tbuckley/cabot-search huggingface dataset:
Abstract 1030: Arsenic trioxide plus ethacrynic acid-butyl ester is synergistic to induce apoptosis in myeloid leukemia cells through upregulation of NOXA
Authors: Rui Wang, Changda Liu, Samuel Waxman, Yongkui Jing
Journal: Cancer Research (2010)

Abstract Arsenic trioxide (As2O3) induces complete remission in acute promyelocytic leukemia (APL) patients. However, other types of myeloid leukemia patients are less responsive to As2O3 treatment. APL t(15;17) NB4 cells are more sensitive to As2O3 apoptosis induction than other types of myeloid leukemia cells such as HL-60 and K562 cells. Previously we reported that As2O3 induces apoptosis in NB4 cells through a reactive oxygen species (ROS)-mediated pathway which is attenuated by the expression of glutathione-s-transferase π (GSTπ). NB4 cells contain lower levels of GSTπ than other types of myeloid leukemia cells. Therefore, inhibition of GSTπ should enhance As2O3 induction of apoptosis in other types of myeloid leukemia cells. We investigated the combined effect of As2O3 with ethacrynic acid (EA) and a more potent non-diuretic EA analogue ethacrynic acid-butyl ester (EABE), known GSTπ inhibitors, to induce apoptosis in HL-60 and K562 cells. As2O3 at clinical achievable concentrations (1-2 µM) did not induce apoptosis in HL-60 cells nor in K562 cells. EA at a concentration lower than 60 μM did not induce apoptosis in both cell lines either. As2O3 at 2 μM plus EA at 60 μM are synergistic to induce apoptosis in both HL-60 and K562 cells as measured by Annexin V staining, PARP cleavage and caspase activation. More intriguing, EABE at 1 μM (60 fold lower than EA), which inhibits GSTπ activity, exhibited synergistic induction with As2O3 in K562 cells. Combined index of As2O3 with EABE to induce apoptosis in K562 cells calculated by CompuSyn software was less than 1.0 which indicated synergism. Apoptosis induction by the combination treatment of As2O3 with EABE correlated with the upregulation of the Bcl-2 homology 3 (BH3)-only pro-apoptotic protein NOXA. Knock-down of NOXA using siRNA blocked apoptosis induction of As2O3 plus EABE, while, knock-down of Mcl-1 enhanced the apoptosis induction of As2O3 plus EABE. Immunoprecipiation with Mcl-1 antibody revealed that NOXA bond to Mcl-1 in the K562 cells treated with As2O3 plus EABE. Inhibition of ROS production did not inhibit the upregulation of NOXA nor the apoptosis induction of As2O3 plus EABE treatment. Our data suggest that As2O3 plus EABE induce apoptosis through a novel mechanism which induces NOXA and sequesters Mcl-1 leading to the activation the intrinsic apoptotic pathway. 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 1030.
Control of the Na-Ca exchanger in isolated heart cells. I. Induction of Na-Na exchange in sodium-loaded cells by intracellular calcium.
Authors: R A Haworth, A B Goknur, D R Hunter
Journal: Circulation Research (1991)

Isolated adult rat heart cells in suspension were loaded with sodium by incubation with ouabain in the absence of calcium for 30 minutes. Addition of low levels of calcium induced accelerated rates of sodium influx and efflux, as measured with 22Na. The magnitude of calcium-induced 22Na efflux was 50-fold greater than the net rate of calcium uptake and required extracellular sodium, but not extracellular calcium, once some calcium was taken up. Calcium did not induce 86Rb efflux. The accelerated rate of 22Na efflux was prevented by verapamil, but verapamil was ineffective when added after calcium. Addition of EGTA after calcium reversed the effect of calcium, but only after incubation. Dichlorobenzamil, unlike verapamil, both prevented and reversed the induction of sodium fluxes by calcium. We conclude 1) that intracellular calcium induces Na-Na exchange through the Na-Ca exchanger in sodium-loaded cells exposed to calcium; and 2) that Na-Na exchange can be activated by calcium that enters the cell through calcium channels. We propose that this Na-Na exchange reflects the intrinsic activity of the Na-Ca exchanger.
Relative activity of beta-blockers.
Authors: B M Guyer
Journal: BMJ (1978)

eye injuries was in players aged 11 to 15 years.Largely as a result of this study and others like it protective headwear and facewear is now mandatory in almost all junior ice hockey in Canada.There have also been recent articles regarding eye injuries in badminton2 and squash.3I am not aware of such an article on cricket eye injuries.This is just the right time for such a survey.I write from the land of ice hockey to the land of cricket in the hope of stimulating somebody to tackle the sticky
Targeted Proteolysis Sustains Calcineurin Activation
Authors: Natalie Burkard, Jan Becher, Cornelia Heindl, Ludwig Neyses, Kai Schuh, Oliver Ritter
Journal: Circulation (2005)

Calcineurin (CnA) is important in the regulation of myocardial hypertrophy. We demonstrated that targeted proteolysis of the CnA autoinhibitory domain under pathological myocardial workload leads to increased CnA activity in human myocardium. Here, we investigated the proteolytic mechanism leading to activation of CnA.In patients with diseased myocardium, we found strong nuclear translocation of CnA. In contrast, in normal human myocardium, there was a cytosolic distribution of CnA. Stimulation of rat cardiomyocytes with angiotensin (Ang) II increased calpain activity significantly (433+/-11%; P<0.01; n=6) and caused proteolysis of the autoinhibitory domain of CnA. Inhibition of calpain by a membrane-permeable calpain inhibitor prevented proteolysis. We identified the cleavage site of calpain in the human CnA sequence at amino acid 424. CnA activity was increased after Ang II stimulation (310+/-29%; P<0.01; n=6) and remained high after removal of Ang II (214+/-17%; P<0.01; n=6). Addition of a calpain inhibitor to the medium decreased CnA activity (110+/-19%; P=NS; n=6) after removal of Ang II. Ang II stimulation of cardiomyocytes also translocated CnA into the nucleus as demonstrated by immunohistochemical staining and transfection assays with GFP-tagged CnA. Calpain inhibition and therefore suppression of calpain-mediated proteolysis of CnA enabled CnA exit from the nucleus.Ang II stimulation of cardiomyocytes increased calpain activity, leading to proteolysis of the autoinhibitory domain of CnA. This causes an increase in CnA activity and results in nuclear translocation of CnA. Loss of the autoinhibitory domain renders CnA constitutively nuclear and active, even after removal of the hypertrophic stimulus.
SO-CALLED TRAUMATIC DISPLACEMENTS OF THE UTERUS
Authors: HARRY E. MOCK
Journal: JAMA (1922)

The medical profession has been closely associated with the rapid industrial development of the United States during the last two decades—more closely than most physicians realize. Many great industries have awakened to the economic value of preserving their human machines. Formerly the human machine was used to the utmost, and, when broken, was thrown on the scrap heap; today, at least five states, as well as the federal government, have passed rehabilitation laws, with a view to salvaging the disabled employee and replacing him in industry as a productive unit of society. Forty-two states have passed employees' compensation laws; many of them are still inadequate, but all are for the purpose of paying the just claims of men disabled by their work. Thus the industrial world is filled with great medico-economic and medicolegal problems, whose solution depends primarily on the assistance of the leaders in the medical profession.  Industrial compensation
FROM SADDLEBAGS TO POCKETBOOKS.
Authors: B. T. WHITMORE
Journal: JAMA (1900)

Within the memory of men yet young it is not difficult to find the picture of the ancient physician, of the old type and taking a wholesome pride to himself as belonging to the old school, in fighting the battles of which he would expend a mighty polemical energy. He was an ornament to his profession, and his profession reflected honor on him. With the minister and the squire, the doctor formed the triumvirate of the American community, leaders of public opinion, foremost in all public works, the friends and advisers of all classes of society. There was then no opportunity for specialism nor for office practice. The old doctor was called to cover a wide district in his gig, more often on the back of an equally sedate horse, which had through long experience learned the doctor's calling list, even if not his method of treatment. But whether in
A taxonomy of generic clinical questions: classification study
Authors: John W Ely, Jerome A Osheroff, Paul N Gorman, Mark H Ebell, M Lee Chambliss, Eric A Pifer, P Zoe Stavri
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objective:</b> To develop a taxonomy of doctors9 questions about patient care that could be used to help answer such questions. <b>Design:</b> Use of 295 questions asked by Oregon primary care doctors to modify previously developed taxonomy of 1101 clinical questions asked by Iowa family doctors. <b>Setting:</b> Primary care practices in Iowa and Oregon. <b>Participants:</b> Random samples of 103 Iowa family doctors and 49 Oregon primary care doctors. <b>Main outcome measures:</b> Consensus among seven investigators on a meaningful taxonomy of generic questions; interrater reliability among 11 individuals who used the taxonomy to classify a random sample of 100 questions: 50 from Iowa and 50 from Oregon. <b>Results:</b> The revised taxonomy, which comprised 64 generic question types, was used to classify 1396 clinical questions. The three commonest generic types were "What is the drug of choice for condition x?" (150 questions, 11%); "What is the cause of symptom x?" (115 questions, 8%); and "What test is indicated in situation x?" (112 questions, 8%). The mean interrater reliability among 11 coders was moderate (κ=0.53, agreement 55%). <b>Conclusions:</b> Clinical questions in primary care can be categorised into a limited number of generic types. A moderate degree of interrater reliability was achieved with the taxonomy developed in this study. The taxonomy may enhance our understanding of doctors9 information needs and improve our ability to meet those needs.
A CLINICAL OBSERVATION OF NINETY CASES OF TYPHOID FEVER.WITH FOUR DEATHS, WITH SPECIAL REFERENCE TO THERAPEUTIC FASTING.
Authors: R. M. HARBIN
Journal: JAMA (1903)

While a statistical study of typhoid fever is not in strict accordance with the caption of this article, there is a valuable amount of information as to the etiology of the disease furnished by the vital statistics of the Twelfth Census Reports and, for a practical observation, a few facts may be referred to without impropriety. The geographical distribution of typhoid fever shows a greater prevalence in the southern states, including the Carolinas, Georgia, Alabama, Mississippi and Tennessee, the death rate being 76.1 per 1,000 deaths. Next highest mortality is 69.5 for Louisiana, Missouri, Arkansas, Indian Territory and Texas. Of the latter 80.6 is rural and 38.7 is cities. The general rate for rural is 48 and cities 19, which suggests a greater source of infection in the rural districts. Nearly every source of the infection can be excluded except the drinking water, which is contaminated by the soil. My
Mammography and Palpable Breast Abnormalities
Authors: Karla Kerlikowske
Journal: Annals of Internal Medicine (2004)

Letters4 May 2004Mammography and Palpable Breast AbnormalitiesKarla Kerlikowske, MDKarla Kerlikowske, MDFrom San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-9-200405040-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate Dr. Evans's correspondence and the opportunity to clarify the use of the term likelihood ratios in our paper. Likelihood ratios are being used more frequently by clinicians in clinical practice but are still not as familiar as the sensitivity and specificity of a diagnostic test. Sensitivity is calculated among diseased persons and specificity is calculated among nondiseased persons, whereas likelihood ratios are calculated using a given test result among diseased and nondiseased persons, as noted in the footnotes of our Tables 2, 3, and 5. As stated by Dr. Evans, the likelihood ratios reported in our ...References1. Kerlikowske K, Grady D, Barclay J, Sickles EA, Ernster V. Likelihood ratios for modern screening mammography. Risk of breast cancer based on age and mammographic interpretation. JAMA. 1996;276:39-43. [PMID: 8667537] CrossrefMedlineGoogle Scholar2. Sackett DL, Haynes RB, Tugwell P. Clinical Epidemiology: A Basic Science for Clinical Medicine. 2nd ed. Boston, MA: Little, Brown; 1991:119. Google Scholar Author, Article, and Disclosure InformationAffiliations: From San Francisco Veterans Affairs Medical Center, San Francisco, CA 94121. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoEvaluation of Abnormal Mammography Results and Palpable Breast Abnormalities Karla Kerlikowske , Rebecca Smith-Bindman , Britt-Marie Ljung , and Deborah Grady Mammography and Palpable Breast Abnormalities Arthur T. Evans Metrics 4 May 2004Volume 140, Issue 9Page: 764KeywordsBiopsyEpidemiologyInformation storage and retrievalLikelihood ratioMammographySpecificity ePublished: 4 May 2004 Issue Published: 4 May 2004 CopyrightCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Unintended consequences in the drive for zero
Authors: M. Klompas
Journal: Thorax (2009)

With pressure mounting from legislators, insurers and consumer advocates to drive ventilator-associated pneumonia (VAP) rates to zero, the article by Conway Morris and colleagues ( see page 516 ) in this issue of Thorax is a timely reminder that VAP rates are uncertain estimates rather than concrete measures of patient morbidity.1 Conway Morris and colleagues show that the reported VAP rate of an Intensive Care Unit (ICU) is heavily dependent upon its favoured diagnostic technique. ICUs that exclusively use bronchoalveolar lavage (BAL) to diagnose VAP are liable to report VAP rates that are 76% lower than those that exclusively use endotracheal aspirates. This laxity in the VAP definition confers a risk that some well-intended initiatives may decrease VAP rates yet provide little benefit to patients and perhaps even put some at risk.

Conway Morris and colleagues base their estimate of varying VAP rates upon the comparative yield of simultaneous BAL and endotracheal aspirate cultures taken from 53 critically ill patients with clinical syndromes suggestive of pneumonia. All patients had radiographic infiltrates, pyrexia or an abnormal leucocyte count, and clinical signs of chest infection such as increased volume or purulence of sputum, crepitations and deterioration in oxygenation. In these patients, there was a clear step function in culture results: 89% of endotracheal aspirate qualitative cultures were positive (defined as any growth), 51% of endotracheal quantitative cultures were positive (defined as ⩾106 colony-forming units (CFU)/ml), and 21% of BAL cultures were positive (defined as ⩾104 CFU/ml).

Each of these culture thresholds qualifies as VAP using the definitions of the Hospitals in Europe Link for Infection Control through Surveillance (HELICS) system. Consequently, depending upon one’s choice of diagnostic technique, measured VAP rates can vary fourfold. HELICS does assign different VAP codes to patients depending upon which culture technique and threshold was used …
Time Squared: Repeated Measures on Phylogenies
Authors: H. Guo, R. E. Weiss, X. Gu, M. A. Suchard
Journal: Molecular Biology and Evolution (2006)

Studies of gene expression profiles in response to external perturbation generate repeated measures data that generally follow nonlinear curves. To explore the evolution of such profiles across a gene family, we introduce phylogenetic repeated measures (PR) models. These models draw strength from 2 forms of correlation in the data. Through gene duplication, the family's evolutionary relatedness induces the first form. The second is the correlation across time points within taxonic units, individual genes in this example. We borrow a Brownian diffusion process along a given phylogenetic tree to account for the relatedness and co-opt a repeated measures framework to model the latter. Through simulation studies, we demonstrate that repeated measures models outperform the previously available approaches that consider the longitudinal observations or their differences as independent and identically distributed by using deviance information criteria as Bayesian model selection tools; PR models that borrow phylogenetic information also perform better than nonphylogenetic repeated measures models when appropriate. We then analyze the evolution of gene expression in the yeast kinase family using splines to estimate nonlinear behavior across 3 perturbation experiments. Again, the PR models outperform previous approaches and afford the prediction of ancestral expression profiles. To demonstrate PR model applicability more generally, we conclude with a short examination of variation in brain development across 4 primate species.
STUDIES ON INFECTION AND IMMUNITY IN EXPERIMENTAL TYPHOID FEVER
Authors: Sidney Gaines, Joseph G. Tully, William D. Tigertt
Journal: The Journal of Experimental Medicine (1960)

Chimpanzees recovered from typhoid fever induced by ingestion of large numbers of phage-type T S. typhosa were rechallenged approximately a year and a half later with a like number of a phage-type E1 strain. Control animals exhibited febrile responses, bacteriemia, and other significant laboratory and clinical findings, including increases in C-reactive protein levels and sedimentation rates. All of the previously infected and recovered chimpanzees were negative with respect to the aforementioned observations, and appeared to have resisted significant re-infection. On the other hand, recovery from typhoid fever induced by smaller numbers of S. typhosa failed to protect completely against rechallenge with larger numbers of these organisms. These findings indicate that chimpanzees recovered from typhoid fever may be protected against re-infection, even though the re-infecting organism is of a different phage type. Differences in the magnitude of the original and subsequent infecting inocula appear to influence the response to rechallenge.
Is golf enough.
Authors: A W Fowler
Journal: BMJ (1977)

Record Linkage Study in the mid-1960s.:Taking these facts into account it is clear that we should continue to accept the figures of Knowelden et al as an accurate statement of the age-specific incidence of fractures of the neck of the femur in Great Britain.Incidence rates and admission rates are both important statistics in the planning and development of health services.
Nonmyeloablative Transplantation
Authors: Yoshiyuki Takahashi, Richard W. Childs
Journal: Clinical Cancer Research (2004)

Abstract High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation has been explored as a method to enhance the efficacy of chemotherapy for advanced solid tumors. The failure of autologous hematopoietic stem cell transplantation to prolong survival in patients with metastatic solid tumors has sparked interest recently in studies exploring the potential of allogeneic hematopoietic stem cell transplantation for such patients. Allogeneic hematopoietic stem cell transplantation is widely accepted as a potent form of immunotherapy capable of curing patients with chemotherapy-refractory hematologic malignancies. However, it was not until the end of the 20th century that investigators initiated trials to test the potential of allogeneic hematopoietic stem cell transplantation as immunotherapy in malignancies of epithelial origin. Early pilot trials have established proof-of-principle that graft-versus-tumor effects can induce complete or partial remission in some treatment-refractory metastatic solid tumors. In this review, we discuss the rationale for pilot trials investigating the potential of nonmyeloablative allogeneic hematopoietic stem cell transplantation in advanced cytokine-refractory renal cancer, highlighting the preliminary success, limitations, and future clinical directions of this approach.
Effects of Alcohol and Fluvastatin on Lipid Metabolism and Hepatic Function
Authors: Jan W. Smit
Journal: Annals of Internal Medicine (1995)

To determine the effects of fluvastatin, a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, combined with moderate alcohol consumption on lipid profiles and hepatic function in patients with primary hypercholesterolemia.Randomized, placebo-controlled, crossover study.Lipid clinic of a university hospital.31 patients with primary hypercholesterolemia (low-density lipoprotein cholesterol levels > or = 4.2 mmol/L) who had previously received a lipid-lowering diet.After a dietary baseline period, 26 patients were randomly assigned to receive 6 weeks of treatment with either 1) fluvastatin, 40 mg/d, added to 20 g of ethanol and diluted to 20% with orange juice or 2) fluvastatin added to orange juice alone. After a 6-week washout period, the two groups crossed over.Plasma fluvastatin levels, lipid levels, and clinical variables were determined at the end of each treatment period.Six patients left the study prematurely. The remaining patients (15 men, 5 women; mean age +/- SD 49.1 +/- 14.5 years; mean body mass index +/- SD 24.5 +/- 2.2 kg/m2) completed the study. Fluvastatin, alone and combined with alcohol, resulted in similar decreases in levels of total cholesterol (22% and 23%, respectively; P < 0.001 when compared with baseline), low-density lipoprotein cholesterol (28% and 29%, respectively; P < 0.001 compared with baseline), and apolipoprotein B (17% and 20%, respectively; P < 0.001 compared with baseline). High-density lipoprotein cholesterol and triglyceride levels were not changed. Fluvastatin with alcohol resulted in a significantly greater area under the plasma concentration curve (23.4 +/- 4.7 compared with 18.2 +/- 3.2 x 10(3) ng.min/mL) and in a greater time to maximum concentration (187.5 +/- 16.6 min compared with 130.9 +/- 7.0 min) than fluvastatin alone. Terminal half-life tended to increase. No important adverse clinical effects were observed.Six weeks of daily, moderate alcohol consumption influenced the metabolism of fluvastatin but did not interfere with its lipid-lowering efficacy and had no adverse effects.