tbuckley/cabot-search huggingface dataset:
A foreign view
Authors: J Rodes
Journal: Gut (1991)

The creation of the Liver Unit at King's College Hospital Medical School by Roger Williams signified a historical landmark for hepatology in the United Kingdom, Europe, and the rest of the world.The scientific contribution of the Liver Unit at King's has been very important and of extraordinary quality.The topics investigated on the liver have been many, however, but in my opinion, acute hepatic failure, liver transplantation, immunology, and the liver and portal hypertension and its consequences, stand out among others.Without a doubt research on acute hepatic failure and the construction of an intensive care unit devoted exclusively to the treatment of this very grave disease allowed a better understanding of different complications of this syndrome.In this sense, the development and application of artificial liver support was to be praised.The increased knowledge of this syndrome has today allowed liver transplantation in these patients to be indicated on a more rational and scientific basis, up to the point where transplantation can be a truly efficient treatment for this clinical condition.The Liver Unit at King's in close collaboration with Professor Roy Calne from Cambridge were, together with Dr T Starlz of the United States, the pioneers of liver transplantation.Both Roger Williams and Roy Calne fearlessly faced the first difficult years of liver transplantation with scientific rigor.I am sure that I am not exaggerating when I say that most European hepatologists have looked to the Liver Unit at King's to establish a successful liver transplant programme.The application of the knowledge of modem immunology in the study of hepatic diseases has been another great scientific contribution by the Liver Unit.
A computational investigation of kinetoplastid trans-splicing.
Authors: Shuba Gopal, Saria Awadalla, Terry Gaasterland, George AM Cross
Journal: Genome biology (2005)

Abstract Trans -splicing is an unusual process in which two separate RNA strands are spliced together to yield a mature mRNA. We present a novel computational approach which has an overall accuracy of 82% and can predict 92% of known trans -splicing sites. We have applied our method to chromosomes 1 and 3 of Leishmania major , with high-confidence predictions for 85% and 88% of annotated genes respectively. We suggest some extensions of our method to other systems.
Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma
Authors: Mark Kirschbaum, Paul Frankel, Leslie Popplewell, Jasmine Zain, Maria Delioukina, Vinod Pullarkat, Deron Matsuoka, Bernadette Pulone, Arnold J. Rotter, Igor Espinoza-Delgado, Auayporn Nademanee, Stephen J. Forman, David Gandara, Edward Newman
Journal: Journal of Clinical Oncology (2011)

We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma.In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability.All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue.Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.
Loss of stem cell repopulating ability upon transplantation. Effects of donor age, cell number, and transplantation procedure.
Authors: D E Harrison, C M Astle
Journal: The Journal of Experimental Medicine (1982)

Long-term functional capacities of marrow cell lines were defined by competitive repopulation, a technique capable of detecting a small decline in repopulating abilities. There was little or no difference between cells from old and young donors, but a single serial transplantation caused a large decline in repopulating ability. Varying the numbers of marrow cells transplanted into the initial carrier from 10(5) to 10(7) did not alter the ability of the carrier's marrow cells to repopulate in competition with previously untransplanted cells. This ability was improved only in carriers that had received 10(8) marrow cells, although deleterious effects of transplantation were still present. These effects were not solely caused by cell damage from the transplantation procedure, because transplantation by parabiosis, or recovery from sublethal irradiation without transplantation, reduced repopulating abilities as much as transplanting 10(5) to 10(7) marrow cells. The transplantation effect also was not caused solely by irradiation, because the same effect appeared in unirradiated W/Wv carriers. The transplantation effect was more pronounced when donors were identified by hemoglobin type than by chromosome markers, implying that nonerythroid cell lines may be less affected by transplantation than erythroid precursor cells. When the effects of a lifetime of normal function and a single transplantation were compared, the latter caused 3-7 times more decline in repopulating abilities of phytohemagglutinin-responsive cell precursors, and at least 10-20 times more decline in erythroid cell precursors. Stem cell lines can be serially transplanted at least five times before losing their ability to repopulate and save lethally irradiated recipients or to cure genetically anemic mice. Therefore, if transplantation causes an acceleration of the normal aging process, these figures suggest that stem cells should be able to function normally through at least 15-50 life spans.
Is Europe ready to reach tuberculosis elimination? An outbreak report from Southern Italy
Authors: Laura Gillini, Rosella Centis, Lia D'Ambrosio, Alberto Fedele, Valerio Aprile, Giancarlo Pasanisi, Leonardo Donateo, Danila Costa, Giovanni Battista Migliori, Paolo Tundo
Journal: European Respiratory Journal (2015)

In July 2014, in Rome, the European Respiratory Society and the World Health Organization (WHO) developed a global framework for tuberculosis (TB) elimination in low TB incidence countries, focussed on the concept of TB elimination (fewer than one TB case per million population) [1–5]. Recent studies demonstrated that several "areas" relevant for TB elimination are not fully covered in Europe and in Italy [6, 7]. Managing tuberculosis outbreaks in Southern Italy is difficult, hampering elimination efforts <http://ow.ly/JE7dy>
Genomewide linkage scan of hand osteoarthritis in female twin pairs showing replication of quantitative trait loci on chromosomes 2 and 19
Authors: G. Livshits, B. S Kato, G. Zhai, D. J Hart, D. Hunter, A. J MacGregor, F. M K Williams, T. D Spector
Journal: Annals of the Rheumatic Diseases (2006)

Until recently, there has been little agreement between conflicting results of osteoarthritis (OA) linkage. The purpose of this study was to conduct a whole-genome linkage scan to identify susceptibility loci for idiopathic hand OA in a large, population-based sample of females.Two OA-related radiographic phenotypes DIP (distal interphalangeal joints)-OA and Tot-KL (Kellgren-Lawrence score for both hands) chosen a priori were examined on 538 (269 pairs) monozygous and 1256 (628 pairs) dizygous (DZ) females. A genome-wide scan using microsatellite markers spaced 10 cM apart was performed on 1028 DZ twins. First, the heritability of the two OA phenotypes was estimated. Next, multipoint linkage analysis was conducted using a modified version of the Haseman-Elston method in a generalised linear model.Heritability for DIP-OA and Tot-KL was found to be 47.6% and 67.4%, respectively. A genome-wide scan produced reliable evidence of significant linkage of DIP-OA on chromosome 2 at 90 cM (logarithmic odds ratio (LOD) = 2.90) and for Tot-KL on chromosome 19 at 65 cM (LOD = 4.26). These results are in agreement with data published previously. Several other significant linkage peaks were observed-for example, on chromosome 1 at 250 cM and on chromosome 3 at 30 cM-but were confirmed less reliably.This is one of the largest OA linkage studies performed to date and provides clear evidence for linkage at two quantitative trait loci (on chromosome 2 at 90 cM and on chromosome 19 at 65 cM). As the results were robust and replicated in previous smaller studies, the fine mapping of these regions is a logical next step to pinpoint potential susceptibility gene(s) of interest.
Association of Sexual Violence and Human Rights Violations With Physical and Mental Health in Territories of the Eastern Democratic Republic of the Congo
Authors: Kirsten Johnson
Journal: JAMA (2010)

<h3>Context</h3>Studies from the Eastern Region of the Democratic Republic of the Congo (DRC) have provided anecdotal reports of sexual violence. This study offers a population-based assessment of the prevalence of sexual violence and human rights abuses in specific territories within Eastern DRC.<h3>Objective</h3>To assess the prevalence of and correlations with sexual violence and human rights violations on residents of specific territories of Eastern DRC including information on basic needs, health care access, and physical and mental health.<h3>Design, Setting, and Participants</h3>A cross-sectional, population-based, cluster survey of 998 adults aged 18 years or older using structured interviews and questionnaires, conducted over a 4-week period in March 2010.<h3>Main Outcome Measures</h3>Sexual violence prevalence and characteristics, symptoms of major depressive disorder (MDD) and posttraumatic stress disorder (PTSD), human rights abuses, and physical and mental health needs among Congolese adults in specific territories of Eastern DRC.<h3>Results</h3>Of the 1005 households surveyed 998 households participated, yielding a response rate of 98.9%. Rates of reported sexual violence were 39.7% (95% confidence interval [CI], 32.2%-47.2%; n = 224/586) among women and 23.6% (95% CI, 17.3%-29.9%; n = 107/399) among men. Women reported to have perpetrated conflict-related sexual violence in 41.1% (95% CI, 25.6%-56.6%; n = 54/148) of female cases and 10.0% (95% CI, 1.5%-18.4%; n = 8/66) of male cases. Sixty-seven percent (95% CI, 59.0%-74.5%; n = 615/998) of households reported incidents of conflict-related human rights abuses. Forty-one percent (95% CI, 35.3%-45.8%; n = 374/991) of the represented adult population met symptom criteria for MDD and 50.1% (95% CI, 43.8%-56.3%; n = 470/989) for PTSD.<h3>Conclusion</h3>Self-reported sexual violence and other human rights violations were prevalent in specific territories of Eastern DRC and were associated with physical and mental health outcomes.
Effects of acetazolamide on overnight oxygenation and acute mountain sickness in patients with asthma
Authors: M Mirrakhlmov, N Brimkulov, J Cieslicki, M Tobiasz, Z Kudaiberdiev, I Moldotashev, G Shmidt, J Zielinski
Journal: European Respiratory Journal (1993)

The aim of the study was to assess effects of acetazolamide in prevention of acute mountain sickness (AMS) and on overnight oxygenation, in patients with asthma treated at the altitude of 3,200 m. Sixteen patients with asthma, 6 males and 10 females, mean age 32 yrs, were first investigated at low altitude (760 m). They presented with mild airways obstruction, normal arterial blood gases, and normal oxygenation at night studied by pulse oximetry. After initial investigations, patients were divided by random number into the treated (T) and control (C) groups of eight patients each. T group patients received acetazolamide, 750 mg daily for 2 days, before the ascent and on the first day at altitude (3,200 m). Symptoms of AMS developed in seven patients from group C and in three from group T. The overnight pulse oximetry, performed on the first night at altitude, revealed that group T patients had statistically higher (p < 0.05) initial, 91 vs 87%, mean, 90 vs 86%, and minimum, 84 vs 75%, arterial oxygen saturation than group C patients. Overnight pulse oximetry was repeated on the 5th, 10th and 17th day at altitude, and showed that in group C patients, from the 5th day onwards, oxygenation improved to the level observed in group T patients on the first night. We conclude that pretreatment with acetazolamide before the ascent prevented patients with asthma from developing symptoms of AMS, and alleviated acute changes in arterial oxygen saturation brought about by the high altitude hypoxia.
Diagnostic Role of the Atopy Patch Test in Children with Atopic Dermatitis and Food Allergy
Authors: L.M. Brunetti, R. Tesse, M. Lore, M. Leone, R. Procacci, O. Sillecchia, M. Mastronardi, D. Locantore, L. Armenio
Journal: Journal of Allergy and Clinical Immunology (2006)
Autophagy Is a Survival Mechanism of Acute Myelogenous Leukemia Precursors during Dual mTORC2/mTORC1 Targeting
Authors: Jessica K. Altman, Amy Szilard, Dennis J. Goussetis, Antonella Sassano, Marco Colamonici, Elias Gounaris, Olga Frankfurt, Francis J. Giles, Elizabeth A. Eklund, Elspeth M. Beauchamp, Leonidas C. Platanias
Journal: Clinical Cancer Research (2014)

To examine whether induction of autophagy is a mechanism of leukemic cell resistance to dual mTORC1/mTORC2 inhibitors in acute myelogenous leukemia (AML) leukemic progenitors.Combinations of different experimental approaches were used to assess induction of autophagy, including immunoblotting to detect effects on LC3II and p62/SQTM1 expression and on ULK1 phosphorylation, immunofluorescence, and electron microscopy. Functional responses were assessed using cell viability and apoptosis assays, and clonogenic leukemic progenitor assays in methylcellulose.We provide evidence that treatment of AML cells with catalytic mTOR inhibitors results in induction of autophagy, which acts as a regulatory mechanism to promote leukemic cell survival. Such induction of autophagy by dual mTORC1/mTORC2 inhibitors partially protects primitive leukemic precursors from the inhibitory effects of such agents and limits their activities. Simultaneous blockade of the autophagic process using chloroquine or by knockdown of ULK1 results in enhanced antileukemic responses.Dual targeting of mTORC2 and mTORC1 results in induction of autophagy in AML cells. Combinations of catalytic mTOR targeting agents and autophagy inhibitors may provide a unique approach to target primitive leukemic precursors in AML.
Firing Properties of Single Muscle Vasoconstrictor Neurons in the Sympathoexcitation Associated With Congestive Heart Failure
Authors: Vaughan G. Macefield, Bengt Rundqvist, Yrsa B. Sverrisdottir, B. Gunnar Wallin, Mikael Elam
Journal: Circulation (1999)

Congestive heart failure (CHF) in humans is associated with a marked sympathoexcitation, including an augmented muscle sympathetic nerve activity (MSNA) in intraneural multiunit recordings. In the present study, single-unit recording was used to evaluate whether the firing properties of individual muscle vasoconstrictor neurons can reveal underlying mechanisms for this increase in MSNA.Eight patients with CHF (NYHA class II to IV; left ventricular ejection fraction, 29+/-5%, mean+/-SEM) were studied. In standard multiunit recordings, MSNA burst incidence (bursts/100 heartbeats) ranged from 65% to 100% (88+/-5%). Using selective tungsten microelectrodes, we made recordings from 16 single muscle vasoconstrictor axons. Mean unit firing probability (ie, the percentage of cardiac intervals in which a single axon fired) was 54.5+/-5.2% (range, 21 to 89%), and mean firing frequency was 0.98+/-0.22 Hz (0.14 to 3.86 Hz), both of which were higher than seen previously in healthy subjects (P<0.001). Although single neurons occasionally generated multiple spikes per sympathetic burst, such multiple firing was rare and was not different from that seen in healthy subjects.An increased firing frequency of individual vasoconstrictor neurons is one mechanism for the increased number of multiunit MSNA bursts at rest in CHF. The neurons discharge in more diastoles than in healthy subjects (ie, firing probability is increased), but the likelihood of discharging >1 impulse per sympathetic burst is not increased. Despite the intense multiunit activity at rest, the firing characteristics of individual vasoconstrictor axons indicate a remaining capacity for transient increases of MSNA in CHF.
Evidence for the Chronic in Vivo Production of Human T Cell Leukemia Virus Type I Rof and Tof Proteins from Cytotoxic T Lymphocytes Directed against Viral Peptides
Authors: Claudine Pique, Abel Ureta-Vidal, Antoine Gessain, Bruno Chancerel, Olivier Gout, Riad Tamouza, Frantz Agis, Marie-Christine Dokhélar
Journal: The Journal of Experimental Medicine (2000)

Human T cell leukemia virus type I (HTLV-I) is a persistent virus that causes adult T cell leukemia and tropical spastic paraparesis/HTLV-I–associated myelopathy. Studies on rabbits have shown that viral proteins encoded by the open reading frames pX-I and pX-II are required for the establishment of the persistent infection. To examine the in vivo production of these proteins in humans, we have investigated whether cytotoxic T lymphocytes isolated from HTLV-I–infected individuals recognized pX-I and pX-II peptides. CD8+ T lymphocytes to pX-I and pX-II peptides were detected in HTLV-I–infected individuals, whatever their clinical status, and even in the absence of any antigenic restimulation. These findings indicate that the HTLV-I pX-I and pX-II proteins are chronically synthesized in vivo, and are targets of the natural immune response to the virus.
Initial Clinical Trial of Oral TAC-101, a Novel Retinoic Acid Receptor-Alpha Selective Retinoid, in Patients With Advanced Cancer
Authors: Naiyer A. Rizvi, John L. Marshall, Elizabeth Ness, Michael J. Hawkins, Craig Kessler, Helena Jacobs, Wayne D. Brenckman, Jin S. Lee, William Petros, Waun K. Hong, Jonathan M. Kurie
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The goals of this study were to determine the safety, toxicity, and pharmacokinetics of TAC-101, a novel synthetic retinoic acid receptor-alpha (RAR-α) selective retinoid, in patients with advanced cancer. PATIENTS AND METHODS: Twenty-nine patients at two centers received oral TAC-101 at doses ranging from 12 to 34 mg/m 2 /d. Pharmacokinetic sampling was performed on days 1 and 28. RESULTS: The most frequent toxicities were myalgia/arthralgia, fatigue, and triglyceridemia. No dose-limiting toxicities were observed within the first 28 days up to 28 mg/m 2 . However, seven of 21 patients experienced venous thromboembolic events (VTEs) during TAC-101 treatment. Eight additional patients who received 34 mg/m 2 were treated after a hypercoagulable work-up to exclude potential risk factors for VTE, and two of eight patients subsequently experienced VTEs. The maximum tolerated dose was exceeded at 34 mg/m 2 /d within the first 28 days, with one grade 3 hypertriglyceridemia, two grade 3 myalgia/arthralgia, and one grade 3 fatigue. One patient with advanced non–small-cell lung cancer had a complete response. No other responses were observed. No autoinduction of metabolism was observed with dosing over 28 days. CONCLUSION: This is the first human clinical study with TAC-101, a RAR-α selective retinoid. Musculoskeletal toxicity and hypertriglyceridemia were observed characteristics of previously studied retinoids. The recommended phase II dose is 24 mg/m 2 with this treatment schedule. Alternative treatment schedules and prospective evaluation of thrombotic risk will be investigated in subsequent studies.
Effects of Isoproterenol on Diaphragmatic Contractility in Septic Peritonitis
Authors: NAOYUKI FUJIMURA, SHINZOH SUMITA, EICHI NARIMATSU, YOSHITO NAKAYAMA, YASUO SHITINOHE, AKIYOSHI NAMIKI
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated the effects, and the mechanism of the effects, of isoproterenol on diaphragmatic contractility and fatigue in septic peritonitis in vitro. Ninety-six rats were divided into two groups of 48. One group (CLP group) was treated with cecal ligation and perforation (CLP) and the other (sham group) was treated with laparotomy. The left hemidiaphragm was removed at 16 h after the operation. We assessed the diaphragmatic contractility by twitch characteristics and force-frequency curves in vitro. Diaphragm fatigue was induced by rhythmically stimulating strips to contract at 60/ min (20 Hz, 0.33-s trains, 1 train/s) over a 4-min period. Force-frequency curves were determined before and after fatigue. Isoproterenol (10− 9, 10− 8, and 10− 7 M), a β -adrenoceptor agonist, was cumulatively administered to the organ bath. Isoproterenol significantly increased diaphragmatic contractility. There were no significant changes in diaphragmatic contractility in the sham group. Isoproterenol (10− 7 M) significantly accelerated diaphragmatic recovery of fatigue and increased cAMP levels both in the sham group and the CLP group. Propranolol (10− 7 M), a general β -adrenoceptor blocker, completely abolished the positive inotropic effect of isoproterenol (10− 7 M) and increased cAMP levels in the CLP group. Dibutyryl cAMP (10− 3 M), a derivative of cyclic AMP, mimicked the effects of isoproterenol in the CLP group. These results suggest that isoproterenol increases diaphragmatic contractility and accelerates diaphragmatic recovery of fatigue in septic peritonitis by activating the adenylate cyclase system. Fujimura N, Sumita S, Narimatsu E, Nakayama Y, Shitinohe Y, Namiki A. Effects of isoproterenol on diaphragmatic contractility in septic peritonitis.