tbuckley/cabot-search huggingface dataset:
Multiple Growth Factors Modulate mRNA Expression of Angiotensin II Type-2 Receptor in R3T3 Cells
Authors: Toshihiro Ichiki, Yoshikazu Kambayashi, Tadashi Inagami
Journal: Circulation Research (1995)

Abstract Previous studies showed that angiotensin II type-2 receptor (AT 2 ) sites were increased when R3T3 cells were growth arrested and decreased when they were stimulated with fibroblast growth factor or serum. We examined the effects of several other growth factors on the expression of AT 2 mRNA to clarify the relation between the AT 2 receptor and growth factors. R3T3 cells were cultured in the medium containing 10% FCS until they were confluent, and then serum was removed. AT 2 mRNA was increased after serum was depleted, and the expression level reached a plateau after 2 days of serum depletion. The presence of serum (10%), fibroblast growth factor (10 ng/mL), or lysophosphatidic acid (1 μmol/L) reduced the AT 2 mRNA expression. Phorbol ester (1 to 100 nmol/L) also suppressed the AT 2 mRNA expression in a dose-dependent manner. Interleukin-1β (1 ng/mL) enhanced the AT 2 mRNA expression 1.6-fold and the AT 2 receptor number 1.4-fold. Insulin (100 nmol/L) enhanced AT 2 mRNA expression 1.4-fold and the AT 2 receptor number 1.6-fold. These results suggest that AT 2 mRNA expression is modulated by multiple growth factors in both positive and negative directions. The presence of potential cis DNA elements that respond to interleukin-1β (CCAAT enhancer binding protein site), insulin [insulin response sequence of phospho(enol)pyruvate carboxykinase gene], and phorbol ester (AP-1 site) in the promoter region of the mouse AT 2 gene suggests that the effects of these growth factors and phorbol ester may be mediated via these cis DNA elements.
THE MECHANISM OF TOXIC ACTION OF ARSPHENAMIN ON THE HEART
Authors: WILLIAM D. REID
Journal: JAMA (1925)

When arsphenamin was introduced by Ehrlich, it was stated that the drug was contraindicated if the patient's heart was diseased. Nevertheless, arsphenamin and the allied preparations of arsenic have been widely used in the treatment of patients with known heart disease. Although favorable results have often been achieved, there have been a sufficient number of cases in which untoward effects, often fatal, on the heart have occurred, so that today clinicians of wide experience are cautious in the administration of the newer preparations of arsenic to patients with heart disease. It is not my purpose to discuss the noncardiac toxic reactions of arsphenamin; I am concerned here with those instances in which there is a development of, or an increase in, the degree of heart failure, and especially with the sudden deaths after the injection of the drug, such as that reported by Stokes.<sup>1</sup> The principal explanations given for
Abstract B35: Target discovery: Using VBIM technique to identify carboplatin resistance genes in ovarian cancer cells
Authors: Han Wei, Tao Lu
Journal: Clinical Cancer Research (2013)

Abstract Among gynecological cancers, ovarian cancer is the leading cause of death each year. Women are often diagnosed with an advanced stage of the disease as it is frequently without overt or specific symptoms until late in its development. One of the major chemotherapy drugs used to treat ovarian cancer is carboplatin. Carboplatin was introduced in the late 1980s and has since gained popularity in clinical treatment due to its vastly reduced side-effects compared to its parent compound, cisplatin. Although resistance to carboplatin remains a major barrier to the successful treatment of ovarian cancer, the mechanisms of its resistance are poorly understood. In this study, we used the novel validation-based insertional mutagenesis (VBIM) technique to identify carboplatin resistance genes in ovarian cancer cells and to further confirm and evaluate their role in mediating carboplatin resistance in ovarian cancer cells. In a preliminary screen, we identified three novel proteins whose functions have never been previously linked to carboplatin resistance in ovarian cancer. We name them ovarian cancer carboplatin resistance genes OCCRP-1, 2 and 3. By generating stable A2780 cells in which OCCRP-1 is either overexpressed or knocked down, we confirmed that OCCRP-1 is a carboplatin resistance gene in ovarian cancer cells. Similar work is carrying on for OCCRP-2 and 3 as well. Our study promises to discover novel mechanisms of gene-mediated carboplatin resistance so that reversal or bypass of this resistance in ovarian cancer can be achieved by developing small chemical inhibitors which ultimately will lead to novel therapeutic approaches for ovarian cancer treatment. Citation Format: Han Wei, Tao Lu. Target discovery: Using VBIM technique to identify carboplatin resistance genes in ovarian cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr B35.
The Use of Seat Belts
Authors: Steven A. Rosenfeld
Journal: JAMA (1987)

<h3>To the Editor.—</h3> The fact that anyone would make an effort to trivialize the issue of seat belts and safety is incomprehensible to me. Surprisingly, this is what Weissman<sup>1</sup>did in his letter to the editor in the March 20 issue ofThe Journal. I interpret his conclusion to be that the time spent buckling a seat belt is wasted because of the meager return expected. Has Dr Weissman spent time recently in a pediatric or surgical intensive care unit? I ask this question because I recently spent some time in the pediatric intensive care unit of the University of Massachusetts Medical Center. The patient I observed while I was adjusting his intracranial pressure monitoring system is a 5-year-old boy who was an automobile passenger not protected by a seat belt. After a collision with another vehicle, the automobile in which he was riding overturned and he was thrown
Is digoxin a designer oestrogen?
Authors: Debra H Schussheim, Adam E Schussheim
Journal: The Lancet (1998)

Selective oestrogen receptor modulators (SERMs) are the new designer oestrogens, constructed to exert tissue-specific oestrogen effects. With the US Food and Drug Administration approval in December, 1997, of the first SERM, raloxifene, a new age of preventive health for women is upon us. But perhaps these drugs are not as new as they are purported to be. There is some evidence that digoxin may share intriguing similarities to SERMs. Cardiac glycosides share a structural homology with steroid hormones (figure) which has prompted investigations of possible functional similarities. In 1979, The Lancet published an epidemiological review by the US National Cancer Institute which showed that women with breast cancer who took digoxin had smaller, less aggressive tumours and were less likely to develop metastatic disease than those not on digoxin.1Stenkvist B Bengtsson E Eriksson O et al.Cardiac glycosides and breast cancer.Lancet. 1979; i: 563Abstract Scopus (123) Google Scholar The investigators concluded that digoxin “interferes with the oestrogen receptors in some way”. This finding is supported by the well-recognised oestrogen-like side-effect of digoxin—gynecomastia in men. The effects of cardiac glycosides on the rat uterus has been reported. Digitoxin, like oestradiol, significantly increased uterine weight in rats, whereas digoxin did not.2Rifka SM Pita JC Loriaux DL Mechanisms of interactions of digitalis with estradiol binding sites in rat uteri.Endocrinology. 1976; 99: 1091-1096Crossref PubMed Scopus (42) Google Scholar Conversely, more recent studies suggest that oestrogens may modulate the autonomic nervous system;3Huikuri HV Pikkujamsa SM Airaksinen KE et al.Sex-related differences in autonomic modulation of heart rate in middle-aged subjects.Circulation. 1996; 94: 122-125Crossref PubMed Scopus (362) Google Scholar an effect touted as one of digoxin's possible mechanisms of action. In fact, digoxin's potential salubrious actions have been poorly defined—maybe they are oestrogenic in nature? We are unaware of any published reports of the effect of cardiac glycosides on lipid profiles and perhaps future studies will address digoxin's effects on bone metabolism. As with most advances in medicine, new therapeutics prompt examination of older agents. Our old friend digoxin may be more in vogue than we thought. Could this agent have tissue-specific oestrogen effects, like the new designer oestrogens?
Annoyance due to low frequency hums
Authors: C G Rice
Journal: BMJ (1994)

prophylaxis at caesarean section28 the report could have been more forthright.The latest report makes it abundantly clear, however, that little will change unless such recommendations are put into practice.The report now also contains a chapter on maternal mortality in Europe.Although major differences in reporting and classifying maternal deaths remain, such an endeavour may contribute to a greater degree of uniformity in data collection and analysis, if not throughout Europe, at least within the European Union.After all, some of the smaller countries have only a handful of maternal deaths each year.Even in the large countries of Europe, important contributors rarely occur often enough for inferences to be drawn promptly.Would it not be a great leap forward if adding a European chapter to the successful combination of the countries of the United Kingdom were to lay the foundation for confidential inquiries at a European level?On the basis of what can be learnt from the latest British report this is bound to be of great benefit to all who manage, provide, and use maternity services.
1050 EXCLUSION OF THE PERCUTANEOUS LIVER BIOPSY FROM THE MANAGEMENT OF CHRONIC HEPATITIS B AND C PATIENTS: ARE ESSENTIAL SECONDARY DIAGNOSES BEING MISSED?
Authors: H. Chi, C. Verveer, B.E. Hansen, P.E. Zondervan, H.L.A. Janssen, R.J. de Knegt
Journal: Journal of Hepatology (2012)
Mannitol infusions and lithium excretion.
Authors: A Obek
Journal: BMJ (1972)

thyroxine 0.1 uig/100 ml, total fats 1,820 mg/100 ml, cholesterol 523 mg/100 ml, urea 516 mg/100 ml, creatinine 6.6 mg/100 ml, and uric acid 17 mg/100 ml.The glomerular filtration rate measured by creatinine clearance was 7 ml/min.The bladder was drained by an indwelling catheter and the patient was given triiodothyronine.After 10 days she recovered bladder control, the urea was 80 mg/ 100 ml, and the creatinine clearance 25 ml/min.The electroencephalogram became normal.After four months the urea was 42 mg/ 100 ml and the creatinine clearance 82 ml/min, and the patient was well in herself.Though myxoedema has been shown clinically and experimentally to cause weak- ness of the bladder muscle' we have not found any reports in the literature of renal failure occurring, as in our case.Retention of urine must now be included among the various clinical forms in which myxoedema presents itself.-Weare, etc.,
Phase 2 study of alemtuzumab (anti-CD52 monoclonal antibody) in patients with advanced mycosis fungoides/Sézary syndrome
Authors: Jeanette Lundin, Hans Hagberg, Roland Repp, Eva Cavallin-Ståhl, Susanne Fredén, Gunnar Juliusson, Eija Rosenblad, Geir Tjønnfjord, Tom Wiklund, Anders Österborg
Journal: Blood (2003)
Combining Functional and Tubular Damage Biomarkers Improves Diagnostic Precision for Acute Kidney Injury After Cardiac Surgery
Authors: Rajit K. Basu, Hector R. Wong, Catherine D. Krawczeski, Derek S. Wheeler, Peter B. Manning, Lakhmir S. Chawla, Prasad Devarajan, Stuart L. Goldstein
Journal: Journal of the American College of Cardiology (2014)
Risk of Malignant Neoplasm of the Pancreas in Relation to Diabetes
Authors: Hua-Fen Chen, Peter Chen, Chung-Yi Li
Journal: Diabetes Care (2011)

We prospectively assessed the age- and sex-specific incidence and relative risk of malignant neoplasm of the pancreas in Taiwan's diabetic population.A total of 615,532 diabetic patients and 614,871 age- and sex-matched control subjects were linked to inpatient claims (2000-2006) to identify the admissions for malignant neoplasm of the pancreas (ICD-9: 157). The Cox proportional hazards regression model was used to estimate the age- and sex-specific relative risk of pancreatic neoplasm.Compared with the control group, the diabetic patients had a significantly increased risk of pancreatic cancer (hazard ratio [HR] 1.54 [95% CI 1.39-1.71]). The higher and significant age-specific HRs were observed in diabetic men (1.91) and women (1.80) aged 45-65 years.Middle-aged diabetic men and women were associated with the most increased risk of malignant neoplasm of the pancreas.
Subarachnoid Distribution of Drugs after Lumbar Injection
Authors: Richard E. Rieselbach, Giovanni Di Chiro, Emil J. Freireich, David P. Rall
Journal: New England Journal of Medicine (1962)

DIRECT injection of drugs into the subarachnoid space is required for treatment of several diseases involving the leptomeninges. This is necessary because of the virtual exclusion of certain plasma constituents by the bloodcerebrospinal-fluid barrier due to molecular size, protein binding, lipid insolubility or ionization.2 Drugs included in this category are polymyxin B and amphotericin B.3 , 4 The antimetabolites 6-mercaptopurine and methotrexate, used in the therapy of acute leukemia, do not attain significant levels in spinal fluid when administered systemically.2 , 5 Therefore, meningeal leukemia, the diffuse involvement of the meninges by leukemic cells, must often be treated with an intrathecally administered drug such . . .
Impaired localisation and transport function of canalicular Bsep in taurolithocholate induced cholestasis in the rat
Authors: F A Crocenzi
Journal: Gut (2003)

<b>Background:</b> Taurolithocholate induced cholestasis is a well established model of drug induced cholestasis with potential clinical relevance. This compound impairs bile salt secretion by an as yet unclear mechanism. <b>Aims:</b> To evaluate which step/s of the hepatocellular bile salt transport are impaired by taurolithocholate, focusing on changes in localisation of the canalicular bile salt transporter, Bsep, as a potential pathomechanism. <b>Methods:</b> The steps in bile salt hepatic transport were evaluated in rats in vivo by performing pharmacokinetic analysis of <sup>14</sup>C taurocholate plasma disappearance. Bsep transport activity was determined by assessing secretion of <sup>14</sup>C taurocholate and cholyl-lysylfluorescein in vivo and in isolated rat hepatocyte couplets (IRHC), respectively. Localisation of Bsep and F-actin were assessed both in vivo and in IRHC by specific fluorescent staining. <b>Results:</b> In vivo pharmacokinetic studies revealed that taurolithocholate (3 μmol/100 g body weight) diminished by 58% canalicular excretion and increased by 96% plasma reflux of <sup>14</sup>C taurocholate. Analysis of confocal images showed that taurolithocholate induced internalisation of Bsep into a cytosolic vesicular compartment, without affecting F-actin cytoskeletal organisation. These effects were reproduced in IRHC exposed to taurolithocholate (2.5 μM). Preadministration of dibutyryl-cAMP, which counteracts taurolithocholate induced impairment in bile salt secretory function in IRHC, restored Bsep localisation in this model. Furthermore, when preadministered in vivo, dibutyryl-cAMP accelerated recovery of both bile flow and bile salt output, and improved by 106% the cumulative output of <sup>14</sup>C taurocholate. <b>Conclusions:</b> Taurolithocholate impairs bile salt secretion at the canalicular level. Bsep internalisation may be a causal factor which can be prevented by dibutyryl-cAMP.
Capsule Endoscopy Structured Terminology (CEST): Proposal of a Standardized and Structured Terminology for Reporting Capsule Endoscopy Procedures
Authors: L. Y. Korman, M. Delvaux, G. Gay, F. Hagenmuller, M. Keuchel, S. Friedman, M. Weinstein, M. Shetzline, D. Cave, R. de Franchis
Journal: Endoscopy (2005)

This Capsule Endoscopy Structured Terminology (CEST) is a copyrighted work, protected by United States and worldwide copyright laws and treaties. Users of the CEST are hereby granted a free license to use, copy or distribute the CEST in connection with supporting a structured terminology for capsule endoscopy, subject to the following conditions:
Relationships between insulin resistance and lipoproteins in nondiabetic African Americans, Hispanics, and non-Hispanic whites: The insulin resistance atherosclerosis study
Authors: Barbara V. Howard, Elizabeth J. Mayer-Davis, David Goff, Daniel J. Zaccaro, Ami Laws, David C. Robbins, Mohammad F. Saad, Joseph Selby, Richard F. Hamman, Ronald M. Krauss, Steven M. Haffner
Journal: Metabolism (1998)
INGUINAL HERNIA FOLLOWING APPENDECTOMY
Authors: ALANSON M. POND
Journal: JAMA (1910)

During the past twenty-five years the pathology of appendicitis has been cleared up and the operative treatment has been elaborated and commented on so extensively that the entire country has been thoroughly informed of the gravity of the condition and equally convinced of the necessity for surgical treatment. Dexterous surgeons perform appendectomy with such marvelous simplicity and rapidity before admiring classes and visitors that the latter are impressed with the ease and rapidity of the operation, and fail utterly to realize that there is a surgical reason for every step of this procedure, or that this seasoned operator has worked many months or years to perfect his technic and to study out his attack along the lines of proper surgical anatomy. They see only the simplified application of correct principles.  The result of this is that surgery of the vermiform appendix is more extensively practiced than ever before, and consequently
How the language capacity was naturally selected: Altriciality and long immaturity
Authors: D. Kimbrough Oller, Ulrike Griebel
Journal: Behavioral and Brain Sciences (2006)

Critical factors that appear to encourage vocal development in humans are altriciality and long immaturity. Hominid infants appear to have evolved a specific tendency to use elaborate vocalization as a means of soliciting long-term investment from caregivers. The development of such vocal capacity provides necessary infrastructure for language development across human life history.
Leprosy in Norway.
Authors: W. S. Caldwell
Journal: JAMA (1897)

Vienna, Austria, Nov, 12, 1897. <h3>To the Editor:</h3> —I was much surprised while visiting Norway during the last summer, to find that among a population of less than two million people, there existed three special hospitals for the confinement and treatment of lepers, and that in these institutions were domiciled over one thousand unfortunates, afflicted with this terrible disease. By far the largest of these institutions is situated at Bergen, and while there I availed myself of the opportunity to visit it. The superintendent, Dr. Hansen, was away on a vacation, but his first assistant received me cordially, and answered all my queries in the politest manner possible. Naturally, where a fish diet forms so large a part of the food of the population of this country, one asks the question whether this may not act as a strong causative factor in the production of the disease. I was told
Reductive dechlorination of tetrachloroethene by a high rate anaerobic microbial consortium.
Authors: S H Zinder, J M Gossett
Journal: Environmental Health Perspectives (1995)

Tetrachloroethene (PCE) and other chloroethenes are major contaminants in groundwater, and PCE is particularly resistant to attack by aerobes. We have developed an anaerobic enrichment culture that carries out reductive dechlorination of chloroethenes to ethene at high rates, thereby detoxifying them. Although the electron donor added to the culture is methanol, our evidence indicates that H2 is the electron donor used directly for dechlorination. We have recently obtained a culture from 10(-6) dilution of the original methanol/PCE culture that uses H2 as an electron donor for PCE dechlorination. Because the culture can be transferred indefinitely and the rate of PCE dechlorination increases after inoculation, we suggest that dechlorinating organisms in the culture use the carbon-chlorine bonds in chloroethenes as electron acceptors for energy conservation.
Essays
Authors: William A. Sodeman
Journal: JAMA (1999)

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Response to Letter Regarding Article, “Hydralazine and Isosorbide Dinitrate in Heart Failure: Historical Perspectives, Mechanisms, and Future Directions”
Authors: Robert T. Cole, Andreas P. Kalogeropoulos, Vasiliki V. Georgiopoulou, Arshed A. Quyyumi, Javed Butler, Mihai Gheorghiade, Clyde Yancy
Journal: Circulation (2011)

We appreciate the careful review by Drs Taylor, Hare, and Mann of our article 1 and their thoughtful letter in response to it.The importance of studying the combination of hydralazine and isosorbide dinitrate in heart failure has been highlighted both by our review and by their letter.It is not uncommon for drug research and development to fall into either of the 2 following scenarios.Some drugs may enter phase III trials without a comprehensive understanding of their systemic and organ-specific mechanistic effects.In addition, their potential for differential impact on specific clinical and demographic subgroups is largely unrecognized.Alternatively, novel agents may never enter definitive trials because the multitude of questions that need to be answered in phase I and II studies may be deemed too unattractive financially, leading to the shelving of novel agents.The scientific community finds itself in an unusually good position with hydralazine and isosorbide dinitrate use in heart failure because of the wealth of clinical and translational research data that have accumulated over the years in this respect.Many data elements needed for effective clinical trial design with respect to specific aims or target groups of interest are already available.These include biological mechanisms of action, race, and sex-related signals, data on genetic heterogeneity, and specific clinical scenarios, eg, chronic versus acute heart failure.Moreover, existing data are largely encouraging, suggesting that further investment in studying this combination will likely be of societal benefit, will be less risky, and will help to further our aim of moving toward personalized medicine.We agree also with the authors that it is worth studying other agents that modulate nitric oxide pathobiology.Besides its direct effects on the myocardium, nitric oxide bioavailability also modulates systemic vascular and endothelial function, 2 ischemia, 3 arrhythmias, 4 renal function, 5 and pulmonary vascular function. 6These are all major determinants of heart failure progression and outcomes, underscoring the need to further investigate this pathway in patients with heart failure.We thank the authors for their interest in our article.