tbuckley/cabot-search huggingface dataset:
Patterns of Locoregional Failure in Patients With Operable Breast Cancer Treated by Mastectomy and Adjuvant Chemotherapy With or Without Tamoxifen and Without Radiotherapy: Results From Five National Surgical Adjuvant Breast and Bowel Project Randomized Clinical Trials
Authors: Alphonse Taghian, Jong-Hyeon Jeong, Eleftherios Mamounas, Stewart Anderson, John Bryant, Melvin Deutsch, Norman Wolmark
Journal: Journal of Clinical Oncology (2004)

To assess patterns of locoregional failure (LRF) in lymph node-positive (LN+) breast cancer patients treated with mastectomy and adjuvant chemotherapy (+/- tamoxifen) and without postmastectomy radiotherapy (PMRT) in five National Surgical Adjuvant Breast and Bowel Project trials.We examined 5,758 patients enrolled onto the B-15, B-16, B-18, B-22, and B-25 trials. Median follow-up time was 11.1 years. Distribution of pathologic tumor size was < or = 2 cm, 2.1 to 5 cm, and more than 5 cm in 30%, 52%, and 11% of patients, respectively. Distribution of the number of LN+ was one to three, four to nine, and > or = 10 in 51%, 32%, and 16% of patients, respectively. Ninety percent of patients received doxorubicin-based chemotherapy.The overall 10-year cumulative incidences of isolated LRF, LRF with or without distant failure (DF), and DF alone as first event were 12.2%, 19.8%, and 43.3%, respectively. Cumulative incidences for LRF as first event with or without DF for patients with one to three, four to nine, and > or = 10 LN+ were 13.0%, 24.4%, and 31.9%, respectively (P < .0001). For patients with a tumor size of < or = 2 cm, 2.1 to 5.0 cm, and more than 5.0 cm, these incidences were 14.9%, 21.3%, and 24.6%, respectively (P < .0001). Multivariate analysis showed age, tumor size, premenopausal status, number of LN+, and number of dissected LN as significant predictors for LRF as first event.In patients with large tumors and four or more LN+, LRF as first event remains a significant problem. Although PMRT is currently recommended for patients with four or more LN+, it may also have value in selected patients with one to three LN+. However, in the absence of a randomized trial examining the worth of radiotherapy in this group of patients, the value of PMRT remains unknown.
ET-41 * TEMOZOLOMIDE CYTOTOXICITY IS POTENTIATED BY METABOLIC MODIFICATIONS IN GLIOBLASTOMA MULTIFORME (GBM)
Authors: S. Mukherjee, R. Tobin, S. Rogers, L. Dao, J. Kain, G. Dusio, S. Singel, E. Fonkem, M. K. Newell-Rogers
Journal: Neuro-Oncology (2014)

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumor with poor prognosis. Like other difficult-to-treat cancers, GBM utilizes glucose (glycolysis) at a high rate (the Warburg effect), but can adapt to stresses or starvation by using alternatives, including fatty acids or amino acids, as mitochondrial substrates. The unique features of GBM-specific metabolism may serve as novel therapeutic targets. Temozolomide (TMZ), along with surgery and radiation, are current standards for treating GBM. TMZ induces DNA damage, resulting in cell cycle arrest, and apoptosis. However, GBM can overcome TMZ by activating DNA repair enzymes. Our hypothesis is that combining TMZ with metabolic disrupting agents will potentiate TMZ cytotoxicity. To test this hypothesis, C6 (rat) and 263 (human) GBM cell lines were treated TMZ, with or without inhibitors of fatty acid oxidation or autophagy. Treated cells were stained and analyzed by flow cytometry for mitochondrial membrane potential (ΔΨ); uncoupling protein 2 (UCP2); Fas (CD95) and FasL (CD178); LC3A/B, detecting autophagy; and for DNA damage quantification. Explanted human GBM was stained for UCP2. We found that C6, 263, and explanted GBM tissue express significant levels of UCP2. In C6, etomoxir increased ΔΨ and decreased UCP2 expression. As predicted, etomoxir enhanced TMZ-induced DNA damage and the combination treatment elicited a greater response. Each treatment altered Fas and FasL expression, but the combination of etomoxir plus TMZ were necessary to achieve significant differences. Interestingly, we observed one high and one relatively low population of cells with regard to LC3A/B. However, treatment with etomoxir caused the largest increase in accumulation of LC3A/B, an indicator of autophagy. Finally, we determined the optimum combinations of combined drugs to achieve the greatest level of toxicity. We demonstrate that combination treatment using TMZ with metabolic inhibitors potentiates the effectiveness of TMZ on GBM.
Paradoxical Effects of Epinephrine on Excitation-Contraction Coupling in Cardiac Muscle
Authors: Frederic Kavaler, Martin Morad
Journal: Circulation Research (1966)

The possibility that the inotropic action of epinephrine might be mediated through an effect on the excitation-contraction coupling process was explored, using techniques for measurement of isometric tension, together, in some experiments, with recording of the transmembrane potential time course from short lengths of cat papillary muscle. Four observations relevant to this question, have been made: (1) Extracellular calcium concentration can be raised and extracellular sodium concentration lowered to a point at which contraction cannot be further augmented by the addition of epinephrine. (2) The early relaxation induced by epinephrine occurs well in advance of membrane repolarization. This effect is antagonized by increasing calcium concentration, although the action of epinephrine in augmenting developed tension appears to be synergistic with that of calciumion. (3) The length-tension relationship is undiminished in the calcium-rich (8.1 mmoles /liter), sodium-poor (75 mEq/liter) medium. (4) Epinephrine, in a dose (1 to 2 µg/ml) which markedly augments twitch tension, profoundly decreases tension developed by the same preparation during a potassium chloride contracture; this is the case for both the frog ventricle strip and the cat papillary muscle. A preliminary concept of the ionic mechanism of excitation-contraction coupling, compatible with these facts and with some others, is described.
Concurrent onset of adult onset Still's disease and insulin dependent diabetes mellitus.
Authors: J T Sibley
Journal: Annals of the Rheumatic Diseases (1990)

Within two weeks after symptoms of an upper respiratory tract infection a 32 year old man developed Still's disease and insulin dependent diabetes mellitus, both of which have persisted for 24 months. Investigations failed to confirm acute infection but did show isolated persistent increase of serum antibodies to rubella virus. The simultaneous onset of these two diseases suggests a shared cause, possible associated with rubella infection.
Association of Genetic Variants in Alcohol Dehydrogenase 4 With Alcohol Dependence in Brazilian Patients
Authors: Camila Guindalini, Sandra Scivoletto, Ricardo G.M. Ferreira, Gerome Breen, Monica Zilberman, Marco Aurélio Peluso, Mayana Zatz
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors evaluated the association of three functional promoter polymorphisms of the ADH4 gene with alcohol dependence. METHOD: DNA from 92 alcohol-dependent patients and 92 healthy comparison subjects was genotyped for all three polymorphisms. RESULTS: Variants at the –75 base-pair (bp) (C allele) and –159 bp (A allele) positions were associated with alcohol dependence. Individuals with haplotypes carrying both risk alleles showed an odds ratio of 2.9. CONCLUSIONS: These preliminary results suggest that ADH4 may play a role in the etiology of alcohol dependence. The association requires further study and replication but is functionally plausible and has a large effect size.
Ophelia (“And He Will Not Come Back Again”)
Authors: Janet M. Torpy
Journal: JAMA (2011)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Arginase, Prostaglandins, and Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma
Authors: Augusto C. Ochoa, Arnold H. Zea, Claudia Hernandez, Paulo C. Rodriguez
Journal: Clinical Cancer Research (2007)

Abstract Tumor-induced tolerance is a well-established phenomenon in cancer patients that can severely impair the therapeutic efficacy of immunotherapy. One mechanism leading to T-cell tolerance is the generation of myeloid-derived suppressor cells (MDSC) by soluble factors produced by the tumor. MDSC express CD11b+ as a common marker but may vary in their stage of maturation, depending on the tumor factors being produced. Arginase production by MDSC depletes arginine from the tumor microenvironment and impairs T-cell signal transduction and function. We studied whether an increase in MDSC could explain the molecular alterations and dysfunction found in T cells of patients with renal cell carcinoma (RCC). Arginase activity in the peripheral blood mononuclear cells of 117 RCC patients was increased between 6- to 8-fold compared with normal controls. The increased arginase activity was limited to the CD11b+CD14− myeloid cells and resulted in significantly decreased serum levels of arginine and increased ornithine in patients. Depletion of MDSC restored IFN-γ production and T-cell proliferation. Preliminary data suggest that prostaglandin E2 produced by the tumor induces arginase I expression in MDSC. Therefore, blocking MDSC activity may enhance the therapeutic efficacy of immunotherapy in RCC.
A Simulation Model Investigating the Impact of Tumor Volume Doubling Time and Mammographic Tumor Detectability on Screening Outcomes in Women Aged 40–49 Years
Authors: Stephanie L. Bailey, Bronislava M. Sigal, Sylvia K. Plevritis
Journal: JNCI Journal of the National Cancer Institute (2010)

Compared with women aged 50-69 years, the lower sensitivity of mammographic screening in women aged 40-49 years is largely attributed to the lower mammographic tumor detectability and faster tumor growth in the younger women.We used a Monte Carlo simulation model of breast cancer screening by age to estimate the median tumor size detectable on a mammogram and the mean tumor volume doubling time. The estimates were calculated by calibrating the predicted breast cancer incidence rates to the actual rates from the Surveillance, Epidemiology, and End Results (SEER) database and the predicted distributions of screen-detected tumor sizes to the actual distributions obtained from the Breast Cancer Surveillance Consortium (BCSC). The calibrated parameters were used to estimate the relative impact of lower mammographic tumor detectability vs faster tumor volume doubling time on the poorer screening outcomes in younger women compared with older women. Mammography screening outcomes included sensitivity, mean tumor size at detection, lifetime gained, and breast cancer mortality. In addition, the relationship between screening sensitivity and breast cancer mortality was investigated as a function of tumor volume doubling time, mammographic tumor detectability, and screening interval.Lowered mammographic tumor detectability accounted for 79% and faster tumor volume doubling time accounted for 21% of the poorer sensitivity of mammography screening in younger women compared with older women. The relative contributions were similar when the impact of screening was evaluated in terms of mean tumor size at detection, lifetime gained, and breast cancer mortality. Screening sensitivity and breast cancer mortality reduction attributable to screening were almost linearly related when comparing annual or biennial screening with no screening. However, when comparing annual with biennial screening, the greatest reduction in breast cancer mortality attributable to screening did not correspond to the greatest gain in screening sensitivity and was more strongly affected by the mammographic tumor detectability than tumor volume doubling time.The age-specific differences in mammographic tumor detection contribute more than age-specific differences in tumor growth rates to the lowered performance of mammography screening in younger women.
Cardiopulmonary responses to exercise in pediatric thalassemia following hematopoietic stem cell transplantation vs. intensified transfusion
Authors: Prapaporn Pornsuriyasak, Jittamas Chokechuleekorn, Suradej Hongeng, Samart Pakakasama, Ampaiwan Ampaiwan, Aroonwan Preutthipan, Supattra Kiewwan
Journal: European Respiratory Journal (2014)

Background : Cardiopulmonary performance during exercise has been persistently impaired in children with thalassemia (TM) after hematopoietic stem cell transplantation (HSCT) and in those without transplantation (non-HSCT). We aimed to compare these responses between TM patients undergone HSCT for over 5 years and non-HSCT patients treated with intensified transfusion.   Methods : Ten TM patients undergone HSCT over 5 years, 9 non-HSCT TM patients treated with intensified transfusion, and 11 healthy age-, and gender-matched subjects (aged 8-12, and ≥ 13 years old) having normal spirometry were prospectively examined. Symptom-limited incremental cardiopulmonary exercise testing on a cycle ergometry was performed. Oxygen uptake (VO2), heart rate (HR), anaerobic threshold (AT), and ventilation (VE) were measured. The oxygen cost of work (ΔVo2/ΔWR), and the slope of HR as a response to VO2 (ΔHR/ΔVO2) were calculated.   Results : The duration following HSCT was 7.9±2.3 years. The hematocrit levels in HSCT TM group were higher than in non-HSCT TM group (39.7±4.1 vs. 33.8±3.1%, p=0.003). There were no differences in peak VO2, peak HR, oxygen pulse, ΔVo2/ΔWR, and ΔHR/ΔVO2 among TM groups, compared to healthy controls in both age groups. Of those aged ≥13 years old, AT was lower in HSCT than in non-HSCT group and in healthy subjects (55.5±1.4%, 62.0±1.8%, and 67.2±5.9% of peak VO2, respectively, p=0.034).   Conclusion : Exercise capacity was not different among TM patients undergone HSCT over 5 years and treated with intensified transfusion, comparable to healthy controls. Nonetheless, impaired oxygen delivery was still evident in TM patients following HSCT.
Proteomic Identification of a Direct Role for Cyclin D1 in DNA Damage Repair
Authors: Siwanon Jirawatnotai, Yiduo Hu, David M. Livingston, Piotr Sicinski
Journal: Cancer Research (2012)

The human CCND1 gene, which encodes the cell-cycle protein cyclin D1, is one of the most frequently amplified genes in human cancers. Cyclin D1 activates the cyclin-dependent kinases CDK4 and CDK6 and drives cell proliferation. Beyond the cell-cycle role, the full repertoire of cyclin D1 functions in cancer cells is still unclear. Emerging evidence indicates that cyclin D1 may play a role in DNA damage response. In this review, we discuss observations linking cyclin D1 to DNA damage repair and summarize our recent findings, which show a cyclin D1 function in homologous recombination-mediated DNA repair.
Expression of ICOS In Vivo Defines CD4+ Effector T Cells with High Inflammatory Potential and a Strong Bias for Secretion of Interleukin 10
Authors: Max Löhning, Andreas Hutloff, Tilmann Kallinich, Hans Werner Mages, Kerstin Bonhagen, Andreas Radbruch, Eckard Hamelmann, Richard A. Kroczek
Journal: The Journal of Experimental Medicine (2003)

The studies performed to date analyzed the overall participation of the inducible costimulator (ICOS) in model diseases, but did not yield information on the nature and function of ICOS-expressing T cells in vivo. We examined ICOS+ T cells in the secondary lymphoid organs of nonmanipulated mice, in the context of an “unbiased” immune system shaped by environmental antigens. Using single cell analysis, ICOSlow cells were found to be loosely associated with the early cytokines interleukin (IL)-2, IL-3, IL-6, and interferon (IFN)-γ. ICOSmedium cells, the large majority of ICOS+ T cells in vivo, were very tightly associated with the synthesis of the T helper type 2 (Th2) cytokines IL-4, IL-5, and IL-13, and these cells exhibited potent inflammatory effects in vivo. In contrast, ICOShigh T cells were highly and selectively linked to the anti-inflammatory cytokine IL-10. Overall, these data seem to indicate that ICOS cell surface density serves as a regulatory mechanism for the release of cytokines with different immunological properties. Further in vivo functional experiments with in vitro–activated T cells strongly suggested that the ICOS+ population, although representing in vivo only around 10% of T cells bearing early or late activation markers, nevertheless encompasses virtually all effector T cells, a finding with major diagnostic and therapeutic implications.
Serum concentrations of P-selectin decline rapidly in resting humans
Authors: David A Scott
Journal: British Journal of Sports Medicine (2000)

Bone density in elderly womenEDITOR,-In the article by Rhodes et al 1 "EVects of one year of resistance training on the relation between muscular strength and bone density in elderly women", I was surprised to see no mention of HRT status in the women in the trial.Given the relatively small number of women taking part, surely this is quite an important variable?
Sport medicine research needs funding: the International football federations are leading the way
Authors: Jan Ekstrand, Jiri Dvorak, Michel D'Hooghe
Journal: British Journal of Sports Medicine (2013)

This issue of the BJSM contains 10 injury surveillance articles concentrated on the world's largest and most popular sport, football. As presented by Bizzini et al , football is played by almost 300 million people—or around 4% of the world's population.1 

From a medical perspective, football contains many positive motivational and social factors that may facilitate compliance and contribute to the maintenance of a physically active lifestyle.2 ,3 Recently, Krustrup et al demonstrated that football training for 2–3 h/week resulted in significant cardiovascular, metabolic and musculoskeletal adaptations, independent of gender, age or lack of experience with football.3 They conclusively showed that football provides broad-spectred health and fitness effects that are at least as pronounced as for running, and in some cases even better.3 

Despite the positive effects of participating in football and other sports, negative factors, such as the risk of injury, must also be considered. Such a risk is especially pronounced at the elite level, where football is a profession. And this is not a small group; according to FIFPro, the worldwide representative organisation for all professional players, there are more more than 50 000 professional players (http://fifpro.org/about).

The risk of injury in professional football has been estimated at about 1000 times greater than for typical industrial occupations generally regarded as high risk.4 As demonstrated by Ekstrand et al in this issue, the overall injury rate is around eight time-loss injuries per 1000 h …
Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study
Authors: W M Zapol, M T Snider, J D Hill, R J Fallat, R H Bartlett, L H Edmunds, A H Morris, E C Peirce nd, A N Thomas, H J Proctor, P A Drinker, P C Pratt, A Bagniewski, R G Miller
Journal: JAMA (1979)

Nine medical centers collaborated in a prospective randomized study to evaluate prolonged extracorporeal membrane oxygenation (ECMO) as a therapy for severe acute respiratory failure (ARF). Ninety adult patients were selected by common criteria of arterial hypoxemia and treated with either conventional mechanical ventilation (48 patients) or mechanical ventilation supplemented with partial venoarterial bypass (42 patients). Four patients in each group survived. The majority of patients suffered acute bacterial or viral pneumonia (57%). All nine patients with pulmonary embolism and six patients with posttraumatic acute respiratory failure died. The majority of patients died of progressive reduction of transpulmonary gas exchange and decreased compliance due to diffuse pulmonary inflammation, necrosis, and fibrosis. We conclude that ECMO can support respiratory gas exchange but did not increase the probability of long-term survival in patients with severe ARF. (<i>JAMA</i>242:2193-2196, 1979)
Response to Comment on Tone et al. Six-Week Versus Twelve-Week Antibiotic Therapy for Nonsurgically Treated Diabetic Foot Osteomyelitis: A Multicenter Open-Label Controlled Randomized Study. Diabetes Care 2015;38:302–307
Authors: Eric Senneville, Alina Tone, Michel Valette, Sophie Nguyen
Journal: Diabetes Care (2015)

We thank Nijenhuis-Rosien et al. for their comments (1) on our article (2). We thank them for their kind compliment and interesting questions and for giving us the opportunity to provide some additional information on our study.

First, we agree that off-loading of the foot ulcer is of paramount importance in patients with diabetic foot ulcer. The methods used for pressure off-loading in the five investigating centers that participated in the study were similar from one center …
Words failed me
Authors: L. Farrell
Journal: BMJ (1999)

When you English first came to Ireland you despoiled our relics, cut down all our ancient trees, pillaged our women, and made rude noises at our menfolk. But we got the better of you; we loved, relentlessly, every second of it, and as a bonus we got the English language, the heritage of Shakespeare and Milton, with all its capacity for bombast and subtlety, pageantry, and nuance, a star crossed marriage of a people gifted with a wild imagination …
Transcriptional role of p53 in interferon-mediated antiviral immunity
Authors: César Muñoz-Fontela, Salvador Macip, Luis Martínez-Sobrido, Lauren Brown, Joseph Ashour, Adolfo García-Sastre, Sam W. Lee, Stuart A. Aaronson
Journal: The Journal of Experimental Medicine (2008)

Tumor suppressor p53 is activated by several stimuli, including DNA damage and oncogenic stress. Previous studies (Takaoka, A., S. Hayakawa, H. Yanai, D. Stoiber, H. Negishi, H. Kikuchi, S. Sasaki, K. Imai, T. Shibue, K. Honda, and T. Taniguchi. 2003. Nature. 424:516–523) have shown that p53 is also induced in response to viral infections as a downstream transcriptional target of type I interferon (IFN) signaling. Moreover, many viruses, including SV40, human papillomavirus, Kaposi's sarcoma herpesvirus, adenoviruses, and even RNA viruses such as polioviruses, have evolved mechanisms designated to abrogate p53 responses. We describe a novel p53 function in the activation of the IFN pathway. We observed that infected mouse and human cells with functional p53 exhibited markedly decreased viral replication early after infection. This early inhibition of viral replication was mediated both in vitro and in vivo by a p53-dependent enhancement of IFN signaling, specifically the induction of genes containing IFN-stimulated response elements. Of note, p53 also contributed to an increase in IFN release from infected cells. We established that this p53-dependent enhancement of IFN signaling is dependent to a great extent on the ability of p53 to activate the transcription of IFN regulatory factor 9, a central component of the IFN-stimulated gene factor 3 complex. Our results demonstrate that p53 contributes to innate immunity by enhancing IFN-dependent antiviral activity independent of its functions as a proapoptotic and tumor suppressor gene.