tbuckley/cabot-search huggingface dataset:
Abstract 2915: The oxidation state of DJ-1 determines the cell fate during oxidative stress triggered by Fenretinide (4-HPR): autophagy or apoptosis.
Authors: Ji Cao, Meidan Ying, Nan Xie, Jun Zhang, Xiaowen Liu, Qiaojun He, Bo Yang
Journal: Cancer Research (2013)

Abstract Increasing oxidative stress caused by many anti-cancer drugs is commonly accompanied with a switch from autophagy, a cyto-protective response, to apoptosis in cancer cells. However, the underlying mechanism of this process is still poorly understood. To address this we chose fenretinide (4-HPR) as the candidate drug since the major anti-cancer mechanism of this drug is reactive oxygen species (ROS) induction. We have shown previously and herein that 4-HPR-driven ROS induce the autophagy-apoptosis transition in a threshold manner in vitro and vivo. During this process, ASK1-regulated JNK1 or p38 signaling is response for 4-HPR-induced autophagy or apoptosis, respectively. Given ASK1 play a pivotal role in the selective activation of individual signaling, we further characterize the potential regulating unit of ASK1 by immunoprecipitation following LC/MS/MS analysis. Of note, DJ-1, a crucial antioxidant protein, is identified from a total of 7 fragments. We show that DJ-1 interacts with ASK-1 under moderate oxidative stress, but segregate from ASK-1 under lethal level of oxidative stress, suggesting DJ-1 may be a potent key regulator of autophagy-apoptosis transition. Interestingly, various oxidation statuses and the stability of homo-dimer formation of DJ-1 are highly related to different levels of intracellular oxidative stress. Moreover, we apply two kinds of artificial DJ-1 mutants at position C106 or E18 and further confirm that DJ-1 served as an oxidative sensor to determine the switch between autophagy and apoptosis triggered by 4-HPR. Hence, different oxidation state of DJ-1 modulates ASK-1-JNK1/p38 signaling activation to dictate the cellular response to oxidative stress: to autophagy or apoptosis. Citation Format: Ji Cao, Meidan Ying, Nan Xie, Jun Zhang, Xiaowen Liu, Qiaojun He, Bo Yang. The oxidation state of DJ-1 determines the cell fate during oxidative stress triggered by Fenretinide (4-HPR): autophagy or apoptosis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2915. doi:10.1158/1538-7445.AM2013-2915 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Phase III, Double-Blind, Randomized Study Comparing Lapatinib Plus Paclitaxel With Placebo Plus Paclitaxel As First-Line Treatment for Metastatic Breast Cancer
Authors: Angelo Di Leo, Henry L. Gomez, Zeba Aziz, Zanete Zvirbule, Jose Bines, Michael C. Arbushites, Stephanie F. Guerrera, Maria Koehler, Cristina Oliva, Steven H. Stein, Lisa S. Williams, Judy Dering, Richard S. Finn, Michael F. Press
Journal: Journal of Clinical Oncology (2008)

Purpose Lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER-2/ErbB2), is effective against HER-2–positive locally advanced or metastatic breast cancer (MBC). This phase III trial evaluated the efficacy of lapatinib in HER-2–negative and HER-2–uncharacterized MBC. Patients and Methods Women with MBC were randomly assigned to first-line therapy with paclitaxel 175 mg/m 2 every 3 weeks plus lapatinib 1,500 mg/d or placebo. A preplanned retrospective evaluation of HER-2 status was performed using fluorescence in situ hybridization and immunohistochemistry. The primary end point was time to progression (TTP); secondary end points were objective response rate (ORR), clinical benefit rate (CBR), event-free survival (EFS), and overall survival (OS). Results In the intent-to-treat population (n = 579), there were no significant differences in TTP, EFS, or OS between treatment arms, although differences in ORR and CBR were noted. In 86 HER-2–positive patients (15%), treatment with paclitaxel-lapatinib resulted in statistically significant improvements in TTP, EFS, ORR, and CBR compared with paclitaxel-placebo. No differences between treatment groups were observed for any end point in HER-2–negative patients. The most common adverse events were alopecia, rash, and diarrhea. The incidence of diarrhea and rash was significantly higher in the paclitaxel-lapatinib arm. The rate of cardiac events was low, and no difference was observed between treatment arms. Conclusion Patients with HER-2–negative or HER-2–untested MBC did not benefit from the addition of lapatinib to paclitaxel. However, first-line therapy with paclitaxel-lapatinib significantly improved clinical outcomes in HER-2–positive patients. Prospective evaluation of the efficacy and safety of this combination is ongoing in early and metastatic HER-2–positive breast cancer patients.
The Role of the Intermediate Cardiac Care Unit
Authors: Julian Frieden
Journal: JAMA (1976)

After the introduction of a 22-bed, monitored intermediate cardiac care unit (ICCU), cardiac care unit admissions increased by 15.7%. A further increase in patient admissions of 37% was permitted by direct admissions to the ICCU from the emergency room. The duration of the hospital stay of patients with acute myocardial infarct was shortened by three days. The success rate of cardiac resuscitation improved, and potentially serious arrhythmias were treated more promptly. Hospital costs were substantially reduced by the use of a convalescent unit for patients whose ICCU stay was uncomplicated. Concentration of cardiac patients and specialized staff and equipment permitted more efficient care. (<i>JAMA</i>235:816-818, 1976)
Neuromuscular involvement in pituitary gigantism.
Authors: C Lucey
Journal: BMJ (1972)

of the specialized tissue.He felt that for inhibition to occur it should be shown that the vagus nerve innervated the entire ventricular specialized network, and that acetyl- choline should be shown to suppress spon- taneous activity of ventricular Purkinje fibres.It would seem that these two conditions also require to be met with regard to vera- pamil and the human heart before the claims of Drs.Livesley and Oram can be justified.-I am, etc.,
Impact of <i>Burkholderia dolosa</i> on Lung Function and Survival in Cystic Fibrosis
Authors: Leslie A. Kalish, David A. Waltz, Mark Dovey, Gail Potter-Bynoe, Alexander J. McAdam, John J. LiPuma, Craig Gerard, Donald Goldmann
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Chronic infection with Burkholderia cepacia complex bacteria in cystic fibrosis is associated with accelerated decline in pulmonary function and increased mortality. Clinical implications of the recently characterized genomovar VI, B. dolosa, are unknown.Characterization of impact of B. dolosa on pulmonary function and mortality in cystic fibrosis.We compared patients chronically infected with B. dolosa (n = 31) with unmatched patients with B. multivorans (n = 24) and with age- and sex-matched control subjects without Burkholderia species (n = 58). We analyzed rates of pulmonary function decline (% predicted FEV(1)) using a random effects model assuming segmented linear trends. All available FEV(1) measurements from 5 yr (median, 4.8) before until 2.5 yr (median, 1.5) after the first positive culture for Burkholderia (reference date) were analyzed. Survival was compared using the Kaplan-Meier method and proportional hazards model.Baseline FEV(1) and rate of decline were similar in the cohorts. Decline in FEV(1) after the reference date accelerated in patients with B. dolosa (-2.3 percentage points/yr pre vs. -7.1 post, p = 0.002), but was unchanged in the B. multivorans and control patients (-2.3 vs. -0.8 post, p = 0.38, and -2.1 pre vs. -0.5 post, p = 0.20, respectively). The probability of dying within 18 mo of the reference date was 13, 7, and 3% for B. dolosa, B. multivorans, and control patients, respectively (B. dolosa vs. control hazard ratio, 10.8; 95% confidence interval, 1.3-92.8; p = 0.03).B. dolosa chronic infection in cystic fibrosis is associated with accelerated loss of lung function and decreased survival.
Adult precursor B-ALL with BCR/ABL gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expression
Authors: MD Tabernero, AM Bortoluci, I Alaejos, MC López-Berges, A Rasillo, R García-Sanz, M García, JM Sayagués, M González, G Mateo, JF San Miguel, A Orfao
Journal: Leukemia (2001)
Mechanism of Experimental Atrial Flutter
Authors: A. LANARI, A. LAMBERTINI, A. RAVIN
Journal: Circulation Research (1956)

The mechanism of atrial flutter induced by the local application of aconitine or by the Rosenblueth-Garcia Ramos method was studied in dogs. The results were analyzed from a pharmacologic and electrocardiographic point of view. It was concluded that aconitine-induced flutter is due to a single, rapidly firing ectopic focus and electrically-induced flutter to a circus movement. Although they can be differentiated electrocardiographically by means of direct cardiac leads, they cannot be differentiated by esophageal or limb leads.
Transforming Practice
Authors: Thomas Bodenheimer
Journal: New England Journal of Medicine (2008)

The editors asked several experts to share their perspectives on the crisis in U.S. primary care. Their articles, which address this crisis from six different angles, follow. We also brought the five U.S. contributors together for a roundtable discussion of the problems and potential solutions for training, practice, compensation, and systemic change. A video of the discussion and reader comments can be seen at www.nejm.org.Overstressed by large patient panels, many primary care practices are performing below par. In one study, patients explaining their problem to a physician were interrupted after an average of 23 seconds. Fifty percent of patients leave office visits not understanding what the physician has told them. It would take a primary care physician 18 hours per day to provide all recommended preventive and chronic care services to a typical patient panel. As a result, only half of evidence-based care is actually provided.1 These disturbing findings can be attributed primarily to the overburdened 15-minute clinician visit.Two solutions come to mind: . . .
A Controlled Study of Three Methods of Prophylaxis against Streptococcal Infection in a Population of Rheumatic Children
Authors: Alvan R. Feinstein, Harrison F. Wood, Jeanne A. Epstein, Angelo Taranta, Rita Simpson, Esther Tursky, Thomas Argyros, Julian Frieden, Raymond C. Haas, Ilse Hirschfeld, Arthur J. Lewis, Carlos Manso, Konrad Ulich
Journal: New England Journal of Medicine (1959)

ORAL and injectable agents are now being widely used to prevent streptococcal infections in patients who have had rheumatic fever.1 , 2 The choice of treatment has generally been made arbitrarily because the comparative effectiveness of the available agents has not been adequately determined in clinical trials. For statistically valid results, any trial studies would need to ensure that the prophylactic agents were given to groups of patients whose numbers were large enough to be adequately comparable in certain crucial aspects of their rheumatic background.A previous report presented the results of the first two years of observation on 405 patients in . . .
Celebrating Complementarity
Authors: Mahlon B. Hoagland
Journal: Annals of Internal Medicine (2003)

The 1950s witnessed prodigious growth in our knowledge of the chemical nature of the gene, the mechanisms by which the information inherent in its sequence of nucleotide units was conveyed to the cell's machinery for synthesizing proteins, and the mode of operation of that machinery. Watson and Crick raised the curtain by revealing the structure of DNA, notably the complementary pairing of the nucleotides in its twin chains. Identified with the new field of molecular biology, Crick defined and expanded the field of genetic information coding and led attempts to elucidate principles governing information translation into protein. On a parallel and complementary track, biochemistsnotably the group led by Paul Zamecnikwere working out the details of the mechanism of protein synthesis: how and where in the cell amino acids were energized, sequenced, and polymerized. These two approaches to closely related problems, separated by a considerable cultural gap, merged dramatically in 1956. Crick's thinking led him to postulate the existence of adaptorsshort chains of RNA nucleotide bases that, when linked to amino acids, might make the latter chemically recognizable to an RNA template by complementary pairing of their bases with those of the template. Simultaneously, the Zamecnik group discovered enzymes (amino acyl-tRNA synthetases) capable of energizing amino acids and, thence, attaching them to a hitherto unsuspected cellular RNA (transfer RNA). These RNA molecules, in turn, donated their bound amino acids to elongating protein chains on ribosomes, thus appearing to serve the function of adaptors.
Public Health Risks of Not Vaccinating Children
Authors: Rita Swan
Journal: JAMA (2001)

In 67% of the cases of measles in vaccinated children, the exposure source was unknown. It seems likely that many of these cases were related to importation, since most cases of measles are now traced to importation, according to the Centers for Disease Control and Prevention’s Pink Book. 2 The article implies that exemptors are causing injury to vaccinated individuals. In fact, the risk of serious permanent harm from contact with exemptors is minuscule (less than 1 in 1 billion, if the incidence of serious complications of measles is about 1 in 1000) and is not even estimated by the authors. Moreover, any risk imposed by exemptors on others is at least 2 orders of magnitude less than the risk they willingly assume themselves. Everyone imposes much greater risk on others in many other ways, such as by driving a car rather than using public transportation. Should society therefore forbid automobiles? The final decision concerning children’s medical care should be made by parents with the advice of their own physicians. This article provides no justification for abridging the right of parents and patients to decline giving informed consent to measles-mumps-rubella or pertussis vaccines.
Increased expression of <scp>IL</scp>‐19 in the epithelium of patients with chronic rhinosinusitis and nasal polyps
Authors: E. Pace, V. Scafidi, D. Di Bona, L. Siena, G. Chiappara, M. Ferraro, S. La Grutta, S. Gallina, R. Speciale, A. Ballacchino, C. Bachert, J. Bousquet, M. Gjomarkaj
Journal: Allergy (2012)

Abstract Background Chronic rhinosinusitis ( CRS ) is an inflammation of the nose and of the paranasal sinuses. The involvement of the respiratory epithelium in the mechanisms of CRS is poorly understood. Aims Among proteins expressed by nasal epithelial cells in CRS , IL ‐19 may have key functions. We here aimed to determine the expression and regulation of IL ‐19. Methods Nasal biopsies from normal subjects ( n = 12), subjects with CRS but without nasal polyps ( NP ) ( CRS s NP , n = 12) and with CRS with NP ( CRS w NP , n = 15) were collected. Human A sthma G ene A rray and real‐time PCR were used to evaluate gene expression, western blot analysis and immunohistochemistry for protein expression. Results for IL ‐19 were confirmed by real‐time PCR . The constitutive and stimulated ( LPS , TGF β) expression of IL ‐19 and cell proliferation were evaluated in a nasal epithelial cell line ( RPMI 2650). Results Human A sthma G ene A rray showed an increased IL ‐19 gene expression in NP from patients with CRS in comparison with normal subjects. Real‐time PCR confirmed the IL ‐19 m RNA up‐regulation in patients with CRS w NP and showed an up‐regulation of IL ‐19, at lower extent, in patients with chronic rhinosinusitis without nasal polyps ( CRS s NP ) in comparison with normal subjects. Western blot analysis confirmed that IL ‐19 is increased also at protein level in patients with CRS w NP in comparison with normal subjects. In NP , IL ‐19 is highly expressed in the metaplastic nasal epithelium when compared to normal or hyperplastic epithelium. LPS stimulation increased IL ‐19 expression, and recombinant IL ‐19 increased cell proliferation in nasal epithelial cells. Conclusions IL ‐19 is overexpressed in the epithelium in CRS w NP and increases epithelial cell proliferation.
Hemodynamic response to normovolemic polycythemia at rest and during exercise in dogs.
Authors: J Lindenfeld, J V Weil, V L Travis, L D Horwitz
Journal: Circulation Research (1985)

Very little is known about the influence of polycythemia on oxygen transport during exercise. We studied chronically instrumented dogs trained to run on a treadmill before and after their hematocrit had been increased by isovolemic exchange transfusion with packed red blood cells. With normovolemic polycythemia, cardiac output fell in a linear fashion as hematocrit was increased to 65%, but these changes were balanced by an increasing oxygen content resulting in constant systemic oxygen transport. Oxygen consumption was unchanged both at rest and during exercise after induction of polycythemia. To investigate the effect of polycythemia on oxygen transport further, we measured both mixed venous Po2 and lactate. Mixed venous Po2 increased and lactate remained unchanged both at rest and in exercising polycythemic dogs. Thus, we conclude that, in conscious animals, systemic oxygen transport is well preserved with increasing hematocrit to at least 65%.
Journalists accused of wrecking doctors' lives
Authors: Joanna Lyall
Journal: BMJ (2005)

They are guilty of “soul murder,” says professor 

J ournalists' pursuit of human interest stories can wreck doctors' lives and threaten patient care, according to Raymond Tallis, professor of geriatric medicine at Manchester University.

Speaking in London last week at a debate on standards of medical journalism, Professor Tallis said, “One of the most striking trends in recent years has been the increasing ease with which journalists smash the lives of doctors and ruin the reputation of hospitals.”

He criticised journalists' coverage of the organ retention issue at Alder Hey Children's Hospital, Liverpool ( BMJ 2001;322: 371>), saying that journalists had joined hands with lawyers, “opportunist politicians, and grieving parents, to transform what had hitherto been routine practice—organ retention—into a macabre ritual.”

Professor Tallis said, “The scale of what Dick van Velzen, the pathologist at the heart of the scandal, did was unacceptable but retention of organs was within the law” and within the ethical guidelines. He added, “This did not prevent endless hysterical, persecutory coverage with tabloids hounding doctors and managers.”

Professor Tallis, author of Hippocratic Oath s : Medicine and its Discontents , an analysis of modern medicine published last year ( BMJ …
Estimated Prevalence of Anabolic Steroid Use Among Male High School Seniors
Authors: William E. Buckley
Journal: JAMA (1988)

The use of anabolic-androgenic steroids (AS) is perceived by the media, by segments of the sports medicine and athletic communities, and by the public to have grown to epidemic proportions. Unfortunately, the incidence and prevalence of AS use among elite, amateur, and recreational athletes is poorly documented. This study was designed to help identify AS use patterns among the male portion of the general adolescent population. The overall participation rate on a schoolwide basis was 68.7% and on an individual basis reached 50.3%. Participants in this investigation were 12th-grade male students (N = 3403) in 46 private and public high schools across the nation who completed a questionnaire that established current or previous use of AS as well as user and nonuser characteristics. Results indicate that 6.6% of 12th grade male students use or have used AS and that over two thirds of the user group initiated use when they were 16 years of age or younger. Approximately 21% of users reported that a health professional was their primary source. The evidence indicates that educational intervention strategies should begin as early as junior high school; the intervention should not be directed only toward those individuals who participate in school-based athletics.
Reduced ribosomal protein gene dosage and p53 activation in low-risk myelodysplastic syndrome
Authors: Kelly A. McGowan, Wendy W. Pang, Rashmi Bhardwaj, Marcelina G. Perez, John V. Pluvinage, Bertil E. Glader, Reem Malek, Susan M. Mendrysa, Irving L. Weissman, Christopher Y. Park, Gregory S. Barsh
Journal: Blood (2011)
Comparisons of the molecular evolutionary process at rbcL and ndhF in the grass family (Poaceae)
Authors: B. S. Gaut, L. G. Clark, J. F. Wendel, S. V. Muse
Journal: Molecular Biology and Evolution (1997)

We examine rate heterogeneity among evolutionary lineages of the grass family at two plasmid loci, ndhF and rbcL, and we introduce a method to determine whether patterns of rate heterogeneity are correlated between loci. We show both that rates of synonymous evolution are heterogeneous among grass lineages and that are heterogeneity is correlated between loci at synonymous sites. At nonsynonymous sites, the pattern of rate heterogeneity is not correlated between loci, primarily due to an aberrant pattern of rate heterogeneity at nonsynonymous sites of rbcL. We compare patterns of synonymous rate heterogeneity to predictors based on the generation time effect and the speciation rate hypotheses. Although there is some evidence for generation time effects, neither generation time effects nor speciation rates appear to be sufficient to explain patterns of rate heterogeneity in the grass plastid sequences.
Primary Lymphomas of the Breast Detected by Ga-67 Scintigraphy
Authors: MITSURU KOIZUMI, AKIKO ARUGA, KEIKO YAMADA
Journal: Clinical Nuclear Medicine (1996)

Three patients with primary breast lymphoma are reported. All patients had rapidly growing breast masses and these masses showed nonspecific findings in mammography and on ultrasound. They resembled phyllodes tumor or invasive ductal carcinomas. Ga-67 scintigraphy showed intense accumulation was seen in all of the lymphomas. In one patient, a breast carcinoma was detected in the contralateral breast which did not show Ga-67 accumulation. In the other two patients, axillary involvement was also detected. Scintigraphy was helpful to confirm the diagnosis of breast lymphoma.
Evidence That the Age at Diagnosis of IDDM Is Genetically Determined
Authors: Danila Fava, Stephen Gardner, David Pyke, R David G Leslie
Journal: Diabetes Care (1998)

OBJECTIVE The aim of this study was to determine the impact of genetic or environmental factors on the age or time of onset of IDDM by studying pairs of twins and siblings concordant for the disease. RESEARCH DESIGN AND METHODS From 404 twin pairs referred to a diabetic twin study, we selected pairs concordant for IDDM: 1) 116 identical pairs with an index twin diagnosed diabetic under age 60 years and 2) 12 identical and 12 nonidentical matched twin pairs. From 972 families referred to a population-based diabetic family study, we selected sibling pairs with IDDM: 33 pairs with an index case diagnosed diabetic under age 21 years. Twin and sibling pairs were analyzed for intraclass correlations for age and time of diagnosis. RESULTS Of twins concordant for IDDM, the age at diagnosis correlated 1) in 116 identical pairs (R = 0.94; P &amp;lt; 0.000001) and 2) more closely in 12 identical twins (R = 0.96, P &amp;lt; 0.000001) than 12 nonidentical twins (R = 0.59, P = 0.046). Of 33 sibling pairs with IDDM, the age, but not the time, of diagnosis was correlated (R = 0.53, P = 0.0016). CONCLUSIONS Correlations within pairs of twins and siblings for age, not time, at diagnosis suggest that much of the variability of the age at diagnosis of IDDM is genetically determined.