tbuckley/cabot-search huggingface dataset:
Mortality From Diabetes in Nauru: Results of 4-Yr Follow-Up
Authors: Paul Z Zimmet, Caroline F Finch, Michael G Schooneveldt, Hilary O King, Kiki Thoma
Journal: Diabetes Care (1988)

A population survey in 1982 confirmed that Nauruan adults suffer from an extremely high prevalence (24%) of non-insulin-dependent diabetes mellitus. A follow-up study of the survey subjects was conducted in 1986. The aim was to assess the burden of diabetes to Nauruans in terms of premature mortality. Age-adjusted mortality rates for diabetic subjects were significantly increased when compared with normal subjects (relative risks for 4-yr mortality were 4.53 in men, P &amp;lt; .01, and 3.96 in women, P &amp;lt; .05). Although there was an excess number of deaths among diabetic subjects compared with normal subjects and subjects with impaired glucose tolerance, there was no significant association between cause of death and diabetes.
A Novel Two-Step Hierarchical Quantitative Structure–Activity Relationship Modeling Work Flow for Predicting Acute Toxicity of Chemicals in Rodents
Authors: Hao Zhu, Lin Ye, Ann Richard, Alexander Golbraikh, Fred A. Wright, Ivan Rusyn, Alexander Tropsha
Journal: Environmental Health Perspectives (2009)

Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening.A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects.A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC(50)) and in vivo rodent median lethal dose (LD(50)) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure-activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD(50) values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC(50) and LD(50). However, a linear IC(50) versus LD(50) correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC(50) and LD(50) values: One group comprises compounds with linear IC(50) versus LD(50) relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD(50) values from chemical descriptors. All models were extensively validated using special protocols.The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity.
JNK: A double-edged sword in tumorigenesis
Authors: Francisco Javier Cubero, Gang Zhao, Christian Trautwein, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2011)

The c-Jun NH2-terminal kinase (JNK) signal-transduction pathway has been implicated in the growth of carcinogen-induced hepatocellular carcinoma. However, the mechanism that accounts for JNK-regulated tumor growth is unclear. Here, we demonstrate that compound deficiency of the two ubiquitously expressed JNK isoforms (JNK1 and JNK2) in hepatocytes does not prevent hepatocellular carcinoma development. Indeed, JNK deficiency in hepatocytes increased the tumor burden. In contrast, compound JNK deficiency in hepatocytes and nonparenchymal cells reduced both hepatic inflammation and tumorigenesis. These data indicate that JNK plays a dual role in the development of hepatocellular carcinoma. JNK promotes an inflammatory hepatic environment that supports tumor development, but also functions in hepatocytes to reduce tumor development.
Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial
Authors: François Raffi, Hans Jaeger, Eugenia Quiros-Roldan, Helmut Albrecht, Elena Belonosova, Jose M Gatell, Jean-Guy Baril, Pere Domingo, Clare Brennan, Steve Almond, Sherene Min
Journal: The Lancet Infectious Diseases (2013)
ERGOT IN PURPURA
Authors: John G. Downing
Journal: JAMA (1934)

<h3>To the Editor:—</h3> In a communication under the title "Use of Ergot to Contract Capillaries in Purpura" (The Journal, Dec. 30, 1933, p. 2137) J. C. Norris mentioned the use of this solution in drachm doses, and solution of pituitary, 0.5 cc., hypodermically. The use of ergot in purpura is an old time remedy. In the<i>Journal of Cutaneous and Genito-Urinary Diseases</i>(<b>9</b>:241 [July] 1891) W. L. Munroe tells of a peculiar exanthem following an attack of epidermic influenza. The eruption consisted of a hemorrhagic exanthem. Part of the treatment given was as follows: Tr. ferri chloridi..... Ext. ergotae fl..... āā m xx t. i. d. Ergot was not an uncommon ingredient in prescriptions used in purpuric conditions of the skin at that time, but it fell into disrepute on account of the danger of producing ergotism.
Compartment-Specific Isoforms of TPI and GAPDH are Imported into Diatom Mitochondria as a Fusion Protein: Evidence in Favor of a Mitochondrial Origin of the Eukaryotic Glycolytic Pathway
Authors: Marie-Françoise Liaud, Christiane Lichtl, Kirk Apt, William Martin, Rüdiger Cerff
Journal: Molecular Biology and Evolution (2000)

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and triosephosphate isomerase (TPI) are essential to glycolysis, the major route of carbohydrate breakdown in eukaryotes. In animals and other heterotrophic eukaryotes, both enzymes are localized in the cytosol; in photosynthetic eukaryotes, GAPDH and TPI exist as isoenzymes that function in the glycolytic pathway of the cytosol and in the Calvin cycle of chloroplasts. Here, we show that diatoms—photosynthetic protists that acquired their plastids through secondary symbiotic engulfment of a eukaryotic rhodophyte—possess an additional isoenzyme each of both GAPDH and TPI. Surprisingly, these new forms are expressed as an TPI-GAPDH fusion protein which is imported into mitochondria prior to its assembly into a tetrameric bifunctional enzyme complex. Homologs of this translational fusion are shown to be conserved and expressed also in nonphotosynthetic, heterokont-flagellated oomycetes. Phylogenetic analyses show that mitochondrial GAPDH and its N-terminal TPI fusion branch deeply within their respective eukaryotic protein phylogenies, suggesting that diatom mitochondria may have retained an ancestral state of glycolytic compartmentation that existed at the onset of mitochondrial symbiosis. These findings strongly support the view that nuclear genes for enzymes of glycolysis in eukaryotes were acquired from mitochondrial genomes and provide new insights into the evolutionary history (host-symbiont relationships) of diatoms and other heterokont-flagellated protists.
Possible role of adenosine in the macula densa mechanism of renin release in rabbits.
Authors: S Itoh, O A Carretero, R D Murray
Journal: Journal of Clinical Investigation (1985)

This study was designed to examine: (a) the effects of adenosine and its analogues on renin release in the absence of tubules, glomeruli, and macula densa, and (b) whether adenosine may be involved in a macula densa-mediated renin release mechanism. Rabbit afferent arterioles (Af) alone and afferent arterioles with macula densa attached (Af + MD) were microdissected and incubated for two consecutive 30-min periods. Hourly renin release rate from a single arteriole (or an arteriole with macula densa) was calculated and expressed as ng AI X h-1 X Af-1 (or Af + MD-1)/h (where AI is angiotensin I). Basal renin release rate from Af was 0.69 +/- 0.09 ng AI X h-1 X Af-1/h (means +/- SEM, n = 16) and remained stable for 60 min. Basal renin release rate from Af + MD was 0.20 +/- 0.04 ng AI X h-1 X Af + MD-1/h (n = 6), which was significantly lower (P less than 0.0025) than that from Af. When adenosine (0.1 microM) was added to Af, renin release decreased from 0.72 +/- 0.16 to 0.24 +/- 0.04 ng AI X h-1 X Af-1/h (P less than 0.025; n = 9). However, when adenosine was added to Af + MD, no significant change in renin release was observed. N6-cyclohexyl adenosine (an A1 adenosine receptor agonist) at 0.1 microM decreased renin release from Af from 0.69 +/- 0.14 to 0.39 +/- 0.12 ng AI X h-1 X Af-1/h (n = 5, P less than 0.05). However, 5'-N-ethylcarboxamide adenosine (an A2 adenosine receptor agonist) either at 0.1 microM or at 10 microM had no effect. Theophylline, at a concentration (10 microM) that does not block phosphodiesterase but does block adenosine receptors, increased renin release from Af + MD from 0.21 +/- 0.03 to 0.46 +/- 0.08 ng AI X h-1 X Af + MD-1/h (P less than 0.05; n = 8). The results are consistent with the hypotheses that adenosine decreases renin release via the activation of A1 adenosine receptors, and that adenosine may be an inhibitory signal from the macula densa to juxtaglomerular cells.
The transcription factor DREAM represses the deubiquitinase A20 and mediates inflammation
Authors: Chinnaswamy Tiruppathi, Dheeraj Soni, Dong-Mei Wang, Jiaping Xue, Vandana Singh, Prabhakar B Thippegowda, Bopaiah P Cheppudira, Rakesh K Mishra, Auditi DebRoy, Zhijian Qian, Kurt Bachmaier, You-Yang Zhao, John W Christman, Stephen M Vogel, Averil Ma, Asrar B Malik
Journal: Nature Immunology (2014)
Lessons from Scotland's experience of alcohol pricing
Authors: P. Rice
Journal: BMJ (2014)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Lessons from Scotland’s experience of alcohol pricing Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Narrower Margins for Clinical Stage I Malignant Melanoma
Authors: Calvin L. Day, Martin C. Mihm, Arthur J. Sober, Thomas B. Fitzpatrick, Ronald A. Malt
Journal: New England Journal of Medicine (1982)

Panic after a diagnosis of cutaneous malignant melanoma commonly arises from fears of early death and disfiguring surgery. Yet, in the United States today, most cutaneous melanomas are diagnosed while they are in an early and curable stage, before metastases have occurred. We submit that surgery more conservative than that commonly practiced is warranted not only for these localized melanomas but also for some melanomas with a greater probability of metastasizing. This conclusion is based on our experience and on recent reports showing that the magnitude of surgical resection margins has no effect on survival, even for high-risk melanomas.1 2 3 Early . . .
Rationality versus program-based behavior
Authors: Geoffrey M. Hodgson
Journal: Behavioral and Brain Sciences (2007)

For Herbert Gintis, the “rational actor,” or “beliefs, preferences, and constraints (BPC),” model is central to his unifying framework for the behavioral sciences. It is not argued here that this model is refuted by evidence. Instead, this model relies ubiquitously on auxiliary assumptions, and is evacuated of much meaning when applied to both human and nonhuman organisms. An alternative perspective of “program-based behavior” is more consistent with evolutionary principles.
Low Circulating Folate and Vitamin B <sub>6</sub> Concentrations
Authors: Killian Robinson, Kristopher Arheart, Helga Refsum, Lars Brattström, Godfried Boers, Per Ueland, Paolo Rubba, Roberto Palma-Reis, Raymond Meleady, Leslie Daly, Jacqueline Witteman, Ian Graham
Journal: Circulation (1998)

Background —A high plasma homocysteine concentration is a risk factor for atherosclerosis, and circulating concentrations of homocysteine are related to levels of folate and vitamin B 6 . This study was performed to explore the interrelationships between homocysteine, B vitamins, and vascular diseases and to evaluate the role of these vitamins as risk factors for atherosclerosis. Methods —In a multicenter case-control study in Europe, 750 patients with documented vascular disease and 800 control subjects frequency-matched for age and sex were compared. Plasma levels of total homocysteine (before and after methionine loading) were determined, as were those of red cell folate, vitamin B 12 , and vitamin B 6 . Results —In a conditional logistic regression model, homocysteine concentrations greater than the 80th percentile for control subjects either fasting (12.1 μmol/L) or after a methionine load (38.0 μmol/L) were associated with an elevated risk of vascular disease independent of all traditional risk factors. In addition, concentrations of red cell folate below the lowest 10th percentile (&lt;513 nmol/L) and concentrations of vitamin B 6 below the lowest 20th percentile (&lt;23.3 nmol/L) for control subjects were also associated with increased risk. This risk was independent of conventional risk factors and for folate was explained in part by increased homocysteine levels. In contrast, the relationship between vitamin B 6 and atherosclerosis was independent of homocysteine levels both before and after methionine loading. Conclusions —Lower levels of folate and vitamin B 6 confer an increased risk of atherosclerosis. Clinical trials are now required to evaluate the effect of treatment with these vitamins in the primary and secondary prevention of vascular diseases.
Abstract 418: Introducing different genetic elements into human mesenchymal stem cells to transform into osteosarcoma
Authors: Lukas Austin-Page, Sajida Thein, Matthrew Lam, Amy Park, Nan Li, Rui Yang, Richard Gorlick
Journal: Cancer Research (2010)

Abstract Despite Osteosarcoma (OS) being the most common primary malignant bone tumor in children and young adults, little clarity exists in where the cell of origin exists in the pathway of differentiation between a human mesenchymal stem cell (hMSC) and a mature osteoblast. It is similarly unclear the primary genetic alterations which initiate oteosarcoma formation in patients. Since high grade OS usually demonstrates histologic variability, and the potential for multilineage differentiation, along with some direct experimental observations some consider hMSC as the cell of origin of OS whereas others believe the pre-osteoblast or osteoblast to be the mot likely cell of origin. Our previous studies have shown that serially introducing 3 different viral constructs, hTERT, SV40TAg, and H-RAS, transforms hMSC into 2 distinct sarcomas cell lines, but not OS. This may be attributable to the fact that oncogenic H-Ras does not seem to play a direct role in the pathogenesis of OS. Therefore, the MSC-TS cell line, hMSC transfected with hTERT and SV40TAg can be used as a platform for further analysis of the impact of genetic transformation of hMSCs. The MSC-TS cells were transformed with lentivirus containing human β-catenin (β), and IGF-1R (I) , separately. Both β-catenin and IGF-1R have been suggested to be involved in the pathogenesis of OS due to their proliferative and/or anti-apoptotic effects. Drug resistant colonies were picked up 21 days after selection to obtain stably transfected cell lines, MSC-TS-β, and MSC-TS-I, respectively. Western blots were carried out to detect the protein of β-catenin and IGF-1R, respectively. Clones, which have highest, lowest, and intermediate protein levels were selected, and comparison between the lines and characterizations are completed and underway. Further characterization includes: 1) Soft Agar Assays , 2)Subcutaneous/Orthotopic Tumorigenicity Assays,3) Routine histological examination and also staining with immunohistochemical markers, 4) Microarray Analysis, 5) Spectral Karyotyping / Comparative Genomic Hybridization, 6) Motility and Migration Assays, and 7) Differentiation Assays. 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 418.
The Scientific Basis of Psychiatry
Authors: James J. Brophy
Journal: JAMA (1984)

The editor of this marvelous contribution notes in the introductory chapter that "the developing organism is in a dialogue with its environment." The reader can only develop a broader and more eclectic view of psychiatry in the enriching learning environment of this book. It is a balanced, terse, and relevant compendium by an imposing array of authors who have supported their material (in most cases) with an up-to-date bibliography. Dealing with populations "from the mouse to the grouse" to those who live in a house (no "cat in the hat" here), the exploration ranges from the synapse to the effect of social classes. The author of the section of neurophysiology reflects that "if the brain were simple enough for us to understand, we would be so simple that we couldn't." The authors simplify a diverse group of topics including psycholinguistics, EEGs, rating scales, genetics, and sleep. Aside from the overly
Focal Hepatic Activity During Ventilation-Perfusion Scintigraphy Due to Systemic-Portal Shunt Due to Superior Vena Cava Obstruction From Histoplasmosis-Induced Fibrosing Mediastinitis
Authors: Gavin C. Mackie, Aju Thomas, Bennett Greenspan, Amolak Singh
Journal: Clinical Nuclear Medicine (2007)

A 59-year-old woman with a history of fibrosing mediastinitis secondary to histoplasmosis diagnosed on mediastinoscopy presented with dyspnea. A ventilation-perfusion scan demonstrated decreased perfusion to the entire right lung. In addition, the perfusion images demonstrated focal abnormal activity in part of the liver. On computed tomography of the chest, there was significant soft tissue opacification in the mediastinum occluding the right pulmonary artery, with passage of the injected contrast via collateral vessels to the liver. The main collateral pathway was via the right internal thoracic vein and the umbilical vein. Pulmonary angiography confirmed complete occlusion of the right pulmonary artery.
Chronic Ammonium Hydroxide Exposure
Authors: MARIN H. KOLLEF
Journal: Annals of Internal Medicine (1987)

Letters and Corrections1 July 1987Chronic Ammonium Hydroxide ExposureMARIN H. KOLLEF, M.D.MARIN H. KOLLEF, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-107-1-118_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Ammonium hydroxide is a colorless, highly soluble, extremely irritant alkaline gas that is widely used in private and industrial settings (1). The major toxicity occurs secondary to acute exposure with severe laryngeal and pulmonary edema (2). The effects of chronic low level exposure are unknown. I recently evaluated a patient with chronic exposure who presented with possible ocular, upper airway, and pulmonary manifestations.A 54-year-old man had a history of mild hypertension and adult onset diabetes mellitus, as well as a 20 pack-year history of smoking. He had no cardiopulmonary symptoms. He was referred for evaluation of...References1. PARKES W. Occupational Lung Disorder. London: Butterworth & Company Publishers, Ltd; 1982:473. Google Scholar2. WALTON M. Industrial ammonia gassing. Br J Ind Med. 1973;30:78-86. MedlineGoogle Scholar3. SOBONYA R. Fatal anhydrous ammonia inhalation. Hum Pathol. 1977;8:293-9. CrossrefMedlineGoogle Scholar4. SPENCER H. Pathology of the Lung. Oxford: Pergamon Press Ltd; 1985:137-8. Google Scholar5. COONJONESJENKINSSIEGEL RRLJ. Animal inhalation studies on ammonia, ethylene glycol, formaldehyde, dimethylamine, and ethanol. Toxicol Appl Pharmacol 1970;16:646-55. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Madigan Army Medical Center Tacoma, WA 98433-5088 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByHazardous substances in frequently used professional cleaning products 1 July 1987Volume 107, Issue 1Page: 118-118KeywordsDiabetes mellitusEdemaHypertensionToxicity Issue Published: 1 July 1987 PDF DownloadLoading ...
Posterior Bulge Sign for Parathyroid Adenoma on Tc-99m MIBI SPECT
Authors: Mehran Bajoghli, Ashok Muthukrishnan, James M. Mountz
Journal: Clinical Nuclear Medicine (2006)

Early and 3-hour delayed Tc-99m MIBI SPECT scans were performed on a 57-year-old male patient with a high clinical suspicion of hyperparathyroidism. The early images demonstrated projection of tracer activity posterior to the inferior pole of the right thyroid lobe. The 3-hour delayed images revealed complete tracer washout from this region as well as the rest of the thyroid gland. Imaging with ultrasound, followed by surgical excision and pathology, confirmed a parathyroid adenoma. The authors present this case of posterior bulge appearance on the early Tc-99m MIBI presenting with normal clearance on the delayed images.
Quantitative defect of glycoprotein ib in severe cirrhotic patients
Authors: María J. Sánchez‐Roig, José Rivera, José M. Moraleda, Vicente Vicente García
Journal: American Journal of Hematology (1994)

Abstract A decrease of platelet agglutination induced by ristocetin has been described in Cirrhotic patients. In order to investigate the relationship of such phenomenon with a putative defect on piatelet membrane glycoprotein Ib, we have studied the quantitative and functional status of Gp Ib in eleven severe alcoholic cirrhotic patients, and the ability of their formalin‐fixed platelets to agglutinate in the presence of normal plasma plus ristocetin. Interestingly, we found a significant decrease of immunoreactive GP Ib molecules (9,978 ± 1,534 vs. 17,064 ± 404 molecules per platelet) and ristocetin‐dependent binding of vWF (9,113 ± 1,338 vs. 13,992 ± 1,968 molecules per platelet) ( P &lt; 0.01) in comparison to the levels found in a control group of healthy subjects. Immunoblotting analysis of platelet lysates confirmed the reduction of GP Ib level in cirrhotic patients, but showed no modification on the precipitation pattern of this glycoprotein. The ristocetin‐induced platelet agglutination (light transmission %) was also significantly lower in patients with Cirrhosis (48 ± 7.6 vs. 92 ± 3.6, P &lt; 0.01), and correlated with the binding of normal vWF (r = 0.863, P = 0.0013). Patients with bleeding times longer than 7 min and/or clinical history of bleeding episodes showed the lowest values of platelet agglutination and GP Ib level. In conclusion, our present results indicate that llver cirrhosis is associated with a relevant decrease of functional GP Ib molecules on the platelet surface. This reduction might be related to the prolongation of bleeding time and to the bleeding diathesis observed in cirrhotic patients. © 1994 Wiley‐Liss, Inc.
991-68 Potential Impact of Serial Drug Testing on the Clinical Outcome of Survivors of Cardiac Arrest, as Assessed in the Propafenone Arm of CASH Trial
Authors: Jürgen Siebels, Riccardo Cappato, Rudolf Rüppel, Michael Schneider, Michael Schlüter, Thomas Meinertz, Karl-Heinz Kuck
Journal: Journal of the American College of Cardiology (1995)