tbuckley/cabot-search huggingface dataset:
Disease gravity and urgency of need as guidelines for liver allocation
Authors: Bijan Eghtesad, Oscar Bronsther, William Irish, Adrian Casavilla, Kareem Abu-Elmagd, David Van Thiel, Andreas Tzakis, John J. Fung, Thomas E. Starzl
Journal: Hepatology (1994)

One thousand one hundred and twenty-eight candidates for liver transplantation were stratified into five urgency-of-need categories by the United Network for Organ Sharing (UNOS) criteria. Most patients of low-risk UNOS 1 status remained alive after 1 yr without transplantation; the mortality while waiting was 3% after a median of 229.5 days. In contrast, only 3% of those entered at the highest risk UNOS 5 category survived without transplantation; 28% died while waiting, the deaths occurring at a median of 5.5 days. The UNOS categories in between showed the expected gradations, in which at each higher level fewer patients remained as candidates throughout the 1-yr duration of study while progressively more died at earlier and earlier times while waiting for an organ. In a separate study of posttransplantation survival during the same time period, the best postoperative results were in the lowest-risk UNOS 1 and 2 patients (88% combined), and the worst results were those in UNOS 5 (71%). However, a relative risk cross-analysis showed that a negative benefit of transplantation may have been the result in terms of 1-yr survival for the low-risk elective patients, but that a gain in life extension was achieved in the potentially lethal UNOS categories 3, 4 and 5 (greatest for UNOS 3). These findings and conclusions are discussed in terms of total care of patients with liver disease, and in the context of organ allocation policies of the United States and Europe.
Uptake of immunisation against hepatitis B among surgeons in Wessex Regional Health Authority.
Authors: J R Williams, A D Flowerdew
Journal: BMJ (1990)

CommentWe found a small but significant increase in methaemoglobin concentration in 1-6 year old children after routine administration of 5 g of prilocaine- lignocaine cream before surgery.Although the peak methaemoglobin concentration observed was well within safe limits, the finding of an increased concentration 24 hours after administration suggests that cumulative effects may occur in children receiving the cream daily.Some of these may be at special risk owing to pre-existing anaemia, coadministration of sulphonamide antibiotics, or reduced renal excretion of metabolites of prilocaine.The minimum effective dose should be used in all children requiring daily applications of prilocaine-lignocaine cream.
Prognostic Significance of Pretreatment Serum Cytokines in Classical Hodgkin Lymphoma
Authors: Preethi Reddy Marri, Lucy S. Hodge, Matthew J. Maurer, Steven C. Ziesmer, Susan L. Slager, Thomas M. Habermann, Brian K. Link, James R. Cerhan, Anne J. Novak, Stephen M. Ansell
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Although the International Prognostic Score (IPS) is the gold standard for risk-stratifying patients with classical Hodgkin lymphoma (cHL), these criteria do not accurately predict outcome. As cytokines are critically involved in driving cHL, we tested whether pretreatment serum cytokine levels could provide additional prognostic information. Experimental Design: Thirty cytokines were measured in pretreatment serum from 140 patients with cHL and compared with 50 nonlymphoma controls. Patients were followed for event-free survival (EFS) and overall survival (OS), and Cox proportional hazards regression models were used to assess the association of individual cytokines and the cytokine profiles with outcome via unadjusted and IPS-adjusted HR. Results: Twelve cytokines (EGF, bFGF, G-CSF, HGF, IL-6, IL-8, IL-12, IL-2R, IP-10, MIG, TNF-α, and VEGF) were significantly (P &amp;lt; 0.05) higher in patients with cHL than controls; elevated levels of HGF, IL-6, IL-2R, IP-10, and MIG were all associated with poorer EFS. Only interleukin-2 receptor (IL-2R; P = 0.002) and interleukin (IL)-6 (P &amp;lt; 0.001) were independently prognostic. Patients with increased IL-6 and IL-2R had a significantly higher risk of early relapse and death, a finding that remained significant even after IPS-based risk stratification. Although elevated IL-6 and IL-2R correlated with the IPS, soluble CD30 (sCD30), and thymus and activation-related chemokine (TARC) levels, the two-cytokine model remained independently predictive of prognosis. Conclusions: Elevated pretreatment serum cytokines are associated with increased disease relapse and inferior survival in cHL. Thus, the pretreatment cytokine profile, particularly serum levels of IL-6 and IL-2R, may be used to identify patients with cHL at high risk for early-disease relapse. Clin Cancer Res; 19(24); 6812–9. ©2013 AACR.
Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens
Authors: Krzysztof Kiryluk, Yifu Li, Francesco Scolari, Simone Sanna-Cherchi, Murim Choi, Miguel Verbitsky, David Fasel, Sneh Lata, Sindhuri Prakash, Samantha Shapiro, Clara Fischman, Holly J Snyder, Gerald Appel, Claudia Izzi, Battista Fabio Viola, Nadia Dallera, Lucia Del Vecchio, Cristina Barlassina, Erika Salvi, Francesca Eleonora Bertinetto, Antonio Amoroso, Silvana Savoldi, Marcella Rocchietti, Alessandro Amore, Licia Peruzzi, Rosanna Coppo, Maurizio Salvadori, Pietro Ravani, Riccardo Magistroni, Gian Marco Ghiggeri, Gianluca Caridi, Monica Bodria, Francesca Lugani, Landino Allegri, Marco Delsante, Mariarosa Maiorana, Andrea Magnano, Giovanni Frasca, Emanuela Boer, Giuliano Boscutti, Claudio Ponticelli, Renzo Mignani, Carmelita Marcantoni, Domenico Di Landro, Domenico Santoro, Antonello Pani, Rosaria Polci, Sandro Feriozzi, Silvana Chicca, Marco Galliani, Maddalena Gigante, Loreto Gesualdo, Pasquale Zamboli, Giovanni Giorgio Battaglia, Maurizio Garozzo, Dita Maixnerová, Vladimir Tesar, Frank Eitner, Thomas Rauen, Jürgen Floege, Tibor Kovacs, Judit Nagy, Krzysztof Mucha, Leszek Pączek, Marcin Zaniew, Małgorzata Mizerska-Wasiak, Maria Roszkowska-Blaim, Krzysztof Pawlaczyk, Daniel Gale, Jonathan Barratt, Lise Thibaudin, Francois Berthoux, Guillaume Canaud, Anne Boland, Marie Metzger, Ulf Panzer, Hitoshi Suzuki, Shin Goto, Ichiei Narita, Yasar Caliskan, Jingyuan Xie, Ping Hou, Nan Chen, Hong Zhang, Robert J Wyatt, Jan Novak, Bruce A Julian, John Feehally, Benedicte Stengel, Daniele Cusi, Richard P Lifton, Ali G Gharavi
Journal: Nature Genetics (2014)
Trends in Sensitisation to Aero and Food Allergens-Comparison between different Birth Cohorts
Authors: Taraneh Dean, C. Venter, R. Kurukuralaatchy, B. Pereira, S. Matthews, Jane Grundy, C.B. Clayton, M. Fenn, B. Higgins, Syed Hasan Arshad
Journal: Journal of Allergy and Clinical Immunology (2007)
A Worldwide Survey of Human Male Demographic History Based on Y-SNP and Y-STR Data from the HGDP-CEPH Populations
Authors: W. Shi, Q. Ayub, M. Vermeulen, R.-g. Shao, S. Zuniga, K. van der Gaag, P. de Knijff, M. Kayser, Y. Xue, C. Tyler-Smith
Journal: Molecular Biology and Evolution (2009)

We have investigated human male demographic history using 590 males from 51 populations in the Human Genome Diversity Project - Centre d'Étude du Polymorphisme Humain worldwide panel, typed with 37 Y-chromosomal Single Nucleotide Polymorphisms and 65 Y-chromosomal Short Tandem Repeats and analyzed with the program Bayesian Analysis of Trees With Internal Node Generation. The general patterns we observe show a gradient from the oldest population time to the most recent common ancestors (TMRCAs) and expansion times together with the largest effective population sizes in Africa, to the youngest times and smallest effective population sizes in the Americas. These parameters are significantly negatively correlated with distance from East Africa, and the patterns are consistent with most other studies of human variation and history. In contrast, growth rate showed a weaker correlation in the opposite direction. Y-lineage diversity and TMRCA also decrease with distance from East Africa, supporting a model of expansion with serial founder events starting from this source. A number of individual populations diverge from these general patterns, including previously documented examples such as recent expansions of the Yoruba in Africa, Basques in Europe, and Yakut in Northern Asia. However, some unexpected demographic histories were also found, including low growth rates in the Hazara and Kalash from Pakistan and recent expansion of the Mozabites in North Africa.
Late ventricular arrhythmias during acute regional ischemia in the isolated blood perfused pig heart Role of electrical cellular coupling
Authors: J de Groot
Journal: Cardiovascular Research (2001)

Objective: Acute ischemia comes with two phases of life-threatening arrhythmias, early (within 10 minutes, 1A) and late (after about 15 minutes, 1B). The mechanism of the latter is unknown and in this paper, we test the hypothesis that a phase of intermediate coupling between surviving epicardium and inexcitable midmyocardium underlies 1B arrhythmias. Methods: Pig hearts (n = 26) were retrogradely perfused with a blood Tyrode's mixture. The left anterior descending artery was occluded. We investigated (1) inducibility of ventricular fibrillation (VF) with programmed stimulation, (2) tissue impedance (Rt) heterogeneity within the ischemic zone, (3) multiple subepicardial and midmyocardial electrograms, (4) subepicardial lactate dehydrogenase (LDH) and glycogen content. Results: In nine of ten hearts, one—three premature stimuli caused VF between 14 and 53 min of ischemia. This typically happened when the Rt of the ischemic zone had increased up to 40% of its final value. More uncoupling terminated the period of VF inducibility. The excitability of the surviving subepicardial layer was depressed during the same period with partial uncoupling, but recovered when the uncoupling from the midmyocardium had progressed further. Conclusions: We show that 1B-VF can be induced within a distinct time window and coincides with a distinct range of Rt rise. Subepicardium is electrically depressed, presumably through coupling with midmyocardium, complete uncoupling causes subepicardial recovery and terminates the substrate for 1B-VF. Hence, we suggest that the substrate for 1B-VF consists of intermediate coupling of subepicardium and midmyocardium.
Baby Food Exchanges and Feeding the Diabetic Infant
Authors: Marian M Benz, Elaine Kohler
Journal: Diabetes Care (1980)

Because of the dangers of hypoglycemia to the developing brain, the need to develop a lifelong positive attitude toward an eating pattern, the inherent communication difficulties, and the spontaneity of the very young, the diabetic infant presents a particular challenge to medical personnel. Baby and toddler foods in jar measurements and formula have been translated into the American Diabetes Association exchanges to help in teaching families with diabetic infants the effects of various foods on the infant's diabetes. The exchanges are taught as tools in maintaining metabolic balance rather than as a fixed diet. Caloric level is planned on the basis of diet history and the infant's current growth status. Flexibility of pattern and attitude is emphasized to minimize conflict over eating and to allow normal spontaneous activity without jeopardizing health.
Lung and chest wall mechanics in normal anaesthetized subjects and in patients with COPD at different PEEP levels
Authors: G Musch, G Foti, M Cereda, P Pelosi, D Poppi, A Pesenti
Journal: European Respiratory Journal (1997)

In order to assess the relative contribution of the lung and the chest wall to the derangements of respiratory mechanics in chronic obstructive pulmonary disease (COPD) patients with acute ventilatory failure (AVF), we studied eight COPD patients undergoing controlled mechanical ventilation for AVF and nine normal subjects anaesthetized for surgery as a control group. With the use of the interrupter technique together with the oesophageal balloon technique we measured: static lung and chest wall elastances (E[st,L] and E[st,w], respectively), maximum (R[L,max]), minimum (R[L,min]) and additional (deltaR[L]) lung resistances, additional chest wall resistance (deltaRw) and, in the COPD group, total intrinsic positive end-expiratory pressure (PEEPtot). Measurements were repeated at 0, 5, 10 and 15 cmH2O of applied positive end-expiratory pressure (PEEP). We found that, in the COPD group: 1) both E(st,w) and deltaRw were higher than in the normal group; 2) R(L,max) was markedly increased due to an increase of both R(L,min) and deltaRL; 3) even low levels of PEEP increased PEEPtot; 4) PEEP did not reduce elastance or total resistance of either the lung or the chest wall. We conclude that chest wall mechanics are abnormal in chronic obstructive pulmonary disease patients with acute ventilatory failure undergoing controlled mechanical ventilation and that positive end-expiratory pressure does not seem to be effective in reducing either elastance or resistance of the lung or chest wall.
Chimeric GB virus B genomes containing hepatitis C virus p7 are infectious in vivo
Authors: Stephen Griffin, Rachel Trowbridge, Pia Thommes, Nigel Parry, David Rowlands, Mark Harris, Helen Bright
Journal: Journal of Hepatology (2008)

The development of new therapies for hepatitis C virus (HCV) infection has been hampered by the lack of a small animal model. GB virus B (GBV-B), which infects new world monkeys, has been proposed as a surrogate system for HCV replication. Despite their short genetic distance, however, difficulties exist when extrapolating results from GBV-B to the HCV system. One way of addressing this is the creation of chimeric GBV-B containing HCV elements.Construction and analysis of GBV-B chimeras in which the p13 ion channel was replaced by its HCV counterpart, p7.Replacing all, or part of, the GBV-B p13 protein with HCV p7 resulted in viable chimeras which replicated at wild-type levels in marmosets following intra-hepatic RNA injection. Serum from one animal injected with chimeric RNA was infectious in three naïve recipients, indicating that chimeras formed fully infectious virions. Amantadine, which blocks the ion channel activity of both HCV and GBV-B proteins in vitro, also inhibited GBV-B replication in primary hepatocytes.These viruses highlight the potential for chimeric GBV-B in the development of HCV-specific therapies and will provide a means of developing HCV p7 as a therapeutic target.
Kinase suppressor of Ras-1 protects intestinal epithelium from cytokine-mediated apoptosis during inflammation
Authors: Fang Yan, Sutha K. John, Guinn Wilson, David S. Jones, M. Kay Washington, D. Brent Polk
Journal: Journal of Clinical Investigation (2004)

TNF plays a pathogenic role in inflammatory bowel diseases (IBDs), which are characterized by altered cytokine production and increased intestinal epithelial cell apoptosis. In vitro studies suggest that kinase suppressor of Ras-1 (KSR1) is an essential regulatory kinase for TNF-stimulated survival pathways in intestinal epithelial cell lines. Here we use a KSR1-deficient mouse model to study the role of KSR1 in regulating intestinal cell fate during cytokine-mediated inflammation. We show that KSR1 and its target signaling pathways are activated in inflamed colon mucosa. Loss of KSR1 increases susceptibility to chronic colitis and TNF-induced apoptosis in the intestinal epithelial cell. Furthermore, disruption of KSR1 expression enhances TNF-induced apoptosis in mouse colon epithelial cells and is associated with a failure to activate antiapoptotic signals including Raf-1/MEK/ERK, NF-κB, and Akt/protein kinase B. These effects are reversed by WT, but not kinase-inactive, KSR1. We conclude that KSR1 has an essential protective role in the intestinal epithelial cell during inflammation through activation of cell survival pathways.
A Fragment of Histidine-Rich Glycoprotein Is a Potent Inhibitor of Tumor Vascularization
Authors: Anna-Karin Olsson, Helena Larsson, Johan Dixelius, Irja Johansson, Chunsik Lee, Cornelia Oellig, Ingemar Björk, Lena Claesson-Welsh
Journal: Cancer Research (2004)

Abstract In this study, we show that recombinant human histidine-rich glycoprotein (HRGP) has potent antiangiogenic properties as judged from effects on a syngeneic tumor model in C57/bl6 mice. Growth of fibrosarcoma, a very aggressive tumor, was reduced by &amp;gt;60% by HRGP treatment, and tumor angiogenesis was dramatically decreased. Treatment with HRGP led to increased apoptosis and reduced proliferation in the tumors. In contrast, HRGP did not affect apoptosis or DNA synthesis in endothelial cells or tumor cells in vitro. The mechanism of action of HRGP involves rearrangement of focal adhesions and decreased attachment of endothelial cells to vitronectin and, as a consequence, reduced endothelial cell migration. By using truncated versions of HRGP, we demonstrate that the isolated 150 amino acid-residue His/Pro-rich domain, which is also released by spontaneous proteolysis from purified HRGP, mediates the inhibitory effect on chemotaxis. Moreover, the His/Pro-rich domain must be released from HRGP to exert its effect. This study shows for the first time inhibitory effects of HRGP on tumor vascularization in vivo, thus providing proof of concept that HRGP is an angiogenesis inhibitor.
Endothelin-1 plasma levels are not elevated in patients with obstructive sleep apnoea
Authors: F Grimpen, P Kanne, E. Schulz, G Hagenah, G Hasenfuβ, S Andreas
Journal: European Respiratory Journal (2000)

Endothelin-1 (ET-1), a potent vasoconstrictor, is released mainly by vascular endothelial cells under the influence of hypoxia and other stimuli. ET-1 is related to endothelial dysfunction, as well as arterial and pulmonary hypertension, all of which are thought to be associated with obstructive sleep apnoea (OSA). This study evaluated venous plasma concentrations of ET-1 and noradrenaline and 24-h systemic blood pressure in 29 patients with OSA (age=56.9+/-1.6 yrs; body mass index=29.5+/-0.7 kg x m2 (mean+/-SEM)). Blood samples were taken in the morning, evening and during sleep. In the same way, the patients were assessed during a night of continuous positive airway pressure (CPAP) and after 13.9+/-1.4 months while still on CPAP. ET-1 levels were compared to those of control subjects, who were selected from in- and outpatients and were matched to patients for age, sex, presence of arterial hypertension and coronary artery disease. ET-1 plasma levels were not elevated in the patients compared to the controls (41.6+/-2.2 and 44.9+/-1.3 pg x mL(-1), respectively, p=0.20). The ET-1 concentration did not change significantly, neither during sleep nor in the first night on CPAP therapy, nor under long-term treatment with CPAP. ET-1 neither correlated to the severity of OSA nor to that of systemic hypertension. The results suggest that endothelin-1 does not play a crucial role in the pathophysiology of obstructive sleep apnoea.
p53-Dependent Regulation of Mitochondrial Energy Production by the RelA Subunit of NF-κB
Authors: Renée F. Johnson, Ini-Isabée Witzel, Neil D. Perkins
Journal: Cancer Research (2011)

Aberrant activity of the nuclear factor kappaB (NF-κB) transcription factor family, which regulates cellular responses to stress and infection, is associated with many human cancers. In this study, we define a function of NF-κB in regulation of cellular respiration that is dependent upon the tumor suppressor p53. Translocation of the NF-κB family member RelA to mitochondria was inhibited by p53 by blocking an essential interaction with the HSP Mortalin. However, in the absence of p53, RelA was transported into the mitochondria and recruited to the mitochondrial genome where it repressed mitochondrial gene expression, oxygen consumption, and cellular ATP levels. We found mitochondrial RelA function to be dependent on its conserved C-terminal transactivation domain and independent of its sequence-specific DNA-binding ability, suggesting that its function in this setting was mediated by direct interaction with mitochondrial transcription factors. Taken together, our findings uncover a new mechanism through which RelA can regulate mitochondrial function, with important implications for how NF-κB activity and loss of p53 can contribute to changes in tumor cell metabolism and energy production.
Reactive oxygen species limit neutrophil life span by activating death receptor signaling
Authors: Dagmar Scheel-Toellner, Keqing Wang, Rachel Craddock, Paul R. Webb, Helen M. McGettrick, Lakhvir Kaur Assi, Neal Parkes, Louise E. Clough, Erich Gulbins, Mike Salmon, Janet M. Lord
Journal: Blood (2004)
Haemodynamic results of replacement of mitral and aortic valves with autologous fascia lata prostheses
Authors: P. H. Talavlikar, P. R. Walbaum, A. H. Kitchin
Journal: Thorax (1973)

Twelve patients undergoing aortic and 28 undergoing mitral valve replacement with autologous fascia lata valves were studied before and six months after surgery. One aortic and 10 mitral valves were found to be significantly incompetent. Of the incompetent mitral valves, two appeared to have perivalvular leaks. Six of the remainder were associated with abnormal ventricular filling patterns. Valve failure was much less common when the design was modified to provide a loose cusp structure; out of 12 such valves none was incompetent. Transvalvular gradients persist with fascial valves though they are lower than with most mechanical prostheses. Ventricular function was greatly improved in successful aortic replacement but remained impaired in the case of mitral replacement. Valve failure appeared to be associated with, or accelerated by, haemodynamic stress rather than due to inevitable degenerative pathological processes.
Myocardial hypertrophy in the absence of external stimuli is induced by angiogenesis in mice
Authors: Daniela Tirziu, Emmanuel Chorianopoulos, Karen L. Moodie, Robert T. Palac, Zhen W. Zhuang, Marc Tjwa, Carmen Roncal, Ulf Eriksson, Qiangwei Fu, Arye Elfenbein, Amy E. Hall, Peter Carmeliet, Lieve Moons, Michael Simons
Journal: Journal of Clinical Investigation (2007)

Although studies have suggested a role for angiogenesis in determining heart size during conditions demanding enhanced cardiac performance, the role of EC mass in determining the normal organ size is poorly understood. To explore the relationship between cardiac vasculature and normal heart size, we generated a transgenic mouse with a regulatable expression of the secreted angiogenic growth factor PR39 in cardiomyocytes. A significant change in adult mouse EC mass was apparent by 3 weeks following PR39 induction. Heart weight; cardiomyocyte size; vascular density normalization; upregulation of hypertrophy markers including atrial natriuretic factor, β-MHC, and GATA4; and activation of the Akt and MAP kinase pathways were observed at 6 weeks post-induction. Treatment of PR39-induced mice with the eNOS inhibitor l-NAME in the last 3 weeks of a 6-week stimulation period resulted in a significant suppression of heart growth and a reduction in hypertrophic marker expression. Injection of PR39 or another angiogenic growth factor, VEGF-B, into murine hearts during myocardial infarction led to induction of myocardial hypertrophy and restoration of myocardial function. Thus stimulation of vascular growth in normal adult mouse hearts leads to an increase in cardiac mass.