tbuckley/cabot-search huggingface dataset:
Cancer Patient Preferences for Communication of Prognosis in the Metastatic Setting
Authors: Rebecca G. Hagerty, Phyllis N. Butow, Peter A. Ellis, Elizabeth A. Lobb, Susan Pendlebury, Natasha Leighl, David Goldstein, Sing Kai Lo, Martin H.N. Tattersall
Journal: Journal of Clinical Oncology (2004)

Purpose To identify preferences for and predictors of prognostic information among patients with incurable metastatic cancer. Patients and Methods One hundred twenty-six metastatic cancer patients seeing 30 oncologists at 12 outpatient clinics in New South Wales, Australia, participated in the study. Patients were diagnosed with incurable metastatic disease within 6 weeks to 6 months of recruitment. Patients completed a survey eliciting their preferences for prognostic information, including type, quantity, mode, and timing of presentation; anxiety and depression levels; and information and involvement preferences. Results More than 95% of patients wanted information about side effects, symptoms, and treatment options. The majority wanted to know longest survival time with treatment (85%), 5-year survival rates (80%), and average survival (81%). Words and numbers were preferred over pie charts or graphs. Fifty-nine percent (59%) wanted to discuss expected survival when first diagnosed with metastatic disease. Thirty-eight percent and 44% wanted to negotiate when expected survival and dying, respectively, were discussed. Patients with higher depression scores were more likely to want to know shortest time to live without treatment (P = .047) and average survival (P = .049). Lower depression levels were significantly associated with never wanting to discuss expected survival (P = .03). Patients with an expected survival of years were more likely to want to discuss life expectancy when first diagnosed with metastases (P = .02). Conclusion Most metastatic cancer patients want detailed prognostic information but prefer to negotiate the extent, format, and timing of the information they receive from their oncologists.
Comparison of two training programmes in chronic airway limitation patients: standardized versus individualized protocols
Authors: G Vallet, S Ahmaidi, I Serres, C Fabre, D Bourgouin, J Desplan, A Varray, C Prefaut
Journal: European Respiratory Journal (1997)

This study tested the effect of two methods of training, one individualized at the heart rate corresponding to the gas exchange threshold (GET) and the other at the heart rate corresponding to 50% of maximal heart rate reserve, on maximal and submaximal cardiorespiratory response in 24 patients with chronic airway limitation (CAL). The patients were randomly assigned to either the individualized training group (IT; n = 12) or the standardized training group (ST; n = 12). The training programme consisted of 4 weeks of stationary bicycle exercise, 5 days.week-1. Before reconditioning began, the target level based on heart rate was not significantly different between groups (109 +/- 4 versus 110 +/- 3 beats.min-1, in IT and ST, respectively). Post-training, a significant increase in symptom-limited oxygen uptake (V'O2.sl) and maximal O2 pulse was found in IT, whereas ST exhibited no significant change. In each group, GET was statistically increased in much the same way as V'O2,sl, with a higher increase in IT (p &lt; 0.01) than ST (p &lt; 0.05). Nevertheless, IT exhibited a concomitant and gradual decrease in minute ventilation (V'E), carbon dioxide production (V'CO2), and venous lactate concentration ([La]), whereas ST presented no significant change in these parameters (intergroup p &lt; 0.01). Breathing pattern was also altered after IT, at the same metabolic level and at the same ventilation level (intergroup p &lt; 0.05). Cardiac responses were modified in the two groups. At the same metabolic level, a significantly lower cardiac frequency was found both for IT and ST (intragroup p &lt; 0.05 after training). In contrast, the increase in O2 pulse was only significantly higher in It after training. These data show the greater efficiency of an individualized training protocol based on determination of gas exchange threshold as compared to a standardized protocol, in improving exercise performance, when applied to a patient group. Despite an apparently similar target training level, the individualized method clearly optimized the physiological training effects in patients with chronic airway limitation and, more particularly, decreased their ventilatory requirement.
ANTIBODY RESPONSE OF INBRED MOUSE STRAINS TO ORDERED TETRAPEPTIDES OF TYROSINE AND GLUTAMIC ACID ATTACHED TO MULTICHAIN POLYALANINE OR POLYPROLINE
Authors: Edna Mozes, Michal Schwartz, Michael Sela
Journal: The Journal of Experimental Medicine (1974)

Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.
Involvement of Vacuolar H+-Adenosine Triphosphatase Activity in Multidrug Resistance in HL60 Cells
Authors: D. Marquardt, M. S. Center
Journal: JNCI Journal of the National Cancer Institute (1991)

HL60 cells isolated for resistance to vincristine (HL60/Vinc cells) or doxorubicin (HL60/Adr cells) contain enhanced levels of and energy-dependent drug efflux pump. HL60/Vinc cells contain the drug transporter P-glycoprotein, whereas the HL60/Adrisolate does not In the present study, we examined the possible involvement of vacuolar H + -adenosine triphos-phatase (H + -ATPase) activity in drug resistance in HL60 cells. We utilized bafilomycin A 19 , and agent which selectively inhibits vacuolar H + -ATPase activity at low concentrations. The results showed that bafilomycin A 1 induced a major increase in drug accumulation and inhibited drug efflux in both HL60/Adr cells and HL60/Vinc cells. Similar results were obtained with 7-chloro-4–nitrobenz–2–oxa 1, 3 diazole, and agent which is also capable of inhibiting vacuolar H + -ATPase. Azide, an inhibitor of F 1 F 0 mitochondrial ATPase, and vanadate and ouabain, which are inhibitors of E 1 E 2 -type ATPase, did not affect drug levels in resistant cells. We also observed that bafilomycin A 1 did not compete with ( 3 H)azidopine binding to P-glycoprotein. Thus, bafilomycin A 1 does not appear to function as a substrate for P-glycoprotein. These results suggest an involvement of vacuolar H + -ATPase activity in the pathway of drug efflux from HL60/Adr cells and HL60/brief-report Vinc cells. The mechanism of this action remains to be determined. [J Natl Cancer Inst 83: 1098–1102, 1991]
Eosinophils versus Neutrophils in Host Defense
Authors: David A. Bass, Pamela Szejda
Journal: Journal of Clinical Investigation (1979)

Eosinophil leukocytes have been reported to have a major role in host defense against invasive, migratory phases of helminth infestations, yet the relative larvicidal abilities of eosinophils and neutrophils have not been thoroughly examined. This study examined the killing of newborn (migratory phase) larvae of Trichinella spiralis during incubation by human granulocytes in vitro. The assay employed cultue of larvae with cells, sera, and reagents in microtiter wells with direct counting of surviving larvae after incubation. Killed larvae appeared to be lysed. Verification of the microplate assay was obtained by demonstrating complete loss of infectivity of larvae incubated with leukocytes and immune serum. In the presence of optimal immune serum concentrations, purified neutrophils or eosinophils achieved >/=95% killing of larvae at cell:larva ratios of 2,000:1 or greater. Fresh normal serum prompted slight (19%) killing by leukocytes at a cell:larva ratio of 9,000:1. Cells plus heat-inactivated normal serum and all sera preparations in the absence of leukocytes killed <8% of the larvae. The activity of immune serum was opsonic. Cells adhered to larvae that had been preincubated in immune serum, and immunofluorescent studies indicated that such preopsonized larvae were coated with immunoglobulin (Ig)G. However, preopsonized larvae lost opsonic activity and surface IgG during incubation for 3 h in medium lacking immune serum. The rate of killing was dependent on the cell:larva ratio; at high leukocyte concentrations (4,200:1), 99% were killed within 7 h; at lower cell:larva ratios, killing increased steadily during a 20-h incubation period. Killing was inhibited by 20 mug catalase, 5 mug/ml cytochalasin B, or 5muM colchicine, but was unchanged by superoxide dismutase and was enhanced by azide or cyanide. Leukocytes from a patient with chronic granulomatous disease, lacking ability to mount a normal oxidative response, demonstrated a markedly suppressed larvicidal effect. The data indicate that neutrophils are at least as effective as eosinophils in the killing of newborn larvae of T. spiralis. The killing appeared to be mediated by the oxidative metabolic burst with its generation of hydrogen peroxide.
APPLICATIONS OF MASS ISOTOPOMER ANALYSISTO NUTRITION RESEARCH
Authors: Henri Brunengraber, Joanne K. Kelleher, Christine Des Rosiers
Journal: Annual Review of Nutrition (1997)

▪ Abstract Investigations into regulating metabolic pathways with stable isotopes have, over the past decade, undergone major development with the use of nuclear magnetic resonance and mass spectrometry in studying labeling patterns of newly synthesized biomolecules. In this review, we concentrate on investigations of mass isotopomer distribution (MID) measured by mass spectrometry. We review the applications of MID to analytical problems, in particular the possibility of amplifying the measurement of low isotopic enrichments by incorporating multiple molecules or atoms of a primary analyte into the molecule of a secondary analyte, the MID of which is assayed. We also review new information on the regulation of intermediary metabolism gathered from the analysis of MID patterns of synthesized compounds. Lastly, we review the applications of MID to the synthesis of polymeric molecules, with emphasis on the validity of these techniques. A number of these techniques are applicable to investigations of nutrient metabolism in health and disease.
Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease
Authors: M P Conte, S Schippa, I Zamboni, M Penta, F Chiarini, L Seganti, J Osborn, P Falconieri, O Borrelli, S Cucchiara
Journal: Gut (2006)

Clinical and experimental observations in animal models indicate that intestinal commensal bacteria are involved in the initiation and amplification of inflammatory bowel disease (IBD). No paediatric reports are available on intestinal endogenous microflora in IBD.To investigate and characterise the predominant composition of the mucosa-associated intestinal microflora in colonoscopic biopsy specimens of paediatric patients with newly diagnosed IBD.Mucosa-associated bacteria were quantified and isolated from biopsy specimens of the ileum, caecum and rectum obtained at colonoscopy in 12 patients with Crohn's disease, 7 with ulcerative colitis, 6 with indeterminate colitis, 10 with lymphonodular hyperplasia of the distal ileum and in 7 controls. Isolation and characterisation were carried out by conventional culture techniques for aerobic and facultative-anaerobic microorganisms, and molecular analysis (16S rRNA-based amplification and real-time polymerase chain reaction assays) for the detection of anaerobic bacterial groups or species.A higher number of mucosa-associated aerobic and facultative-anaerobic bacteria were found in biopsy specimens of children with IBD than in controls. An overall decrease in some bacterial species or groups belonging to the normal anaerobic intestinal flora was suggested by molecular approaches; in particular, occurrence of Bacteroides vulgatus was low in Crohn's disease, ulcerative colitis and indeterminate colitis specimens.This is the first paediatric report investigating the intestinal mucosa-associated microflora in patients of the IBD spectrum. These results, although limited by the sample size, allow a better understanding of changes in mucosa-associated bacterial flora in these patients, showing either a predominance of some potentially harmful bacterial groups or a decrease in beneficial bacterial species. These data underline the central role of mucosa-adherent bacteria in IBD.
Retinal Vascular Geometry Predicts Incident Retinopathy in Young People With Type 1 Diabetes
Authors: Paul Benitez-Aguirre, Maria E. Craig, Muhammad Bayu Sasongko, Alicia J. Jenkins, Tien Yin Wong, Jie Jin Wang, Ning Cheung, Kim C. Donaghue
Journal: Diabetes Care (2011)

To examine the association between retinal vascular geometry and subsequent development of incident retinopathy in young patients with type 1 diabetes.A prospective cohort study of 736 people with type 1 diabetes aged 12 to 20 years, retinopathy-free at baseline, attending an Australian tertiary care hospital. Retinopathy was determined from seven-field retinal photographs according to the modified Airlie House Classification. Retinal vascular geometry, including length/diameter ratio (LDR) and simple tortuosity (ST), was quantified in baseline retinal photographs. Generalized estimating equations were used to determine risk of retinopathy associated with baseline LDR and ST, adjusting for other factors.After a median 3.8 (interquartile range 2.4-6.1) years of follow-up, incident retinopathy developed in 287 of 736 (39%). In multivariate analysis, lower arteriolar LDR (odds ratio 1.8 [95% CI 1.2-2.6]; 1st vs. 4th quartile) and greater arteriolar ST (1.5 [1.0-2.2]; 4th vs. 1st quartile) predicted incident retinopathy after adjusting for diabetes duration, sex, A1C, blood pressure, total cholesterol, and BMI. In subgroup analysis by sex, LDR predicted incident retinopathy in male and female participants (2.1 [1.1-4.0] and 1.7 [1.1-2.7]; 1st vs. 4th quartiles, respectively) and greater arteriolar ST predicted incident retinopathy in male participants (2.4 [1.1-4.4]; 4th vs. 1st quartile) only.Lower arteriolar LDR and greater ST were independently associated with incident retinopathy in young people with type 1 diabetes. These vascular geometry measures may serve as risk markers for diabetic retinopathy and provide insights into the early structural changes in diabetic microvascular complications.
Prasugrel Compared With High Loading- and Maintenance-Dose Clopidogrel in Patients With Planned Percutaneous Coronary Intervention
Authors: Stephen D. Wiviott, Dietmar Trenk, Andrew L. Frelinger, Michelle O’Donoghue, Franz-Josef Neumann, Alan D. Michelson, Dominick J. Angiolillo, Hanoch Hod, Gilles Montalescot, Debra L. Miller, Joseph A. Jakubowski, Richard Cairns, Sabina A. Murphy, Carolyn H. McCabe, Elliott M. Antman, Eugene Braunwald
Journal: Circulation (2007)

Background— The increasing use of higher-than-approved doses of clopidogrel in clinical practice is based in part on the desire for greater levels of inhibition of platelet aggregation (IPA). Prasugrel is a new thienopyridine that is more potent than standard-dose clopidogrel in healthy subjects and patients with stable coronary artery disease. The relative antiplatelet effects of prasugrel versus high-dose clopidogrel in percutaneous coronary intervention patients are unknown. Methods and Results— Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation–Thrombolysis in Myocardial Infarction 44 (PRINCIPLE-TIMI 44) was a randomized, double-blind, 2-phase crossover study of prasugrel compared with high-dose clopidogrel in patients undergoing cardiac catheterization for planned percutaneous coronary intervention. The primary end point of the loading-dose phase (prasugrel 60 mg versus clopidogrel 600 mg) was IPA with 20 μmol/L ADP at 6 hours. Patients with percutaneous coronary intervention entered the maintenance-dose phase, a 28-day crossover comparison of prasugrel 10 mg/d versus clopidogrel 150 mg/d with a primary end point of IPA after 14 days of either drug. In this study, 201 subjects were randomized. IPA at 6 hours was significantly higher in subjects receiving prasugrel (mean±SD, 74.8±13.0%) compared with clopidogrel (31.8±21.1%; P &lt;0.0001). During the maintenance-dose phase, IPA with 20 μmol/L ADP was higher in subjects receiving prasugrel (61.3±17.8%) compared with clopidogrel (46.1±21.3%; P &lt;0.0001). Results were consistent across all key secondary end points; significant differences emerged by 30 minutes and persisted across all time points. Conclusions— Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.
Mutational Studies on Resurrected Ancestral Proteins Reveal Conservation of Site-Specific Amino Acid Preferences throughout Evolutionary History
Authors: Valeria A. Risso, Fadia Manssour-Triedo, Asunción Delgado-Delgado, Rocio Arco, Alicia Barroso-delJesus, Alvaro Ingles-Prieto, Raquel Godoy-Ruiz, Jose A. Gavira, Eric A. Gaucher, Beatriz Ibarra-Molero, Jose M. Sanchez-Ruiz
Journal: Molecular Biology and Evolution (2014)

Local protein interactions ("molecular context" effects) dictate amino acid replacements and can be described in terms of site-specific, energetic preferences for any different amino acid. It has been recently debated whether these preferences remain approximately constant during evolution or whether, due to coevolution of sites, they change strongly. Such research highlights an unresolved and fundamental issue with far-reaching implications for phylogenetic analysis and molecular evolution modeling. Here, we take advantage of the recent availability of phenotypically supported laboratory resurrections of Precambrian thioredoxins and β-lactamases to experimentally address the change of site-specific amino acid preferences over long geological timescales. Extensive mutational analyses support the notion that evolutionary adjustment to a new amino acid may occur, but to a large extent this is insufficient to erase the primitive preference for amino acid replacements. Generally, site-specific amino acid preferences appear to remain conserved throughout evolutionary history despite local sequence divergence. We show such preference conservation to be readily understandable in molecular terms and we provide crystallographic evidence for an intriguing structural-switch mechanism: Energetic preference for an ancestral amino acid in a modern protein can be linked to reorganization upon mutation to the ancestral local structure around the mutated site. Finally, we point out that site-specific preference conservation naturally leads to one plausible evolutionary explanation for the existence of intragenic global suppressor mutations.
Foxp3 expression in breast cancer patient from Qatar: survival analysis
Authors: Mahmoud G Mohamed, Hina Sarwath, Shaykha Alqahtani, Salha Bujjasoum, Imad Mujeeb, Mufeed Almesteri, Hikmat Bugrein, Prem Chandra, Shahinaz Bedri
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts In breast cancer, the presence of Foxp3 (Tregs) [[1][1]] within the tumor milieu has been a matter of debate. Some studies have determined that infiltration of Tregs was associated with poor survival, while others revealed no impact on survival, however this depends on their type
Virological diagnosis in community-acquired pneumonia in immunocompromised patients
Authors: M. Camps Serra, C. Cervera, T. Pumarola, A. Moreno, R. Perelló, A. Torres, M. T. Jiménez de Anta, M. A. Marcos
Journal: European Respiratory Journal (2007)

Community-acquired pneumonia (CAP) is a serious lower respiratory tract infection associated with significant morbidity and mortality in immunocompromised patients. The present study evaluated the clinical spectrum of CAP in immunocompromised hosts and the role of respiratory viruses, as well as the yield of viral diagnostic methods. Conventional microbiological tests were routinely performed in immunocompromised patients with CAP. Nasopharyngeal swabs were processed for respiratory viruses by indirect immunofluorescence assay, cell culture and PCR. Four groups were defined according to aetiology of CAP, as follows: group 1 (nonviral), group 2 (mixed, nonviral and viral), group 3 (only viral) and group 4 (unknown aetiology). Over a 1-yr period, 92 patients were included. An aetiological diagnosis was achieved in 61 (66%) patients: 38 (41%), group 1; 12 (13%), group 2; and 11 (12%), group 3. The most frequent pathogen detected was Streptococcus pneumoniae (n = 29, 48%), followed by rhinovirus (n = 11, 18%). PCR identified 95% of respiratory viruses. Clinical characteristics could not reliably distinguish among the different aetiological groups. Respiratory viruses represent a substantial part of the aetiologies of community-acquired pneumonia in immunocompromised patients and its routine assessment through PCR in nasopharyngeal swabs should be considered in the clinical care of these patients.
Abstract 9945: Concomitant Early Repolarization Increases Occurrences of Ventricular Fibrillation in Patients with Acute Myocardial Infarctions
Authors: Yoshihisa Naruse, Hiroshi Tada, Yoshie Harimura, Mayu Hayashi, Noriyuki Takeyasu, Akira Sato, Yukio Sekiguchi, Kentaro Yoshida, Kazutaka Aonuma
Journal: Circulation (2011)

Background: Previous studies demonstrated that there is an increased prevalence of electrocardiographic early repolarization among patients with a history of idiopathic ventricular fibrillation (VF). Early repolarization is also associated with life threatening ventricular tachyarrhythmias in patients with chronic coronary artery disease. However, no studies have clarified whether or not there is an association between electrocardiographic early repolarization and the VF occurrences after the onset of acute myocardial infarction (AMI). Methods: This study included 220 consecutive patients with AMIs (69±11 years; 57 females) in whom 12-lead ECGs before the AMI onset could be evaluated. The patients were classified based on the VF occurrence within 48 hours after the AMI onset. Sustained VF was defined as that lasting longer than 30 seconds or that required electrical cardioversion. Early repolarization was electrocardiographically defined as an elevation of the QRS-ST junction of &gt;0.1 mV from baseline in at least 2 inferior or lateral leads, manifested as QRS slurring or notching. Results: Twenty-one (10%) patients experienced an episode of VF within 48 hours of AMI onset. Compared to the patients without VF, the VF patients had a higher prevalence of early repolarization (p&lt;0.001) and male gender (p&lt;0.05), a shorter duration from onset to admission (p&lt;0.05), and a greater number of diseased coronary arteries (p&lt;0.05) and Killip class (p&lt;0.001). A multivariate analysis revealed that early repolarization (odds ratio [OR]=6.45; 95% confidence interval [CI]= 2.07-20.40; p&lt;0.01), a time from onset to admission less than 180 minutes (OR=3.54; 95% CI=1.08-11.53; p&lt;0.05), and a Killip class greater than I (OR=11.43; 95% CI=3.22-40.59; p&lt;0.001) were independent predictors of VF occurrences. Conclusion: The presence of early repolarization increases the risk of VF occurrences within 48 hours after the AMI onset.