tbuckley/cabot-search huggingface dataset:
Endoplasmic reticulum stress: cell life and death decisions
Authors: C. Xu
Journal: Journal of Clinical Investigation (2005)

Disturbances in the normal functions of the ER lead to an evolutionarily conserved cell stress response, the unfolded protein response, which is aimed initially at compensating for damage but can eventually trigger cell death if ER dysfunction is severe or prolonged. The mechanisms by which ER stress leads to cell death remain enigmatic, with multiple potential participants described but little clarity about which specific death effectors dominate in particular cellular contexts. Important roles for ER-initiated cell death pathways have been recognized for several diseases, including hypoxia, ischemia/reperfusion injury, neurodegeneration, heart disease, and diabetes.
Assessment of Myocardial Viability With <sup>99m</sup> Tc Sestamibi in Patients Undergoing Cardiac Transplantation
Authors: Rafael Medrano, Richard W. Lowry, James B. Young, Donald G. Weilbaecher, Lloyd H. Michael, Imran Afridi, Zuo-Xiang He, John J. Mahmarian, Mario S. Verani
Journal: Circulation (1996)

99mTc sestamibi and 201 Tl are tracers that allow equivalent detection of myocardial infarction. However, because sestamibi does not undergo as much time-dependent redistribution as does 201Tl, it has been considered suboptimal for the detection of myocardial viability.Fifteen consecutive patients with ischemic cardiomyopathy who underwent orthotopic cardiac transplantation received an intravenous injection of 99mTc sestamibi at 1 to 6 hours before transplantation. Rotational tomography of the excised, intact, native hearts was performed to quantify the extent of myocardial hypoperfusion. The hearts were then sliced and reimaged on a gamma camera, followed by pathological quantification of the extent and severity of scarred and normal myocardium. Samples of normally and abnormally perfused myocardium underwent gamma well counting to determine tissue radioactivity and were examined under light microscopy for delineation of myocardial structure after trichrome staining. The mean extent of scintigraphic scar quantified through the use of rotational tomography was 45 +/- 14% of the left ventricle and correlated closely with pathological scar size (r = .89), despite a slight overestimation. Scintigraphic scar size determined with planar imaging of the individual myocardial slices also correlated closely with pathological scar size (r = .88). A good correlation existed between tissue 99mTc sestamibi activity determined through well counting and histological evidence of myocardial viability (r = .89). Most hypokinetic and 40% of akinetic/dyskinetic myocardial segments contained scintigraphically and histologically normal myocardium.99mTc sestamibi scintigraphy can be used to accurately quantify the extent of myocardial scarring. Furthermore, the relative sestamibi activity in perfusion defects, measured several hours after administration, is a good indicator of myocardial viability determined with microscopy.
Breast Cancer Trends Among Black and White Women in the United States
Authors: Ismail Jatoi, William F. Anderson, Sowmya R. Rao, Susan S. Devesa
Journal: Journal of Clinical Oncology (2005)

Overall US breast cancer mortality rates are higher among black women than white women, and the disparity is widening. To investigate this disparity, we examined incidence data and changes in mortality trends according to age, year of death (calendar period), and date of birth (birth cohort). Calendar period mortality trends reflect the effects of new medical interventions, whereas birth cohort mortality trends reflect alterations in risk factors.Incidence data were obtained from the Connecticut and National Cancer Institute Surveillance, Epidemiology, and End Results registries and mortality data were obtained from the National Center for Health Statistics. Changes in age, period, and cohort mortality trends were analyzed with Poisson regression.For both races, breast cancer incidence rates for localized and regional disease diverged in the late 1970s. Almost concurrently, overall mortality rates diverged among blacks and whites. For both races, mortality increases with age, but blacks have higher mortality at age younger than 57. The calendar period curves revealed declining mortality for whites over the entire study period. For blacks, calendar period mortality declined until the late 1970s, and then sharply increased. After 1994, calendar period mortality declined for both. For women born between 1872 and 1950, trends in mortality were similar for blacks and whites. For women born after 1950, mortality decreased more rapidly for blacks.The widening racial disparity in breast cancer mortality seems attributable to calendar period rather than birth cohort effects. Thus, differences in response or access to newer medical interventions may largely account for these trends.
Transcriptional Functionality of Germ Line p53 Mutants Influences Cancer Phenotype
Authors: Paola Monti, Yari Ciribilli, Jennifer Jordan, Paola Menichini, David M. Umbach, Michael A. Resnick, Lucio Luzzatto, Alberto Inga, Gilberto Fronza
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The TP53 tumor suppressor gene encodes a sequence-specific transcription factor that is able to transactivate several sets of genes, the promoters of which include appropriate response elements. Although human cancers frequently contain mutated p53, the alleles as well as the clinical expression are often heterogeneous. Germ line mutations of TP53 result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni–like, and nonsyndromic predisposition with or without family history. p53 mutants can be classified as partial deficiency alleles or severe deficiency alleles depending on their ability to transactivate a set of human target sequences, as measured using a standardized yeast-based assay (see http://www.umd.be:2072/index.html). We have investigated the extent to which the functional features of p53 mutant alleles determine clinical features in patients who have inherited these alleles and have developed cancer. Experimental Design: We retrieved clinical data from the IARC database (see http://www.p53.iarc.fr/Germline.html) for all cancer patients with germ line p53 mutations and applied stringent statistical evaluations to compare the functional classification of p53 alleles with clinical phenotypes. Results: Our analyses reveal that partial deficiency alleles are associated with a milder family history (P = 0.007), a lower numbers of tumors (P = 0.007), and a delayed disease onset (median, 31 versus 15 years; P = 0.007) which could be related to distinct tumor spectra. Conclusions: These findings establish for the first time significant correlations between the residual transactivation function of individual TP53 alleles and clinical variables in patients with inherited p53 mutations who develop cancer.
Emergency Duties and Deaths from Heart Disease among Firefighters in the United States
Authors: Stefanos N. Kales, Elpidoforos S. Soteriades, Costas A. Christophi, David C. Christiani
Journal: New England Journal of Medicine (2007)

Heart disease causes 45% of the deaths that occur among U.S. firefighters while they are on duty. We examined duty-specific risks of death from coronary heart disease among on-duty U.S. firefighters from 1994 to 2004.We reviewed summaries provided by the Federal Emergency Management Agency of the deaths of all on-duty firefighters between 1994 and 2004, except for deaths associated with the September 11, 2001, terrorist attacks. Estimates of the proportions of time spent by firefighters each year performing various duties were obtained from a municipal fire department, from 17 large metropolitan fire departments, and from a national database. Odds ratios and 95% confidence intervals for death from coronary heart disease during specific duties were calculated from the ratios of the observed odds to the expected odds, with nonemergency duties as the reference category.Deaths from coronary heart disease were associated with suppressing a fire (32.1% of all such deaths), responding to an alarm (13.4%), returning from an alarm (17.4%), engaging in physical training (12.5%), responding to nonfire emergencies (9.4%), and performing nonemergency duties (15.4%). As compared with the odds of death from coronary heart disease during nonemergency duties, the odds were 12.1 to 136 times as high during fire suppression, 2.8 to 14.1 times as high during alarm response, 2.2 to 10.5 times as high during alarm return, and 2.9 to 6.6 times as high during physical training. These odds were based on three estimates of the time that firefighters spend on their duties.Certain emergency firefighting duties were associated with a risk of death from coronary heart disease that was markedly higher than the risk associated with nonemergency duties. Fire suppression was associated with the highest risk, which was approximately 10 to 100 times as high as that for nonemergency duties.
Macrophages from patients with SLE and rheumatoid arthritis have defective adhesion in vitro, while only SLE macrophages have impaired uptake of apoptotic cells
Authors: S W Tas
Journal: Annals of the Rheumatic Diseases (2005)

<b>Background:</b> It has been suggested that defective handling of apoptotic cells by macrophages plays a key role in the development of systemic lupus erythematosus (SLE). The relative contribution of intrinsic defects and serum factors remains controversial. <b>Objective:</b> To compare monocytes from SLE patients, patients with rheumatoid arthritis, and healthy controls for their ability to differentiate in vitro into macrophages and to bind/engulf apoptotic cells. <b>Methods:</b> Peripheral blood derived monocytes from healthy donors or from patients with SLE or rheumatoid arthritis were allowed to differentiate into macrophages. The in vitro uptake of apoptotic cells by macrophages was evaluated by a flow cytometry assay that allowed discrimination between binding and internalisation. <b>Results:</b> Monocytes from SLE and rheumatoid patients showed a striking defect in adherence to plastic compared with healthy donors. Absence or heat inactivation of serum resulted in a reduction in the binding and engulfment of apoptotic cells by macrophages. Macrophages from rheumatoid and SLE patients had similar percentages of apoptotic cells bound to their surface compared with normal controls. However, macrophages from SLE patients showed a significant defect in the internalisation of apoptotic cells compared with those from healthy controls, even in the presence of normal human serum. <b>Conclusions:</b> Monocytes from patients with SLE and rheumatoid arthritis have a similar defect in their capacity to adhere to plastic. However, only macrophages from SLE patients showed an impaired ability to engulf apoptotic cells, which indicates that an intrinsic cellular defect may be responsible for this phenomenon.
A suppressor T cell of the mixed lymphocyte reaction in man specific for the stimulating alloantigen. Evidence that identity at HLA-D between suppressor and responder is required for suppression.
Authors: E G Engleman, A J McMichael, M E Batey, H O McDevitt
Journal: The Journal of Experimental Medicine (1978)

It has previously been shown that J.H., a human leukocyte antigen (HLA)-Dw2 homozygous multiparous woman, fails to respond in a mixed lymphocyte reaction (MLR) to her Dw1 homozygous husband W.H., and that her T cells suppress the responses of HLA matched responders to W.H. The present studies take advantage of the observation that J.H. suppressor cells resist a dose of gamma-irradiation which functionally eliminates her MLR responder cells. J.H. cells, depleted of alloreactive cells, suppress the responses of Dw2 heterozygous or homozygous cells to W.H., regardless of their associated HLA-A or B antigens. Only when W.H. or a few other cells are present as the irradiated stimulator is J.H. suppression of Dw2 responses detected. Thus, the J.H. suppressor T cell recognizes determinants in the irradiated stimulator cells as well as D locus products in the responder.
Mature Results of an Individualized Radiation Dose Prescription Study Based on Normal Tissue Constraints in Stages I to III Non–Small-Cell Lung Cancer
Authors: Angela van Baardwijk, Stofferinus Wanders, Liesbeth Boersma, Jacques Borger, Michel Öllers, Anne-Marie C. Dingemans, Gerben Bootsma, Wiel Geraedts, Cordula Pitz, Ragnar Lunde, Philippe Lambin, Dirk De Ruysscher
Journal: Journal of Clinical Oncology (2010)

We previously showed that individualized radiation dose escalation based on normal tissue constraints would allow safe administration of high radiation doses with low complication rate. Here, we report the mature results of a prospective, single-arm study that used this individualized tolerable dose approach.In total, 166 patients with stage III or medically inoperable stage I to II non-small-cell lung cancer, WHO performance status 0 to 2, a forced expiratory volume at 1 second and diffusing capacity of lungs for carbon monoxide >or= 30% were included. Patients were irradiated using an individualized prescribed total tumor dose (TTD) based on normal tissue dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8 Gy fractions twice daily. Only sequential chemoradiation was administered. The primary end point was overall survival (OS), and the secondary end point was toxicity according to Common Terminology Criteria of Adverse Events (CTCAE) v3.0.The median prescribed TTD was 64.8 Gy (standard deviation, +/- 11.4 Gy) delivered in 25 +/- 5.8 days. With a median follow-up of 31.6 months, the median OS was 21.0 months with a 1-year OS of 68.7% and a 2-year OS of 45.0%. Multivariable analysis showed that only a large gross tumor volume significantly decreased OS (P < .001). Both acute (grade 3, 21.1%; grade 4, 2.4%) and late toxicity (grade 3, 4.2%; grade 4, 1.8%) were acceptable.Individualized prescribed radical radiotherapy based on normal tissue constraints with sequential chemoradiation shows survival rates that come close to results of concurrent chemoradiation schedules, with acceptable acute and late toxicity. A prospective randomized study is warranted to further investigate its efficacy.
Epidemiology of<i>Burkholderia cepacia</i>complex colonisation in cystic fibrosis patients
Authors: K. De Boeck, A. Malfroot, L. Van Schil, P. Lebecque, C. Knoop, J.R.W. Govan, C. Doherty, S. Laevens, P. Vandamme
Journal: European Respiratory Journal (2004)

In Belgian cystic fibrosis (CF) clinics, sputum samples are evaluated on selective MAST medium routinely every 3 months. In this study, in 1993 and 1999, isolates were further examined by recA restriction fragment length polymorphism analysis and pulsed-field gel electrophoresis of genomic DNA restricted with SpeI . In 1993, 12 patients were colonised with Burkholderia cepacia complex (Bcc): B. cenocepacia (n=6), B. multivorans (n=3), B. stabilis (n=3). Four patients were colonised with the same B. cenocepacia strain; two with the same B. stabilis strain. After 5 yrs, three B. cenocepacia - and one B. multivorans -colonised patients had died. In 1999, Bcc was isolated in 12 patients: B. multivorans (n=9), B. stabilis (n=1) and B. cenocepacia (n=2). Three patients were colonised by the same B. multivorans strain. Compared to matched controls, the 5 yr outcome was poor; four B. cepacia patients died and none of the control patients died. Lung-function evolution was poor. In conclusion, the rate of colonisation in Belgian cystic fibrosis patients is stable and low. Burkholderia cenocepacia was most prevalent in 1993; Burkholderia multivorans in 1999. The cross-infection rate is low. Three patients had transient colonisation. The impact of Burkholderia cepacia complex on morbidity in the Belgian cystic fibrosis population is high and not limited to Burkholderia cenocepacia .
Compensatory Pathways in Oncogenic Kinase Signaling and Resistance to Targeted Therapies: Six Degrees of Separation
Authors: Livio Trusolino, Andrea Bertotti
Journal: Cancer Discovery (2012)

Abstract Summary: The efficacy of targeted therapies against mutationally activated kinases is typically limited by the engagement of growth-promoting cues that compensate for inhibition of the targeted kinase. Initial studies have highlighted the contribution of genomic alterations, functional characteristics, and signaling feedback loops—all intrinsic to cancer cells—in sustaining such substitute activities. New evidence now indicates that the relative expression of growth factor ligands produced by the tumor microenvironment can relay redundant survival pathways, which may broadly impair responsiveness to kinase inhibitors. Cancer Discov; 2(10); 876–80. ©2012 AACR.
Changes in gene expression of granulocytes during in vivo granulocyte colony-stimulating factor/dexamethasone mobilization for transfusion purposes
Authors: Agata Drewniak, Bram J. van Raam, Judy Geissler, Anton T.J. Tool, Olaf R.F. Mook, Timo K. van den Berg, Frank Baas, Taco W. Kuijpers
Journal: Blood (2009)
Comparison of Doppler ultrasound velocity measurements with pressure differences across bioprosthetic valves in a pulsatile flow model
Authors: I A SIMPSON, J FISHER, I J REECE, A B HOUSTON, I HUTTON, D J WHEATLEY
Journal: Cardiovascular Research (1986)

Continuous wave Doppler ultrasound was used in vitro to assess the pressure differences across four different cardiac bioprosthetic valves in a pulsatile flow test apparatus. Valves were tested under four different flow conditions. Pressure differences were calculated from the maximum flow velocity measured by Doppler ultrasound and correlated well with the pressure differences measured directly in the flow model (r=0.98). Thus Doppler ultrasound can accurately measure pressure differences across bioprosthetic valves in vitro.
Atypical Protein Kinase Cι Is Required for Bronchioalveolar Stem Cell Expansion and Lung Tumorigenesis
Authors: Roderick P. Regala, Rebecca K. Davis, Alyssa Kunz, Andras Khoor, Michael Leitges, Alan P. Fields
Journal: Cancer Research (2009)

Abstract Protein kinase Cι (PKCι) is an oncogene required for maintenance of the transformed phenotype of non–small cell lung cancer cells. However, the role of PKCι in lung tumor development has not been investigated. To address this question, we established a mouse model in which oncogenic KrasG12D is activated by Cre-mediated recombination in the lung with or without simultaneous genetic loss of the mouse PKCι gene, Prkci. Genetic loss of Prkci dramatically inhibits Kras-initiated hyperplasia and subsequent lung tumor formation in vivo. This effect correlates with a defect in the ability of Prkci-deficient bronchioalveolar stem cells to undergo Kras-mediated expansion and morphologic transformation in vitro and in vivo. Furthermore, the small molecule PKCι inhibitor aurothiomalate inhibits Kras-mediated bronchioalveolar stem cell expansion and lung tumor growth in vivo. Thus, Prkci is required for oncogene-induced expansion and transformation of tumor-initiating lung stem cells. Furthermore, aurothiomalate is an effective antitumor agent that targets the tumor-initiating stem cell niche in vivo. These data have important implications for PKCι as a therapeutic target and for the clinical use of aurothiomalate for lung cancer treatment. [Cancer Res 2009;69(19):7603–11]
Method of assessing involved facial areas: rule of fours
Authors: H-S. Yoon, J-W. Choi, J-I. Youn
Journal: British Journal of Dermatology (2008)

Disease extent or affected area is probably the most easily and most frequently measured index of patient disability in dermatological disorders such as psoriasis. However, no standard method is available for assessing involved facial areas.To devise a method for assessing involved facial areas and to examine its validity and reliability.In study 1, the facial areas of 26 healthy adults were analysed and a new method for assessing facial areas was devised. In study 2, the validity and reliability of the devised method were investigated by 10 dermatologists using 30 photographs of patients with facial psoriasis.In study 1, facial regions were defined to have percentage areas that were multiples of 4% of the total facial area (which we refer to as the rule of fours), i.e. forehead 24%, one cheek 20%, perioral area 8%, one aspect of an ear 4%, one periorbital area 4%, and nose 4%. In study 2, a comparison of values obtained using the rule of fours with those obtained using an image analysis system showed excellent intrarater and inter-rater reliability when using the rule of fours.The rule of fours is useful for assessing involved facial areas. The application of this rule was found to provide an accurate and reliable method as compared with image analysis.
Assessment of Emotional Struggles in Type 2 Diabetes: Patient Perspectives
Authors: Elizabeth A. Beverly, Kelly M. Brooks, Marilyn D. Ritholz, Martin J. Abrahamson, Katie Weinger
Journal: Diabetes Care (2012)

Diabetic patients experience disproportionately high rates of depression, distress, and other psychosocial difficulties (1) that interfere with glycemia and self-care (2). Physicians recognize the frequency and seriousness of patients’ emotional struggles (3,4); however, many report that intervening is challenging because of limited treatment options, time constraints, and perceived lack of psychological expertise (4). Diabetes physicians may not feel comfortable or qualified to assess patients’ emotional difficulties because they have not received formal training in screening for these difficulties and do not have the resources/referral patterns necessary to provide patients with psychological support (4). Inquiring about patients’ preferences for addressing emotional struggles may help guide physicians in providing better support and treatment. As part of a larger qualitative study (4), we conducted in-depth interviews to explore patients’ perspectives about how their diabetes physicians approach emotional struggles during a medical visit.

We recruited participants aged 30–70 years who had been diagnosed with type 2 diabetes …
The clinical significance of bundle branch block complicating acute myocardial infarction. 1. Clinical characteristics, hospital mortality, and one-year follow-up.
Authors: M C Hindman, G S Wagner, M JaRo, J M Atkins, M M Scheinman, R W DeSanctis, A H Hutter, L Yeatman, M Rubenfire, C Pujura, M Rubin, J J Morris
Journal: Circulation (1978)

To provide an understanding of the clinical characteristics of patients with acute myocardial infarction (MI) and bundle branch block, experience from five centers was accumulated. Patients in whom bundle branch block first appeared after the onset of cardiogenic shock were excluded. In 432 patients, the most common types of block were left (38%) and right with left anterior fascicular block (34%). In 42% of the patients, bundle branch block was new. Progression to high degree (second or third degree) atrioventricular (AV) block via a Type II pattern occurred in 22% of the patients. Hospital and first year follow-up mortality rates were 28% and 28%, respectively. Only 46% of the patients developed pulmonary edema or shock (Killip Class III or IV), and hospital mortality was related to the amount of heart failure (8%, 7%, 27%, 83% for Killip Classes I-IV, respectively). Patients with progression to second degree or third degree AV block via a Type II pattern had increased hospital mortality compared with patients without this complication (47% vs 23%, P less than 0.001). In the absence of pulmonary edema or shock, patients with Type II second degree or third degree AV block still had a higher mortality rate than patients without advanced AV block (31% vs 2%, P less than 0.005), with nearly all the deaths due to abrupt development of AV block. Thus, in many patients MI with bundle branch block is associated with severe heart failure. However, this was not true for a majority of the patients, in whom therapy aimed at preventing morbidity and mortality due to the bradyarrhythmia of advanced AV block might be beneficial.