tbuckley/cabot-search huggingface dataset:
Plastid Genome Sequence of the Cryptophyte Alga Rhodomonas salina CCMP1319: Lateral Transfer of Putative DNA Replication Machinery and a Test of Chromist Plastid Phylogeny
Authors: H. Khan, N. Parks, C. Kozera, B. A. Curtis, B. J. Parsons, S. Bowman, J. M. Archibald
Journal: Molecular Biology and Evolution (2007)

Cryptophytes are a group of unicellular algae with chlorophyll c–containing plastids derived from the uptake of a secondary (i.e., eukaryotic) endosymbiont. Biochemical and molecular data indicate that cryptophyte plastids are derived from red algae, yet the question of whether or not cryptophytes acquired their red algal plastids independent of those in heterokont, haptophyte, and dinoflagellate algae is of long-standing debate. To better understand the origin and evolution of the cryptophyte plastid, we have sequenced the plastid genome of Rhodomonas salina CCMP1319: at 135,854 bp, it is the largest secondary plastid genome characterized thus far. It also possesses interesting features not seen in the distantly related cryptophyte Guillardia theta or in other red secondary plastids, including pseudogenes, introns, and a bacterial-derived gene for the tau/gamma subunit of DNA polymerase III (dnaX), the first time putative DNA replication machinery has been found encoded in any plastid genome. Phylogenetic analyses indicate that dnaX was acquired by lateral gene transfer (LGT) in an ancestor of Rhodomonas, most likely from a firmicute bacterium. A phylogenomic survey revealed no additional cases of LGT, beyond a noncyanobacterial type rpl36 gene similar to that recently characterized in other cryptophytes and haptophytes. Rigorous concatenated analysis of 45 proteins encoded in 15 complete plastid genomes produced trees in which the heterokont, haptophyte, and cryptophyte (i.e., chromist) plastids were monophyletic, and heterokonts and haptophytes were each other's closest relatives. However, statistical support for chromist monophyly disappears when amino acids are recoded according to their chemical properties in order to minimize the impact of composition bias, and a significant fraction of the concatenate appears consistent with a sister-group relationship between cryptophyte and haptophyte plastids.
The three major antigens on the surface of Plasmodium falciparum merozoites are derived from a single high molecular weight precursor.
Authors: A A Holder, R R Freeman
Journal: The Journal of Experimental Medicine (1984)

A 195,000 mol wt Plasmodium falciparum protein and processing fragments derived from it have been purified by monoclonal antibody affinity chromatography. A polyvalent antiserum has been raised against the purified protein and used to identify the terminal processing products associated with the merozoite. Three unique fragments of 83,000, 42,000, and 19,000 mol wt are present and they represent the major surface antigens of P. falciparum merozoites.
Tracheobronchial foreign bodies
Authors: JA Nakhosteen
Journal: European Respiratory Journal (1994)

The history of bronchology began with foreign body retrieval [1], which still remains a gratifying procedure occurring fairly rarely in routine practice, but with higher frequency in paediatric medicine and in adults with impaired airway protective mechanisms.Tracheobronchial foreign bodies have taken on a new dimension in interventional bronchology, with the placement, adjustment and removal of an increasing variety of stents, presenting problems of a very special nature.Certain fundamental considerations apply, however, in all these cases and these will be discussed here as a background for the paper on nonasphyxiating tracheobronchial foreign bodies by LAN [2] in this issue.
Year in review in intensive care medicine, 2005. II. Infection and sepsis, ventilator-associated pneumonia, ethics, haematology and haemostasis, ICU organisation and scoring, brain injury
Authors: Peter Andrews, Elie Azoulay, Massimo Antonelli, Laurent Brochard, Christian Brun-Buisson, Geoffrey Dobb, Jean-Yves Fagon, Herwig Gerlach, Johan Groeneveld, Jordi Mancebo, Philipp Metnitz, Stefano Nava, Jerome Pugin, Michael Pinsky, Peter Radermacher, Christian Richard, Robert Tasker
Journal: Intensive Care Medicine (2006)
RasV12-Mediated Down-regulation of CCAAT/Enhancer Binding Protein β in Immortalized Fibroblasts Requires Loss of p19Arf and Facilitates Bypass of Oncogene-Induced Senescence
Authors: Thomas Sebastian, Peter F. Johnson
Journal: Cancer Research (2009)

The transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) is involved in cellular responses to oncogenic and physiologic Ras signals. C/EBPbeta is required for premature senescence of primary mouse fibroblasts induced by expression of H-Ras(V12), demonstrating its role in oncogene-induced senescence. Here, we have investigated the mechanisms by which Ras inhibits proliferation of normal cells but transforms immortalized cells. We show that oncogenic Ras down-regulates C/EBPbeta expression in NIH 3T3 cells, which are immortalized by a deletion of the CDKN2A locus and, therefore, lack the p16(Ink4a) and p19(Arf) tumor suppressors. Ras(V12)-induced silencing of C/EBPbeta occurred at the mRNA level and involved both the Raf-mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase-ERK and phosphatidylinositol 3-kinase signaling pathways. Oncogenic Ras decreased C/EBPbeta expression in Ink4a/Arf(-/-) mouse embryo fibroblasts (MEF) but increased C/EBPbeta levels in wild-type MEFs. C/EBPbeta down-regulation in NIH 3T3 cells was reversed by expression of p19(Arf), but not of p53 or p16(Ink4a), highlighting a critical role for p19(Arf) in sustaining C/EBPbeta levels. Ectopic expression of p34 C/EBPbeta (LAP) inhibited Ras(V12)-mediated transformation of NIH 3T3 cells, suppressed their tumorigenicity in nude mice, and reactivated expression of the proapoptotic Fas receptor, which is also down-regulated by Ras. Our findings indicate that Cebpb gene silencing eliminates a growth inhibitory transcription factor that would otherwise restrain oncogenesis. We propose that C/EBPbeta is part of a p53-independent, p19(Arf)-mediated network that enforces Ras-induced cell cycle arrest and tumor suppression in primary fibroblasts.
Serum Protein Profiles to Identify Head and Neck Cancer
Authors: J. Trad Wadsworth, Kenneth D. Somers, Lisa H. Cazares, Gunjan Malik, Bao-Ling Adam, Brendan C. Stack, George L. Wright, O. John Semmes
Journal: Clinical Cancer Research (2004)

Abstract Purpose: New and more consistent biomarkers of head and neck squamous cell carcinoma (HNSCC) are needed to improve early detection of disease and to monitor successful patient management. The purpose of this study was to determine whether a new proteomic technology could correctly identify protein expression profiles for cancer in patient serum samples. Experimental Design: Surface-enhanced laser desorption/ionization-time of flight-mass spectrometry ProteinChip system was used to screen for differentially expressed proteins in serum from 99 patients with HNSCC and 102 normal controls. Protein peak clustering and classification analyses of the surface-enhanced laser desorption/ionization spectral data were performed using the Biomarker Wizard and Biomarker Patterns software (version 3.0), respectively (Ciphergen Biosystems, Fremont, CA). Results: Several proteins, with masses ranging from 2,778 to 20,800 Da, were differentially expressed between HNSCC and the healthy controls. The serum protein expression profiles were used to develop and train a classification and regression tree algorithm, which reliably achieved a sensitivity of 83.3% and a specificity of 100% in discriminating HNSCC from normal controls. Conclusions: We propose that this technique has potential for the development of a screening test for the detection of HNSCC.
Somatic RHOA mutation in angioimmunoblastic T cell lymphoma
Authors: Mamiko Sakata-Yanagimoto, Terukazu Enami, Kenichi Yoshida, Yuichi Shiraishi, Ryohei Ishii, Yasuyuki Miyake, Hideharu Muto, Naoko Tsuyama, Aiko Sato-Otsubo, Yusuke Okuno, Seiji Sakata, Yuhei Kamada, Rie Nakamoto-Matsubara, Nguyen Bich Tran, Koji Izutsu, Yusuke Sato, Yasunori Ohta, Junichi Furuta, Seiichi Shimizu, Takuya Komeno, Yuji Sato, Takayoshi Ito, Masayuki Noguchi, Emiko Noguchi, Masashi Sanada, Kenichi Chiba, Hiroko Tanaka, Kazumi Suzukawa, Toru Nanmoku, Yuichi Hasegawa, Osamu Nureki, Satoru Miyano, Naoya Nakamura, Kengo Takeuchi, Seishi Ogawa, Shigeru Chiba
Journal: Nature Genetics (2014)
Checkpoints couple transcription network oscillator dynamics to cell-cycle progression
Authors: Sara L Bristow, Adam R Leman, Laura A Simmons Kovacs, Anastasia Deckard, John Harer, Steven B Haase
Journal: Genome biology (2014)

Abstract Background The coupling of cyclin dependent kinases (CDKs) to an intrinsically oscillating network of transcription factors has been proposed to control progression through the cell cycle in budding yeast, Saccharomyces cerevisiae . The transcription network regulates the temporal expression of many genes, including cyclins, and drives cell-cycle progression, in part, by generating successive waves of distinct CDK activities that trigger the ordered program of cell-cycle events. Network oscillations continue autonomously in mutant cells arrested by depletion of CDK activities, suggesting the oscillator can be uncoupled from cell-cycle progression. It is not clear what mechanisms, if any, ensure that the network oscillator is restrained when progression in normal cells is delayed or arrested. A recent proposal suggests CDK acts as a master regulator of cell-cycle processes that have the potential for autonomous oscillatory behavior. Results Here we find that mitotic CDK is not sufficient for fully inhibiting transcript oscillations in arrested cells. We do find that activation of the DNA replication and spindle assembly checkpoints can fully arrest the network oscillator via overlapping but distinct mechanisms. Further, we demonstrate that the DNA replication checkpoint effector protein, Rad53, acts to arrest a portion of transcript oscillations in addition to its role in halting cell-cycle progression. Conclusions Our findings indicate that checkpoint mechanisms, likely via phosphorylation of network transcription factors, maintain coupling of the network oscillator to progression during cell-cycle arrest.
Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed
Authors: Herbert I. Hurwitz, Nikhil Uppal, Stephanie A. Wagner, Johanna C. Bendell, J. Thaddeus Beck, Seaborn M. Wade, John J. Nemunaitis, Philip J. Stella, J. Marc Pipas, Zev A. Wainberg, Robert Manges, William M. Garrett, Deborah S. Hunter, Jason Clark, Lance Leopold, Victor Sandor, Richard S. Levy
Journal: Journal of Clinical Oncology (2015)

Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer.In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m(2) twice daily) or placebo plus capecitabine. The primary end point was overall survival (OS); secondary end points included progression-free survival, clinical benefit response, objective response rate, and safety. Prespecified subgroup analyses evaluated treatment heterogeneity and efficacy in patients with evidence of inflammation.In the intent-to-treat population (ruxolitinib, n = 64; placebo, n = 63), the hazard ratio was 0.79 (95% CI, 0.53 to 1.18; P = .25) for OS and was 0.75 (95% CI, 0.52 to 1.10; P = .14) for progression-free survival. In a prespecified subgroup analysis of patients with inflammation, defined by serum C-reactive protein levels greater than the study population median (ie, 13 mg/L), OS was significantly greater with ruxolitinib than with placebo (hazard ratio, 0.47; 95% CI, 0.26 to 0.85; P = .011). Prolonged survival in this subgroup was supported by post hoc analyses of OS that categorized patients by the modified Glasgow Prognostic Score, a systemic inflammation-based prognostic system. Grade 3 or greater adverse events were observed with similar frequency in the ruxolitinib (74.6%) and placebo (81.7%) groups. Grade 3 or greater anemia was more frequent with ruxolitinib (15.3%; placebo, 1.7%).Ruxolitinib plus capecitabine was generally well tolerated and may improve survival in patients with metastatic pancreatic cancer and evidence of systemic inflammation.
Articular and vascular manifestations of polymyalgia rheumatica.
Authors: M.I Bruk
Journal: Annals of the Rheumatic Diseases (1967)

Polymyalgia rheumatica is a syndrome encountered by no means infrequently in middle-aged and elderly people.It is characterized by pains and stiffness, which are more severe in the morning, are felt to be in the shoulder and hip girdle muscles and often in the spine and are usually associated with fatigue, malaise, anorexia, loss of weight, and depression.The most constant laboratory finding is a raised erythrocyte sedimentation rate (ESR), which is often elevated out of proportion to the demonstrable physical abnormalities.Historical Review This syndrome was first described by Bruce (1888), who reported five men, aged 60 to 74 years, who developed severe joint and muscle pains and stiffness associated with marked constitutional disturbance.He considered this to be a disease not previously described and named it 'senile rheumatic gout".Widespread interest in this disease, however, dates from the second world war; reports by Holst and
Expression of a MHC class II transgene determines both superantigenicity and susceptibility to mammary tumor virus infection.
Authors: C Pucillo, R Cepeda, R J Hodes
Journal: The Journal of Experimental Medicine (1993)

Milk-borne mouse mammary tumor virus (MMTV) is a type B retrovirus that induces mammary carcinoma. Infectious MMTV, as well as genomically integrated mouse mammary proviruses, encode superantigens that are recognized by T cells that express appropriate T cell receptor V beta products. To determine the relationship between the superantigenic property of milk-borne MMTV and its in vivo infectivity, mice which were either positive or negative for expression of a transgene-encoded E alpha E beta class II major histocompatibility complex (MHC) product were exposed to milk borne C3H MMTV. Superantigen-mediated deletion of V beta 14-expressing T cells occurred only in E alpha transgene-positive mice, indicating that the deletion was E alpha E beta dependent. When mice were analyzed for viral infection by assaying viral p28 in the milk of recipient females, significant p28 levels were found only in E alpha E beta transgene-positive mice. Similarly, the presence of C3H MMTV LTR mRNA in mammary glands, as detected by PCR, paralleled p28 levels. These findings indicate that E alpha expression or the E alpha-dependent T cell response to viral superantigen is causally related to susceptibility to MMTV infection, and that lack of a permissive class II product can protect mice from virus infection.
Simultaneous radiochemotherapy versus radiotherapy alone in advanced head and neck cancer: a randomized multicenter study.
Authors: T G Wendt, G G Grabenbauer, C M Rödel, H J Thiel, H Aydin, R Rohloff, T P Wustrow, H Iro, C Popella, A Schalhorn
Journal: Journal of Clinical Oncology (1998)

PURPOSE A prospective randomized multicenter trial was performed to evaluate the contribution of simultaneously administered chemotherapy (CT) and radiotherapy (RT) in previously untreated patients with unresectable stage III/IV head and neck cancer. PATIENTS AND METHODS Patients with locoregionally advanced head and neck cancer were treated either with RT alone (arm A) or simultaneous RT plus CT (RCT; arm B). RT was identical in both arms and administered in three courses with 13 fractions of 1.8 Gy each twice daily. During one course, from day 3 to 11, 23.4 Gy was delivered. In arm B, cisplatin (CDDP) 60 mg/m2, fluorouracil (5-FU) 350 mg/m2 by intravenous (i.v.) bolus, and leucovorin (LV) 50 mg/m2 by i.v. bolus were given on day 2, and 5-FU 350 mg/m2/24 hour by continuous infusion and LV 100 mg/m2/24 hours by continuous infusion were given from day 2 to 5. Treatment was repeated on days 22 and 44; a total RT dose of 70.2 Gy was administered. Treatment breaks were scheduled from days 12 to 21 and days 34 to 43. RESULTS From 1989 to 1993, 298 patients were enrolled and 270 patients were assessable. Acute mucositis grade 3 or 4 was more frequent in arm B (38%) than in arm A (16%) (P &lt; .001). Total treatment time was significantly longer in arm B than in arm A (P &lt; .001) due to prolonged breaks. According to hematologic toxicity, scheduled drug doses were given in 74% of patients for the second course and 46% for the third course. The 3-year overall survival rate was 24% in arm A and 48% in arm B (P &lt; .0003). The 3-year locoregional control rate was 17% in arm A and 36% in arm B (P &lt; .004). Both arms showed similar distant failure patterns (arm A, 13 of 140; arm B, 12 of 130). Serious late side effects were not significantly different between treatment arms (arm A, 6.4%; arm B, 10%; not significant). CONCLUSION Concomitant CT offered improved disease control and survival in advanced head and neck cancer patients. Due to increased acute toxicity, more supportive care is demanded when CT is given simultaneously. Increased total treatment time does not exert a negative impact on outcome in this combined modality regimen.
Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.
Authors: N W Morrell, E N Atochina, K G Morris, S M Danilov, K R Stenmark
Journal: Journal of Clinical Investigation (1995)

Previous studies suggest that while lung angiotensin converting enzyme (ACE) activity is reduced during chronic hypoxia, inhibitors of ACE attenuate hypoxic pulmonary hypertension. In an attempt to explain this paradox we investigated the possibility that whole lung ACE activity may not reflect local pulmonary vascular ACE expression. The experimental approach combined in vivo hemodynamic studies in control and chronically hypoxic rats, measurement of whole lung ACE activity, and evaluation of local pulmonary vascular ACE expression by in situ hybridization and immunohistochemistry. Total lung ACE activity was reduced to 50% of control activity by 5 d of hypoxia and remained low for the duration of the study. Immunohistochemistry showed a marked reduction of ACE staining in alveolar capillary endothelium. However, an increase in ACE staining was observed in the walls of small newly muscularized pulmonary arteries at the level of alveolar ducts and walls. In situ hybridization studies showed increased signal for ACE mRNA in the same vessels. Inhibition of ACE by captopril during chronic hypoxia attenuated pulmonary hypertension and markedly reduced distal muscularization of small pulmonary arteries. In addition, we demonstrated marked longitudinal variation in ACE expression along the normal pulmonary vasculature with the highest levels found in small muscular arteries associated with terminal and respiratory bronchioles. We conclude that local ACE expression is increased in the walls of small pulmonary arteries during the development of hypoxic pulmonary hypertension, despite a generalized reduction in alveolar capillary ACE expression, and we speculate that local arteriolar ACE may play a role in the vascular remodeling associated with pulmonary hypertension.
Effect of Exercise on Cardiac Output, Left Coronary Flow and Myocardial Metabolism in the Unanesthetized Dog
Authors: EDWARD M. KHOURI, DONALD E. GREGG, CLAUDIA R. RAYFORD
Journal: Circulation Research (1965)

Cardiac output, left coronary artery flow, central aortic blood pressure and myocardial metabolism have been studied in the intact unanesthetized dog during exercise. Cardiac output and left coronary artery flow increase 350 to 400% during moderately severe exercise. The primary mechanical determinant of this increase appears to be cardio-acceleration; the stroke volume and stroke coronary flow contribution is relatively mild. Myocardial oxygen usage increases 300% or more with only a small elevation of the percentage of extraction of oxygen. The large increase of coronary flow in the dog and the significant elevation in hematocrit supply the extra oxygen.
Renal Hamartoma Associated with Renal Cell (Grawitz) Tumor: Another Indication that Grawitz Tumors Are Carcinosarcomas
Authors: J.J.L. Govaerts, J.C. van Gooswilligen, G.P. Vooys, F.C.S. Ramaekers, C.J. Herman, F.M.J. Debruyne
Journal: European Urology (1987)
The isotropic fractionator provides evidence for differential loss of hippocampal neurons in two mouse models of Alzheimer's disease
Authors: Hannah Brautigam, John W Steele, David Westaway, Paul E Fraser, Peter H St George-Hyslop, Sam Gandy, Patrick R Hof, Dara L Dickstein
Journal: Molecular Neurodegeneration (2012)

Abstract Background The accumulation of amyloid beta (Aβ) oligomers or fibrils is thought to be one of the main causes of synaptic and neuron loss, believed to underlie cognitive dysfunction in Alzheimer’s disease (AD). Neuron loss has rarely been documented in amyloid precursor protein (APP) transgenic mouse models. We investigated whether two APP mouse models characterized by different folding states of amyloid showed different neuronal densities using an accurate method of cell counting. Findings We examined total cell and neuronal populations in Swedish/Indiana APP mutant mice (TgCRND8) with severe Aβ pathology that includes fibrils, plaques, and oligomers, and Dutch APP mutant mice with only Aβ oligomer pathology. Using the isotropic fractionator, we found no differences from control mice in regional total cell populations in either TgCRND8 or Dutch mice. However, there were 31.8% fewer hippocampal neurons in TgCRND8 compared to controls, while no such changes were observed in Dutch mice. Conclusions We show that the isotropic fractionator is a convenient method for estimating neuronal content in milligram quantities of brain tissue and represents a useful tool to assess cell loss efficiently in transgenic models with different types of neuropathology. Our data support the hypothesis that TgCRND8 mice with a spectrum of Aβ plaque, fibril, and oligomer pathology exhibit neuronal loss whereas Dutch mice with only oligomers, showed no evidence for neuronal loss. This suggests that the combination of plaques, fibrils, and oligomers causes more damage to mouse hippocampal neurons than Aβ oligomers alone.