, J G Talavera-Casañas, D G Pisano, S Álvarez, J C Cigudosa
Journal: Blood Cancer Journal (2013)

ASXL1 ,  TP53  and  IKZF3  mutations are present in the chronic phase and blast crisis of chronic myeloid leukemia
Acute High-Altitude Illnesses
Authors: Peter Bärtsch, Erik R. Swenson
Journal: New England Journal of Medicine (2013)

Persons who are not acclimatized to high altitudes and who ascend to 2500 m are at risk for acute high-altitude illnesses. This article reviews approaches to prevention (e.g., slow ascent, inclusion of a rest day during ascent, and medications) and treatment.
Symptomatic Hypercalcaemia in Thyrotoxicosis
Authors: R. G. Twycross, V. Marks
Journal: BMJ (1970)

In three patients with thyrotoxicosis and with symptomatic hypercalcaemia antithyroid therapy restored the plasma calcium concentration to normal, though initially in one case intravenous and oral neutral phosphate solution were required to curtail intractable vomiting.Nine cases have been recorded in which the plasma calcium concentration returned to normal after antithyroid treatment was started; all but one became normocalcaemic within eight weeks. It is suggested that in hypercalcaemic thyrotoxicosis a second pathological condition should be considered only if the plasma calcium concentration fails to return to normal within eight weeks.
Dose dependency of aflatoxin B1 binding on human high molecular weight DNA in the activation of proto-oncogene.
Authors: S S Yang, J V Taub, R Modali, W Vieira, P Yasei, G C Yang
Journal: Environmental Health Perspectives (1985)

The binding of aflatoxin B1, AFB1, a potent hepatocarcinogen, to various high molecular weight (HMW) DNAs from human normal liver and two liver cancer cell lines, Alexander primary liver carcinoma (PLC) and Mahlavu hepatocellular carcinoma (hHC) and from NIH/3T3 cell have been investigated. The kinetics of AFB1 binding to these DNAs showed similar initial rates but the extents of binding to the PLC and hHC DNAs seemed to be slightly higher. Preferential AFB1 bindings were identified in both PLC and hHC DNAs compared to normal liver DNA when analyzed by restriction endonuclease digestions and agarose gel electrophoresis. A critical AFB1 binding dosage, ranging 100 to 460 fmole/microgram DNA, was found to activate the carcinogenic effect of the Mahlavu hHC HMW DNA, but not normal liver HMW DNA, rendering it capable of inducing focal transformation in NIH/3T3 cell. Excessive AFB1 binding on the hHC and PLC HMW DNAs resulted in an
Surgery for All: A View From the Developing World
Authors: William V. Dolan
Journal: JAMA (1995)

Intestinal anthrax. Nylon fishing line as suture. Ether anesthesia for safety and cost.<i>Surgery for All: A View From the Developing World</i>is not a typical Western surgical text. The contributors draw upon their experience as surgical educators in the Islamic world of Asia, Africa, and the Middle East. The modest volume does not attempt an encyclopedic grasp of surgical theory and practice, but rather offers a fresh perspective, applying the art and science of surgery to the real-life setting of the practitioner in the developing world. This fascinating work focuses on the "sensible priorities for surgical care in most regionally prevalent diseases." Given the population and health resource constraints of the Third World,<i>Surgery for All</i>offers a significant potential impact for the indigent majority of our global village. The secret lies in the "two T's" of treatment and training. Curative surgery can provide a lifetime benefit for both
Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes as an In Vitro Model for Coxsackievirus B3–Induced Myocarditis and Antiviral Drug Screening Platform
Authors: Arun Sharma, Caleb Marceau, Ryoko Hamaguchi, Paul W. Burridge, Kuppusamy Rajarajan, Jared M. Churko, Haodi Wu, Karim I. Sallam, Elena Matsa, Anthony C. Sturzu, Yonglu Che, Antje Ebert, Sebastian Diecke, Ping Liang, Kristy Red-Horse, Jan E. Carette, Sean M. Wu, Joseph C. Wu
Journal: Circulation Research (2014)

Rationale: Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. A major causative agent for viral myocarditis is the B3 strain of coxsackievirus, a positive-sense RNA enterovirus. However, human cardiac tissues are difficult to procure in sufficient enough quantities for studying the mechanisms of cardiac-specific viral infection. Objective: This study examined whether human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. Methods and Results: hiPSC-CMs were infected with a luciferase-expressing coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs for alterations in cellular morphology and calcium handling. Viral proliferation in hiPSC-CMs was quantified using bioluminescence imaging. Antiviral compounds including interferonβ1, ribavirin, pyrrolidine dithiocarbamate, and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with reported drug effects in previous studies. Mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways after interferonβ1 treatment. Conclusions: This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to predict antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that can screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion.