tbuckley/cabot-search huggingface dataset:
Rapid Likelihood Analysis on Large Phylogenies Using Partial Sampling of Substitution Histories
Authors: A. P. J. de Koning, W. Gu, D. D. Pollock
Journal: Molecular Biology and Evolution (2009)

Likelihood-based approaches can reconstruct evolutionary processes in greater detail and with better precision from larger data sets. The extremely large comparative genomic data sets that are now being generated thus create new opportunities for understanding molecular evolution, but analysis of such large quantities of data poses escalating computational challenges. Recently developed Markov chain Monte Carlo methods that augment substitution histories are a promising approach to alleviate these computational costs. We analyzed the computational costs of several such approaches, considering how they scale with model and data set complexity. This provided a theoretical framework to understand the most important computational bottlenecks, leading us to combine novel variations of our conditional pathway integration approach with recent advances made by others. The resulting technique ("partial sampling" of substitution histories) is considerably faster than all other approaches we considered. It is accurate, simple to implement, and scales exceptionally well with dimensions of model complexity and data set size. In particular, the time complexity of sampling unobserved substitution histories using the new method is much faster than previously existing methods, and model parameter and branch length updates are independent of data set size. We compared the performance of methods on a 224-taxon set of mammalian cytochrome-b sequences. For a simple nucleotide substitution model, partial sampling was at least 10 times faster than the PhyloBayes program, which samples substitutions in continuous time, and about 100 times faster than when using fully integrated substitution histories. Under a general reversible model of amino acid substitution, the partial sampling method was 1,600 times faster than when using fully integrated substitution histories, confirming significantly improved scaling with model state-space complexity. Partial sampling of substitutions thus dramatically improves the utility of likelihood approaches for analyzing complex evolutionary processes on large data sets.
Orthopaedic surgery of the lower limbs in 49 802 rheumatoid arthritis patients: results from the Swedish National Inpatient Registry during 1987 to 2001
Authors: R J Weiss
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To analyse changes in the rates of hospital admission and use of orthopaedic surgery to the lower limbs in Swedish patients with rheumatoid arthritis between 1987 and 2001. <b>Methods:</b> Data for all rheumatoid patients admitted to hospital between 1987 and 2001 were abstracted from the Swedish National Hospital Discharge Register (SNHDR). The data in the register are collected prospectively, recording all inpatient admissions throughout Sweden. The SNHDR uses the codes for diagnoses at discharge and surgical procedures according to the Swedish version of the <i>International Classification of Diseases</i> (ICD). <b>Results:</b> In all, 49 802 individual patients with rheumatoid arthritis were identified, accounting for 159 888 inpatient visits. Hospital admissions for rheumatoid arthritis decreased by 42% (p&lt;0.001) during the period 1987 to 2001. Twelve per cent of all admissions were for a rheumatoid arthritis related surgical procedure to the lower limbs; those admissions decreased markedly (by 16%) between 1987 and 1996, and by 12% between 1997 and 2001, as did the overall number of rheumatoid arthritis related surgical procedures to the lower limbs during both time periods. Between 1997 and 2001, 47% of all rheumatoid arthritis related surgical procedures were total joint arthroplasties. There was an overall trend towards reduced length of hospital stay after orthopaedic surgery to the lower limbs during the study period. <b>Conclusions:</b> Rates of hospital admission and rheumatoid arthritis related surgical procedures to the lower limbs in Swedish patients with rheumatoid arthritis decreased between 1987 and 2001. This may reflect trends in disease severity, management, and health outcomes of this disease in Sweden.
Telomerase Activity in Lung Cancer Cells Obtained From Bronchial Washings
Authors: Naoyuki Yahata, Kazuma Ohyashiki, Junko H. Ohyashiki, Hiroshi Iwama, Shigefumi Hayashi, Keiko Ando, Keisuke Toyama, Takashi Hirano, Takaaki Tsuchida, Harubumi Kato, Jerry W. Shay
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: Telomerase, a ribonucleoprotein enzyme that functions in the maintenance of telomeres (specialized structures at the ends of chromosomes), has been reported to be a novel diagnostic marker for malignant diseases. We sought to determine whether measurement of telomerase activity in bronchial washings is of value in the diagnosis of lung cancer. Methods: Extracts of cells in bronchial washings were analyzed for telomerase activity by use of a telomeric repeat amplification protocol (TRAP) assay. Telomerase activity inside cells was evaluated by use of an in situ TRAP assay. The results of both TRAP assays were compared with those obtained from cytologic examination, which employed standard Papanicolaou staining. Results: When results from the two TRAP assays were combined, telomerase activity was detected in bronchial washings from 18 (82%; 95% confidence interval [CI] = 60%–95%) of 22 patients with lung cancer. In contrast, cancer cells were detected by cytologic examination in the bronchial washings of nine (41%; 95% CI = 21%–64%) of the same 22 patients, a statistically significant difference (two-sided P = .0061). In patients with lung cancer, telomerase-positive cells could be detected in bronchial washings irrespective of tumor location—11 of 14 (79%; 95% CI = 49%–95%) peripheral cancerous lesions and seven of eight (88%; 95% CI = 47%–100%) central cancerous lesions were detected by use of TRAP assays (for comparison,two-sidedP=.5349).Conclusions:Ahighpercentage of patients with lung cancers had detectable telomerase activity in bronchial washings. Thus, the use of a cell extractbased or an in situ TRAP assay in addition to cytologic examination may make the diagnosis of lung cancer more reliable.
Combination therapy for exercise intolerance in COPD
Authors: R Casaburi
Journal: Thorax (2006)

New combined approaches to reduce dynamic hyperinflation improve exercise intolerance in patients with COPD

Chronic obstructive pulmonary disease (COPD) is a miserable disease; exercise intolerance is one of its most troubling symptoms. Moreover, it has recently been discovered that poor exercise tolerance is highly predictive of poor survival. Those who care for these patients are therefore highly motivated to seek ways to ameliorate exercise intolerance. In recent years progress has come from what, at first glance, would seem to be an unlikely quarter. Although research expenditures for this disease are heavily weighted towards cell and molecular biology pursuits, physiological research (considered “old fashioned” in some quarters) has provided solid insights into rational treatment for exercise intolerance.

A key insight is that dynamic hyperinflation is a major mechanism limiting exercise tolerance in patients with COPD. This occurs when the increased metabolic requirements of exercise demand higher levels of pulmonary ventilation. This, in turn, requires that both tidal volume and respiratory rate increase. The patient with COPD is asked to exhale a larger volume in a shorter time, which becomes an impossible task given flow limitation imposed by the increased expiratory airflow resistance. At some point the exhalation cannot be completed in the allotted expiratory time, full exhalation cannot be accomplished, and end expiratory volume increases. Eventually, dynamic hyperinflation leads to end inspiratory lung volumes that approach a limiting value (total lung capacity). As the inspiratory reserve volume …
Evaluation of postprandial hyperemia in superior mesenteric artery and portal vein in healthy and cirrhotic humans: An operator-blind echo-Doppler study
Authors: Carlo Sabbá, Giovanna Ferraioli, Paul Genecin, Luis Colombato, Paolo Buonamico, Emanuel Lerner, Kenneth J. W. Taylor, Roberto J. Groszmann
Journal: Hepatology (1991)

In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and 12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity. (Hepatology 1991;13:714-718.)
<i>Mycobacterium tuberculosis</i> infection induces <i>il12rb1</i> splicing to generate a novel IL-12Rβ1 isoform that enhances DC migration
Authors: Richard T. Robinson, Shabaana A. Khader, Cynthia A. Martino, Jeffrey J. Fountain, Maria Teixeira-Coelho, John E. Pearl, Stephen T. Smiley, Gary M. Winslow, David L. Woodland, Michael J. Walter, Jose R. Conejo-Garcia, Ueli Gubler, Andrea M. Cooper
Journal: The Journal of Experimental Medicine (2010)

RNA splicing is an increasingly recognized regulator of immunity. Here, we demonstrate that after Mycobacterium tuberculosis infection (mRNA) il12rb1 is spliced by dendritic cells (DCs) to form an alternative (mRNA) il12rb1Δtm that encodes the protein IL-12Rβ1ΔTM. Compared with IL-12Rβ1, IL-12Rβ1ΔTM contains an altered C-terminal sequence and lacks a transmembrane domain. Expression of IL-12Rβ1ΔTM occurs in CD11c+ cells in the lungs during M. tuberculosis infection. Selective reconstitution of il12rb1−/− DCs with (mRNA) il12rb1 and/or (mRNA) il12rb1Δtm demonstrates that IL-12Rβ1ΔTM augments IL-12Rβ1-dependent DC migration and activation of M. tuberculosis-specific T cells. It cannot mediate these activities independently of IL12Rβ1. We hypothesize that M. tuberculosis-exposed DCs express IL-12Rβ1ΔTM to enhance IL-12Rβ1-dependent migration and promote M. tuberculosis–specific T cell activation. IL-12Rβ1ΔTM thus represents a novel positive-regulator of IL12Rβ1-dependent DC function and of the immune response to M. tuberculosis.
Characterization of Chemical Constituents in <i>Scutellaria baicalensis</i> with Antiandrogenic and Growth-Inhibitory Activities toward Prostate Carcinoma
Authors: Michael Bonham, Jeff Posakony, Ilsa Coleman, Bruce Montgomery, Julian Simon, Peter S. Nelson
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Botanical preparations are widely used by patients with prostate cancer. Scutellaria baicalensis, a botanical with a long history of medicinal use in China, was a constituent of the herbal mixture PC-SPES, a product that inhibited prostate cancer growth in both laboratory and clinical studies. Due to the difficulties encountered when evaluating the efficacy of complex natural products, we sought to identify active chemical constituents within Scutellaria and determine their mechanisms of action. Experimental Design and Results: We used high-performance liquid chromatography to fractionate S. baicalensis and identified four compounds capable of inhibiting prostate cancer cell proliferation; baicalein, wogonin, neobaicalein, and skullcapflavone. Comparisons of the cellular effects induced by the entire extract versus the four-compound combination produced comparable cell cycle changes, levels of growth inhibition, and global gene expression profiles (r2 = 0.79). Individual compounds exhibited antiandrogenic activities with reduced expression of the androgen receptor and androgen-regulated genes. In vivo, baicalein (20 mg/kg/d p.o.) reduced the growth of prostate cancer xenografts in nude mice by 55% at 2 weeks compared with placebo and delayed the average time for tumors to achieve a volume of ∼1,000 mm3 from 16 to 47 days (P &amp;lt; 0.001). Conclusions: Most of the anticancer activities of S. baicalensis can be recapitulated with four purified constituents that function in part through inhibition of the androgen receptor signaling pathway. We conclude that clinical studies evaluating the efficacy of these agents in the context of chemoprevention or the treatment of prostate cancer are warranted.
STUDIES ON THE HETEROLOGOUS IMMUNOGENICITY OF A METHANOL-INSOLUBLE FRACTION OF ATTENUATED TUBERCLE BACILLI (BCG)
Authors: David W. Weiss, Rose S. Bonhag, Patricia Leslie
Journal: The Journal of Experimental Medicine (1966)

A methanol-insoluble residue (MER) of phenol-killed attenuated tubercle bacilli (BCG), which has been reported previously to be capable of evoking heightened resistance to infection with antigenically unrelated microorganisms, was found to affect as well the resistance of highly inbred mice against tumor isografts. In most instances, the MER evoked heightened resistance against the tumor implants, but heightened susceptibility was the effect induced against two of the tumors tested, and no effect was elicited against one neoplasm. It is suggested that the heightened susceptibility occasionally produced by pretreatment with MER may also be of immunological nature, i.e. immunological enhancement. Treatment with MER was more effective when administered some time before tumor challenge than when given simultaneously with, or after, tumor implantation. The protective effects manifested against some tumors were of a high order, a significant number of animals rejecting the neoplastic implants, and were displayed even when several months elapsed between treatment and challenge. Living BCG and intact phenol-killed bacilli also evoked heightened resistance against some of the tumors tested, and in one experiment living BCG proved effective whereas MER did not. On the whole, however, MER was the most active (and least toxic, as shown previously) of the several tubercle bacillus preparations tested. MER elicited heightened reactivity against first transplant generation tumors as well as against tumors maintained for considerable periods of time by repeated animal passage, and against spontaneously arising as well as against induced neoplasms. The experimental parameters necessary to demonstrate maximal effects varied somewhat from tumor to tumor. In general, however, single intraperitoneal injections of small quantities of MER, of the order of 0.25 to 1.0 mg, afforded the best protection.
New Delhi Metallo-β-Lactamase–Producing Carbapenem-Resistant<i>Escherichia coli</i>Associated With Exposure to Duodenoscopes
Authors: Lauren Epstein, Jennifer C. Hunter, M. Allison Arwady, Victoria Tsai, Linda Stein, Marguerite Gribogiannis, Mabel Frias, Alice Y. Guh, Alison S. Laufer, Stephanie Black, Massimo Pacilli, Heather Moulton-Meissner, J. Kamile Rasheed, Johannetsy J. Avillan, Brandon Kitchel, Brandi M. Limbago, Duncan MacCannell, David Lonsway, Judith Noble-Wang, Judith Conway, Craig Conover, Michael Vernon, Alexander J. Kallen
Journal: JAMA (2014)

Carbapenem-resistant Enterobacteriaceae (CRE) producing the New Delhi metallo-β-lactamase (NDM) are rare in the United States, but have the potential to add to the increasing CRE burden. Previous NDM-producing CRE clusters have been attributed to person-to-person transmission in health care facilities.
Cooperation between proteolytic systems in cardiomyocyte recycling
Authors: O. Yamaguchi, M. Taneike, K. Otsu
Journal: Cardiovascular Research (2012)

Cardiomyocytes are terminally differentiated cells and thus do not have the ability to dilute damaged proteins and organelles by cell division. Thus, proteolytic and recycling systems within the cardiomyocyte are essential to maintain cardiac function. The major proteolytic systems in the cell are: the ubiquitin–proteasome system, autophagy, and calpain. The ubiquitin–proteasome system degrades specific proteins by labelling them with ubiquitin. Autophagy degrades cytosolic proteins and organelles; this is generally believed to be a non-specific type of degradation. Calpain is a Ca2+-sensitive cysteine protease that degrades intracellular substrates including cytoskeletal proteins, and participates in Ca2+-mediated intracellular processes. All three systems exist in the cardiomyocyte and play pivotal roles in maintaining cardiac function. However, there is still controversy regarding the role of each protein-degradation system in the heart. Our recent reports using cardiac-specific knockout mice have revealed the cardioprotective roles of autophagy and calpain in the development of heart failure. While these proteolytic systems exhibit distinct molecular mechanisms, they work cooperatively (one process can regulate another).
Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever.
Authors: G Husby, I van de Rijn, J B Zabriskie, Z H Abdin, R C Williams
Journal: The Journal of Experimental Medicine (1976)

46% of sera from 30 children with rheumatic chorea showed IgG antibody reacting with neuronal cytoplasm of human caudate and subthalamic nuclei. The antibody was also detected in 14% of 50 children with active rheumatic carditis. 55 normal control sera, as well as 148 sera from a broad variety of other disease states showed a low prevalence (1.8-4.0%) of positive reactions. In rheumatic chorea the presence of anti-neuronal antibody appeared to correlate with severity and duration of clinical attacks. Antibody reacting with neuronal cytoplasm was completely removed by absorption with Group A streptococcal membranes or with isolated human neurons from caudate nucleus. Partial absorption of antibody was also recorded using Group A cell wall preparations but not with Group A carbohydrate. No absorption of positive reactions was seen with streptococcal Group D membranes or cell walls. In rheumatic chorea, anti-neuronal antibody appeared to represent cross-reaction with antigens shared by Group A streptococcal membranes.
Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial
Authors: S. Andreas, C. Herrmann-Lingen, T. Raupach, L. Lüthje, J. A. Fabricius, N. Hruska, W. Körber, B. Büchner, C-P. Criée, G. Hasenfuß, P. Calverley
Journal: European Respiratory Journal (2006)

In chronic obstructive pulmonary disease (COPD), the sympathetic nervous system, as well as the renin–angiotensin system, is activated with possible negative systemic effects on skeletal muscles. Angiotensin II type-1 receptor blockers inhibit the sympathetic and renin–angiotensin systems and might improve skeletal and respiratory muscle strength in patients in whom these systems are activated. The effects of the angiotensin receptor blocker irbesartan given over 4 months was evaluated in 60 patients with COPD and a forced expiratory volume in one second of &lt;50% of the predicted value and without obvious cardiovascular disease that would necessitate the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Irbesartan was well tolerated, but did not exert a significant effect on the primary end-point maximum inspiratory pressure. Spirometric results were not affected, but total lung capacity was reduced. Irbesartan led to a significant decrease in haematocrit (46.4±3.6 to 43.9±4.3% versus 47.5±2.4 to 48.7±3.0% with placebo). In conclusion, respiratory muscle strength in chronic obstructive pulmonary disease patients was not influenced by angiotensin II receptor blockade. However, the changes in haematocrit and total lung capacity following irbesartan raise the possibility that well-known cardiovascular drugs can produce unanticipated beneficial effects in chronic obstructive pulmonary disease patients.
106 LONG TERM OUTCOME OF PATIENTS TRANSPLANTED FOR AUTOIMMUNE HEPATITIS—ANALYSIS OF THE EUROPEAN LIVER TRANSPLANT REGISTRY
Authors: C. Schramm, M. Bubenheim, J.G. O'Grady, J. Buckles, S. Pollard, P. Neuhaus, M. Manns, C. Broelsch, X. Rogiers, R. Adam, V. Karam, A. Lohse for Elita
Journal: Journal of Hepatology (2008)
Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant sprague-dawley rat
Authors: Hajime Takikawa, Naoyo Sano, Tohru Narita, Yoshinobu Uchida, Masami Yamanaka, Tohru Horie, Takashi Mikami, Osamu Tagaya
Journal: Hepatology (1991)

The hepatic transport of bile acid conjugates was studied in the Eisai hyperbilirubinuria rat, a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Serum bile acid levels were increased, bile acid-independent bile flow was decreased and biliary glutathione concentrations were markedly decreased in the Eisai hyperbilirubinuria rat. Biliary excretion of sulfobromophthalein was markedly impaired and almost no glutathione conjugate was excreted in the bile of the Eisai hyperbilirubinuria rat. Biliary excretion of lithocholate-3-O-glucuronide and lithocholate-3-sulfate in the Eisai hyperbilirubinuria rat was markedly delayed, whereas that of lithocholate was only slightly delayed. After [14C]chenodeoxycholate infusion (1 mumol/min/100 gm for 60 min), the increases in bile flow and biliary excretion of isotope in the Eisai hyperbilirubinuria rat were not so prominent as those observed in control rats, and the glucuronide of chenodeoxycholate, which constituted about 15% of biliary chenodeoxycholate in control rats, was not observed in the Eisai hyperbilirubinuria rat. Initial uptake of lithocholate and its glucuronide and sulfate by isolated hepatocytes was not impaired in the Eisai hyperbilirubinuria rat; the profiles of cytosolic bile acid binding proteins in Eisai hyperbilirubinuria rat liver were identical to those in control liver. These data indicate that the Eisai hyperbilirubinuria rat has excretory impairment of organic anions, bile acid glucuronide and sulfate and that it has characteristics very similar to those of the hyperbilirubinemic mutant Wistar rats TR- and GY.