tbuckley/cabot-search huggingface dataset:
Distribution and Lysis of Weakly and Strongly Immunogenic Malignant Lymphoid Cells in Normal and Immune Mice: Effects of Prior Exposure to Heat or X-Irradiation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: John F. Nawrocki, Alfred T. Look, James F. Selwa, John R. Haggis, William H. Murphy
Journal: JNCI Journal of the National Cancer Institute (1984)

With the use of cells doubly labeled with 51Cr and 125I, an analysis was made of the distribution and lysis in normal and immune syngeneic C58 mice of weakly immunogenic malignant lymphocytes (Ib) and a highly immunogenic variant (IbN) derived from them. The results showed that 51Cr release was not a valid measure of tumor cell lysis in vivo. Prior exposure to 55 degrees C for 30 minutes caused Ib to lyse immediately after iv injection. Prior X-irradiation (10,000 R) enhanced the lysis of Ib in vivo but had only minor effects on IbN. In normal mice 125I-labeled Ib were entrapped in the lungs (approximately to 95%) immediately after iv injection, released in a diphasic manner, and then accumulated in the liver, spleen, bone marrow, and lymph nodes. In immune mice initial entrapment of Ib in the lungs was only about 42%, and label did not accumulate in the described organs. Heat-inactivated Ib were not retained to a significant degree in any of the organs of normal or immune mice. IbN were retained initially (2 hr) at values lower than Ib in the whole body, lungs, and livers of normal mice. 125I-labeled Ib were used to analyze how they were distributed and lysed in normal and immune mice during the first 6 hours after iv injection. To account for the loss of 125I from a tissue because of cell lysis (as distinct from cell redistribution), the amount of 125I associated with cells and blood plasma, and lost from the whole body, was quantified. A significant loss of 125I from the whole body began at 2 hours and continued at a linear rate thereafter. Non-cell-associated 125I occurred in the blood plasma at 1-2 hours and increased at a linear rate thereafter. These results made it possible to distinguish between loss of 125I from a tissue because of cell lysis as distinct from the redistribution of intact labeled cells.
Dual mechanisms by which miR-125b represses IRF4 to induce myeloid and B-cell leukemias
Authors: Alex Yick-Lun So, Reeshelle Sookram, Aadel A. Chaudhuri, Aarathi Minisandram, David Cheng, Catherine Xie, Ee Lyn Lim, Yvette Garcia Flores, Shuai Jiang, Jocelyn Tammy Kim, Christopher Keown, Parameswaran Ramakrishnan, David Baltimore
Journal: Blood (2014)
Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry
Authors: Timothy A Sanborn, Lynn A Sleeper, Eric R Bates, Alice K Jacobs, Jean Boland, John K French, Jo Dens, Vladimir Dzavik, Sebastian T Palmeri, John G Webb, Mark Goldberger, Judith S Hochman
Journal: Journal of the American College of Cardiology (2000)
Obstructive sleep apnoea: longer respiratory event lengths in patients with heart failure
Authors: Christina Efken, Thomas Bitter, Natalie Prib, Dieter Horstkotte, Olaf Oldenburg
Journal: European Respiratory Journal (2012)

This study investigated the effect of heart failure on respiratory patterns in patients with obstructive sleep apnoea (OSA). 39 patients with established OSA (apnoea/hypopnoea index (AHI) >10 events·h(-1)) and either with heart failure (New York Heart Association (NYHA) class II and III, left ventricular-ejection fraction (LVEF) ≤40%; n=26, age mean ± SD 67 ± 9 years) or without heart failure (LVEF ≥50%, N-terminal pro-brain naturic peptide <400 pg·mL(-1); n=13, age 73 ± 6 years) underwent simultaneous right- and left-heart catheterisation within 12 h of cardiorespiratory polygraphy recording. Respiratory patterns of OSA were significantly longer in OSA patients with heart failure versus without heart failure, including mean ± SD cycle length (46.0 ± 10.0 versus 37.8 ± 10.6 s; p=0.024), ventilation length (25.4 ± 6.3 versus 21.3 ± 7.1 s; p=0.044), apnoea length (20.5 ± 4.9 versus 16.5 ± 3.9 s; p=0.013), time-to-peak ventilation (10.6 ± 3.0 versus 8.3 ± 2.5 sc; p=0.021) and circulatory delay (28.5 ± 7.5 versus 22.6 ± 3.7 s; p=0.005). Positive and robust correlations were found between some of these parameters and the degree of congestion in heart failure: cycle length (r=0.53; p=0.006), ventilation length (r=0.55; p=0.004) and time-to-peak ventilation (r=0.47; p=0.015) all increased with a rise in pulmonary capillary wedge pressure. Respiratory patterns in OSA appear to be dependent on cardiac function, with an increase in event lengths as cardiac function decreases. In patients with heart failure, some of these events correlate with the degree of pulmonary congestion.
Profiles of Genomic Instability in High-Grade Serous Ovarian Cancer Predict Treatment Outcome
Authors: Zhigang C. Wang, Nicolai Juul Birkbak, Aedín C. Culhane, Ronny Drapkin, Aquila Fatima, Ruiyang Tian, Matthew Schwede, Kathryn Alsop, Kathryn E. Daniels, Huiying Piao, Joyce Liu, Dariush Etemadmoghadam, Alexander Miron, Helga B. Salvesen, Gillian Mitchell, Anna DeFazio, John Quackenbush, Ross S. Berkowitz, J. Dirk Iglehart, David D.L. Bowtell, Ursula A. Matulonis
Journal: Clinical Cancer Research (2012)

Abstract Purpose: High-grade serous cancer (HGSC) is the most common cancer of the ovary and is characterized by chromosomal instability. Defects in homologous recombination repair (HRR) are associated with genomic instability in HGSC, and are exploited by therapy targeting DNA repair. Defective HRR causes uniparental deletions and loss of heterozygosity (LOH). Our purpose is to profile LOH in HGSC and correlate our findings to clinical outcome, and compare HGSC and high-grade breast cancers. Experimental Design: We examined LOH and copy number changes using single nucleotide polymorphism array data from three HGSC cohorts and compared results to a cohort of high-grade breast cancers. The LOH profiles in HGSC were matched to chemotherapy resistance and progression-free survival (PFS). Results: LOH-based clustering divided HGSC into two clusters. The major group displayed extensive LOH and was further divided into two subgroups. The second group contained remarkably less LOH. BRCA1 promoter methylation was associated with the major group. LOH clusters were reproducible when validated in two independent HGSC datasets. LOH burden in the major cluster of HGSC was similar to triple-negative, and distinct from other high-grade breast cancers. Our analysis revealed an LOH cluster with lower treatment resistance and a significant correlation between LOH burden and PFS. Conclusions: Separating HGSC by LOH-based clustering produces remarkably stable subgroups in three different cohorts. Patients in the various LOH clusters differed with respect to chemotherapy resistance, and the extent of LOH correlated with PFS. LOH burden may indicate vulnerability to treatment targeting DNA repair, such as PARP1 inhibitors. Clin Cancer Res; 18(20); 5806–15. ©2012 AACR.
Microcirculation. The third force
Authors: G. De Takats
Journal: JAMA (1966)

Microcirculation, "the third force" in the cardiovascular circuit, has been ignored for many years, while spectacular advances have taken place in cardiovascular surgery. Still, if microcirculation fails, tissue nutrition is impaired and cardiovascular repair becomes futile. <h3>Functional Pathology.—</h3> Microcirculation is the function of the terminal vascular bed, the vessels having a diameter of 100μ or less. It is by no means a homogeneous apparatus, since it consists of a number of segments which do not react simultaneously or even in the same direction (Fig 1). Teleologically speaking,<sup>*</sup>the stabilization of capillary pressure is one of its main objects; adequate tissue nutrition is thus maintained. This is accomplished by autcregulation, by which one implies that there is<i>an intrinsic tendency of an organ to maintain constant blood flow, despite changes in arterial perfusion pressure</i>.<sup>1</sup>It is a mechanism for maintaining nutrient flow when arterial pressure is reduced locally or systematically,
Measurement and correlation of wedged hepatic, intrahepatic, intrasplenic and intravariceal pressures in patients with cirrhosis of liver and non-cirrhotic portal fibrosis.
Authors: S K Sarin, K K Sethi, R Nanda
Journal: Gut (1987)

In order to examine the relationship of various haemodynamic parameters in two different liver diseases, 10 patients with cirrhosis of liver and 14 patients with non-cirrhotic portal fibrosis were studied. In cirrhotics, mean (+/- SD) wedged hepatic (25.8 +/- 6.4 mmHg), intrahepatic (24.5 +/- 6.2 mmHg) and intrasplenic (25.0 +/- 5.6 mmHg) pressures correlated significantly (p less than 0.001) with intravariceal (25.2 +/- 6.7) pressure measurements. In patients with NCPF, mean (+/- SD) wedged hepatic (9.1 +/- 3.7 mmHg) and intraphepatic (15.4 +/- 5.8 mmHg) pressures were significantly (p less than 0.01) lower than the intrasplenic (24.5 +/- 4.2 mmHg) and intravariceal (23.96 +/- 5.6 mmHg) pressures. Two independent pressure gradients, one between intrasplenic and intrahepatic pressure (8.9 +/- 6.5 mmHg) and another between intrahepatic and wedged hepatic venous pressure (6.2 +/- 5.6 mmHg) were seen in non-cirrhotic portal fibrosis patients, indicating the likelihood of both pre- and perisinusoidal resistance to flow of portal venous blood in these patients. A highly significant (p less than 0.001) correlation between intravariceal and intrasplenic pressures was found in patients with cirrhosis of liver (r = 0.93), as well as in patients with non-cirrhotic portal fibrosis (r = 0.85). No correlation was found between the size of oesophageal varices and wedged hepatic and intrahepatic pressures. Patients with grade 4 varices had significantly higher intravariceal (p less than 0.01) and intrasplenic (p less than 0.05) pressure than patients with grade 2 varices. It can be concluded that intravariceal pressure is representative of portal pressure in patients with cirrhosis of liver as well as in non-cirrhotic portal fibrosis patients and it can be recommended as the single haemodynamic investigation in patients with portal hypertension and oesophageal varices.
Pulmonary Capillary Wedge Pressure Augments Right Ventricular Pulsatile Loading
Authors: Ryan J. Tedford, Paul M. Hassoun, Stephen C. Mathai, Reda E. Girgis, Stuart D. Russell, David R. Thiemann, Oscar H. Cingolani, James O. Mudd, Barry A. Borlaug, Margaret M. Redfield, David J. Lederer, David A. Kass
Journal: Circulation (2011)

Background— Right ventricular failure from increased pulmonary vascular loading is a major cause of morbidity and mortality, yet its modulation by disease remains poorly understood. We tested the hypotheses that, unlike the systemic circulation, pulmonary vascular resistance (R PA ) and compliance (C PA ) are consistently and inversely related regardless of age, pulmonary hypertension, or interstitial fibrosis and that this relation may be changed by elevated pulmonary capillary wedge pressure, augmenting right ventricular pulsatile load. Methods and Results— Several large clinical databases with right heart/pulmonary catheterization data were analyzed to determine the R PA -C PA relationship with pulmonary hypertension, pulmonary fibrosis, patient age, and varying pulmonary capillary wedge pressure. Patients with suspected or documented pulmonary hypertension (n=1009) and normal pulmonary capillary wedge pressure displayed a consistent R PA -C PA hyperbolic (inverse) dependence, C PA =0.564/(0.047+R PA ), with a near-constant resistance-compliance product (0.48±0.17 seconds). In the same patients, the systemic resistance-compliance product was highly variable. Severe pulmonary fibrosis (n=89) did not change the R PA -C PA relation. Increasing patient age led to a very small but statistically significant change in the relation. However, elevation of the pulmonary capillary wedge pressure (n=8142) had a larger impact, significantly lowering C PA for any R PA and negatively correlating with the resistance-compliance product ( P &lt;0.0001). Conclusions— Pulmonary hypertension and pulmonary fibrosis do not significantly change the hyperbolic dependence between R PA and C PA , and patient age has only minimal effects. This fixed relationship helps explain the difficulty of reducing total right ventricular afterload by therapies that have a modest impact on mean R PA . Higher pulmonary capillary wedge pressure appears to enhance net right ventricular afterload by elevating pulsatile, relative to resistive, load and may contribute to right ventricular dysfunction.
Alternative Medicine: A “Mirror Image” for Scientific Reasoning in Conventional Medicine
Authors: Jan P. Vandenbroucke, Anton J.M. de Craen
Journal: Annals of Internal Medicine (2001)

A reflection on the scientific behavior of adherents of conventional medicine toward one form of alternative medicine—homeopathy—teaches us that physicians do reject seemingly solid evidence because it is not compatible with theory. Further reflection, however, shows that physicians do the same within conventional medical science: Sometimes they discard a theory because of new facts, but at other times they cling to a theory despite the facts. This essay highlights the seeming contradiction and discusses whether it still permits the building of rational medical science. We propose that rational science is compatible with physicians' behavior, provided that physicians acknowledge the subjective element in the evaluation of science, as exemplified in the crossword analogy by the philosopher Haack. This type of thinking fits very well with the Bayesian approach to decision making that has been advocated for decades in clinical medicine. It does not lead to complete and uncontrollable subjectivity because discernment between rivaling explanations is still possible through argument and counterargument.
P107 Effectiveness of omalizumab on asthma control and lung function in severe allergic asthma patients in the Czech Republic
Authors: V. Sedlak
Journal: Thorax (2011)

<h3>Introduction</h3> Anti-IgE therapy (omalizumab) is indicated for severe persistent allergic asthma, which is uncontrolled despite appropriate therapy according to current GINA guidelines. <h3>Aim of this study</h3> Aim of this study was to describe changes of selected parameters (FEV<sub>1</sub>, life quality and FeNO<sub>50</sub>) in all patients treated with omalizumab in the Czech Republic for more than 12 months in a real life clinical setting. <h3>Methods</h3> Data of 127 patients treated 12 months by omalizumab in eight Czech centres were prospectively observed in Czech Anti-IgE Registry and analysed. Respiratory specialist and allergist together decided indication of anti-IgE therapy after extensive evaluation process in each patient. <h3>Results</h3> Median IgE level was 223 IU/ml, all patients experienced during previous year at least two exacerbation treated by oral steroid burst. 69 patients were dependent on oral steroids, mean dose 5 mg prednisolone/day. After 12 months of omalizumab therapy FEV<sub>1</sub> improved from 65% to 72% (p&lt;0.001), asthma control test changed from 13 to 18 points score (p&lt;0.001) and FeNO<sub>50</sub> decreased from 48 to 32 ppb (p=0.001). Emergency visits, steroid bursts for asthma exacerbation and mean oral steroid dose were lower after the 12 months of therapy as well (all p&lt;0.001). Observed side effects were mild (headache, weight gain) in 21.3% patients. Overall response to anti-IgE therapy measured by clinical evaluation of treatment benefit was 80.8%. <h3>Conclusion</h3> Rigorous selection of candidates for anti-IgE therapy based on consensus of allergology and respiratory specialists leads to very good therapeutic response, we have observed significant improvement in lung functions.
Brain Plasticity Through the Life Span: Learning to Learn and Action Video Games
Authors: Daphne Bavelier, C. Shawn Green, Alexandre Pouget, Paul Schrater
Journal: Annual Review of Neuroscience (2012)

The ability of the human brain to learn is exceptional. Yet, learning is typically quite specific to the exact task used during training, a limiting factor for practical applications such as rehabilitation, workforce training, or education. The possibility of identifying training regimens that have a broad enough impact to transfer to a variety of tasks is thus highly appealing. This work reviews how complex training environments such as action video game play may actually foster brain plasticity and learning. This enhanced learning capacity, termed learning to learn, is considered in light of its computational requirements and putative neural mechanisms.
Differential Effects of Rapamycin in Anti-GBM Glomerulonephritis
Authors: Kathrin Hochegger, Gerhard L. Jansky, Afschin Soleiman, Anna M. Wolf, Andrea Tagwerker, Christoph Seger, Andrea Griesmacher, Gert Mayer, Alexander R. Rosenkranz
Journal: Journal of the American Society of Nephrology (2008)

The immunosuppressive mammalian target of rapamycin inhibitor rapamycin is widely used in solid-organ transplantation, but the effect of rapamycin on kidney disease is controversial. This study evaluated the effect of rapamycin in the autologous phase of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. Disease was induced by preimmunizing the animals with rabbit IgG 5 d before administration of rabbit anti-mouse GBM antiserum. When rapamycin was started on the day of immunization (group 1), mice were protected from glomerulonephritis, suggested by a dramatic decrease in albuminuria, influx of inflammatory cells, and Th1-cytokine expression in the kidneys. Activation of T cells and production of autologous mouse anti-rabbit IgG were also significantly reduced in rapamycin-treated animals. In contrast, when rapamycin was started 14 d after immunization (group 2), mice had a significant increase in albuminuria and renal infiltration of inflammatory cells compared with vehicle-treated animals, and there were no differences in T and B cell responses. A significant decrease in vascular endothelial growth factor-A and an increase in IL-6 were detected in kidneys of these rapamycin-treated mice. In conclusion, rapamycin has the potential to significantly reduce the B and T cell responses and thereby protect from glomerulonephritis when administered early in disease. Once disease is established, however, rapamycin seems to worsen glomerulonephritis by disturbing the endothelial cell/vascular endothelial growth factor system in the kidney.
N<scp>EW</scp> I<scp>NSIGHTS INTO THE</scp> D<scp>IVERSITY AND</scp> F<scp>UNCTION OF</scp> N<scp>EURONAL</scp> I<scp>MMUNOGLOBULIN</scp> S<scp>UPERFAMILY</scp> M<scp>OLECULES</scp>
Authors: Geneviève Rougon, Oliver Hobert
Journal: Annual Review of Neuroscience (2003)

Immunoglobulin superfamily (IgSF) proteins are implicated in diverse steps of brain development, including neuronal migration, axon pathfinding, target recognition and synapse formation, as well as in the maintenance and function of neuronal networks in the adult. We provide here a review of recent findings on the diversity and the role of transmembrane and secreted members of IgSF proteins in the nervous system. We illustrate that the complexity of IgSF protein function results from various different levels of regulation including regulation of gene expression, protein localization, and protein interactions.
Can the measurement of amylase in drain after distal pancreatectomy predict post-operative pancreatic fistula?
Authors: Roberto Cirocchi, Luigina Graziosi, Alessandro Sanguinetti, Carlo Boselli, Andrea Polistena, Claudio Renzi, Jacopo Desiderio, Giuseppe Noya, Amilcare Parisi, Masahiko Hirota, Annibale Donini, Nicola Avenia
Journal: International Journal of Surgery (2015)
Physiological performance of patients with COPD during activities of daily living after a physical training with and without inspiratory muscle training: Preliminary results
Authors: Eloisa Regueiro, Renata Basso, Saulo Fabrin, Caroline Martins, Mauricio Jamami, Dirceu Costa, Thierry Troosters, Valéria Pires Di Lorenzo
Journal: European Respiratory Journal (2012)

Background : Physical training (PT) improves performance of activities of daily living (ADL), decreases dyspnea and enhances the inspiratory muscle strength in patients with COPD. Less is known on the physiological benefits during the execution of ADL in patients treated with general PT (GPT) or GPT plus inspiratory muscle training (IMT).   Aim : To compare changes on ventilatory and metabolic responses, dyspnea, SpO 2  and time during a set of ADL after two PT programs.   Methods : A set of 5 ADL (making bed (1), taking shower (2), brushing teeth (3), lifting and lowering containers above eye level (4) and below the pelvic waist (5) was performed by 28 patients before and after a 16 week: 13 GPT (aerobic training) (FEV 1 43±4%pred, 67±2yrs) and 15 GPT+IMT with PowerBreathe (FEV 1 51±3%pred, 67±3yrs). A metabolic system was used during ADL.   Results : Both groups had significant reduction (p 2 , Borg,  SpO2  and time in ADL within them, although there are no difference between GPT and GPT+IMT throughout the performance of ADL (Table1).   Conclusion : These results suggest that both groups improved their performance in the ADL. Adding IMT did not show additional benefits on physiological variables on performance of ADL.
Prediction of recovery of myocardial dysfunction after revascularization comparison of fluorine-18 fluorodeoxyglucose/thallium-201 SPECT, thallium-201 stress-reinjection SPECT and dobutamine echocardiography
Authors: Jeroen J. Bax, Jan H. Cornel, Frans C. Visser, Paolo M. Fioretti, Arthur van Lingen, Ambroos E.M. Reijs, Eric Boersma, Gerrit J.J. Teule, Cees A. Visser
Journal: Journal of the American College of Cardiology (1996)
Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1-Related Breast Cancer
Authors: Ashish Juvekar, Laura N. Burga, Hai Hu, Elaine P. Lunsford, Yasir H. Ibrahim, Judith Balmañà, Anbazhagan Rajendran, Antonella Papa, Katherine Spencer, Costas A. Lyssiotis, Caterina Nardella, Pier Paolo Pandolfi, José Baselga, Ralph Scully, John M. Asara, Lewis C. Cantley, Gerburg M. Wulf
Journal: Cancer Discovery (2012)

There is a need to improve treatments for metastatic breast cancer. Here, we show the activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in a MMTV-CreBrca1(f/f)Trp53(+/-) mouse model of breast cancer. When treated with the pan-class IA PI3K inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days. NVP-BKM120 reduced AKT phosphorylation, tumor cell proliferation, and angiogenesis. Resistant tumors maintained suppression of AKT phosphorylation but exhibited activation of the MAPK pathway at the "pushing margin." Surprisingly, PI3K inhibition increased indicators of DNA damage, poly-ADP-ribosylation (PAR), and γ-H2AX, but decreased Rad51 focus formation, suggesting a critical role of PI3K activity for Rad51 recruitment. The PARP inhibitor olaparib alone attenuated tumor growth modestly; however, the combination of NVP-BKM120 and olaparib delayed tumor doubling to more than 70 days in the mouse model and more than 50 days in xenotransplants from human BRCA1-related tumors, suggesting that combined PI3K and PARP inhibition might be an effective treatment of BRCA1-related tumors.Current treatment options for triple-negative breast cancer are limited to chemotherapeutic regimens that have considerable toxicity and are not curative. We report here that the combination of a PI3K inhibitor with a PARP inhibitor provides in vivo synergy for treatment of an endogenous mouse model for BRCA1-related breast cancers, making this a candidate combination to be tested in human clinical trials.