tbuckley/cabot-search huggingface dataset:
Distinct Changes of Genomic Biases in Nucleotide Substitution at the Time of Mammalian Radiation
Authors: P. F. Arndt
Journal: Molecular Biology and Evolution (2003)

Differences in the regional substitution patterns in the human genome created patterns of large-scale variation of base composition known as genomic isochores.To gain insight into the origin of the genomic isochores we develop a maximum likelihood approach to determine the history of substitution patterns in the human genome.This approach utilizes the vast amount of repetitive sequence deposited in the human genome over the past ~250 MYR.Using this approach we estimate the frequencies of seven types of substitutions: the four transversions, two transitions, and the methyl-assisted transition of cytosine in CpG.Comparing substitutional patterns in repetitive elements of various ages, we reconstruct the history of the base-substitutional process in the different isochores for the past 250 Myr.At around 90 Myr ago (around the time of the mammalian radiation), we find an abrupt 4-to 8-fold increase of the cytosine transition rate in CpG pairs compared to that of the reptilian ancestor.Further analysis of nucleotide substitutions in regions with different GC-content reveals concurrent changes in the substitutional patterns.While the substitutional pattern was dependent on the regional GC-content in such ways that it preserved the regional GC-content before the mammalian radiation, it lost this dependence afterwards.The substitutional pattern changed from an isochorepreserving to an isochore-degrading one.We conclude that isochores have been established before the radiation of the eutherian mammals and have been subject to the process of homogenization since then.
Neonatal Hyperoxia Enhances the Inflammatory Response in Adult Mice Infected with Influenza A Virus
Authors: Michael A. O'Reilly, Shauna H. Marr, Min Yee, Sharon A. McGrath-Morrow, B. Paige Lawrence
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Lungs of adult mice exposed to hyperoxia as newborns are simplified and exhibit reduced function much like that observed in people who had bronchopulmonary dysplasia (BPD) as infants. Because survivors of BPD also show increased risk for symptomatic respiratory infections, we investigated how neonatal hyperoxia affected the response of adult mice infected with influenza A virus infection.To determine whether neonatal hyperoxia increased the severity of influenza A virus infection in adult mice.Adult female mice exposed to room air or hyperoxia between Postnatal Days 1 and 4 were infected with a sublethal dose of influenza A virus.The number of macrophages, neutrophils, and lymphocytes observed in airways of infected mice that had been exposed to hyperoxia as neonates was significantly greater than in infected siblings that had been exposed to room air. Enhanced inflammation correlated with increased levels of monocyte chemotactic protein-1 (CCL2) in lavage fluid, whereas infection-associated changes in IFN-gamma, IL-1beta, IL-6, tumor necrosis factor-alpha, KC, granulocyte-macrophage colony-stimulating factor, and macrophage inflammatory protein-1alpha, and production of virus-specific antibodies, were largely unaffected. Increased mortality of mice exposed to neonatal hyperoxia occurred by Day 14 of infection, and was associated with persistent inflammation and fibrosis.These data suggest that the disruptive effect of hyperoxia on neonatal lung development also reprograms key innate immunoregulatory pathways in the lung, which may contribute to exacerbated pathology and poorer resistance to respiratory viral infections typically seen in people who had BPD.
Climate Variability and Hemorrhagic Fever with Renal Syndrome Transmission in Northeastern China
Authors: Wen-Yi Zhang, Wei-Dong Guo, Li-Qun Fang, Chang-Ping Li, Peng Bi, Gregory E. Glass, Jia-Fu Jiang, Shan-Hua Sun, Quan Qian, Wei Liu, Lei Yan, Hong Yang, Shi-Lu Tong, Wu-Chun Cao
Journal: Environmental Health Perspectives (2010)

The transmission of hemorrhagic fever with renal syndrome (HFRS) is influenced by climatic variables. However, few studies have examined the quantitative relationship between climate variation and HFRS transmission.We examined the potential impact of climate variability on HFRS transmission and developed climate-based forecasting models for HFRS in northeastern China.We obtained data on monthly counts of reported HFRS cases in Elunchun and Molidawahaner counties for 1997-2007 from the Inner Mongolia Center for Disease Control and Prevention and climate data from the Chinese Bureau of Meteorology. Cross-correlations assessed crude associations between climate variables, including rainfall, land surface temperature (LST), relative humidity (RH), and the multivariate El Niño Southern Oscillation (ENSO) index (MEI) and monthly HFRS cases over a range of lags. We used time-series Poisson regression models to examine the independent contribution of climatic variables to HFRS transmission.Cross-correlation analyses showed that rainfall, LST, RH, and MEI were significantly associated with monthly HFRS cases with lags of 3-5 months in both study areas. The results of Poisson regression indicated that after controlling for the autocorrelation, seasonality, and long-term trend, rainfall, LST, RH, and MEI with lags of 3-5 months were associated with HFRS in both study areas. The final model had good accuracy in forecasting the occurrence of HFRS.Climate variability plays a significant role in HFRS transmission in northeastern China. The model developed in this study has implications for HFRS control and prevention.
Chemotherapy of bronchitis.
Authors: D Hansman, M Pidgeon
Journal: BMJ (1971)

uncomplicated viral hepatitis patients with a high E.S.R. are likely to be of the short incubation period type.Giles and her colleagues6 found that in about one-third of their patients the anti- gen could only be demonstrated during the incubation period, so that it is possible that patients with a low E.S.R. who are antigennegative by the double-diffusion test may be of the long incubation period type.Further investigation is necessary, using more sen- sitive tests, to show whether this is so.Krugman et al. found that the thymol tur- bidity test was usually normal in the long incubation period type and high in the short incubation period type.'These findings, and those of the E.S.R., could be explained by changes in the serum proteins.Most laboratories are unable to do the simple double-diffusion test because of the scarcity of the specific antibody.The E.S.R. can be done in all types of hospital and it is hoped that may prove an additional help in the differentiation of the two types of viral hepatitis.-Iam, etc.,
Tumor necrosis factor increases mitochondrial oxidant production and induces expression of uncoupling protein-2 in the regenerating rat liver
Authors: Janet F.Y. Lee, Yunbo Li, Hong Zhu, ShiQi Yang, Hui Zhi Lin, Michael Trush, Anna Mae Diehl
Journal: Hepatology (1999)

The growth-stimulatory actions of tumor necrosis factor alpha (TNF-alpha) after partial hepatectomy (PH) are difficult to reconcile with its well-established role in the genesis of liver injury. The lethal actions of TNF are thought to involve the induction of oxidant production by mitochondria. It is not known if TNF initiates mitochondrial oxidant production after PH. Furthermore, if this potentially toxic response follows PH, it is not clear how hepatocytes defend themselves sufficiently so that replication, rather than death, occurs. These studies test the hypothesis that TNF does increase mitochondrial oxidant production after PH but that these oxidants primarily promote the induction of antioxidant defenses in regenerating hepatocytes. Consistent with this concept, H2O2 production by liver mitochondria increases from 5 minutes to 3 hours after PH, beginning before the transient inductions of hepatic NF kB activity (which peaks at 30 minutes post-PH) and uncoupling protein-2 (UCP-2) (which begins around 30 minutes and peaks from 6-24 hours post-PH). Pretreatment with neutralizing anti-TNF antibodies, which inhibits hepatocyte DNA synthesis after PH, also reduces post-PH hepatic mitochondrial oxidant production by 80% and inhibits NF kappaB activation and UCP-2 induction by 50% and 80%, respectively. In contrast, pretreatment with D609, an agent that inhibits phosphatidylcholine-specific phospholipase C, neither inhibits regenerative induction of mitochondrial oxidant production, UCP-2 expression, nor hepatocyte DNA synthesis, although it inhibits NF kappaB activation by 50%. Given published evidence that NF kappaB is antiapoptotic and that UCP-2 may decrease mitochondrial oxidant production in some cells, these results suggest that TNF-dependent increases in oxidant production by liver mitochondria promote the induction of antioxidant defenses in the regenerating liver.
A genome-wide association study of bronchodilator response in Latinos implicates rare variants
Authors: Katherine A. Drake, Dara G. Torgerson, Christopher R. Gignoux, Joshua M. Galanter, Lindsey A. Roth, Scott Huntsman, Celeste Eng, Sam S. Oh, Sook Wah Yee, Lawrence Lin, Carlos D. Bustamante, Andrés Moreno-Estrada, Karla Sandoval, Adam Davis, Luisa N. Borrell, Harold J. Farber, Rajesh Kumar, Pedro C. Avila, Emerita Brigino-Buenaventura, Rocio Chapela, Jean G. Ford, Michael A. LeNoir, Fred Lurmann, Kelley Meade, Denise Serebrisky, Shannon Thyne, William Rodríguez-Cintrón, Saunak Sen, José R. Rodríguez-Santana, Ryan D. Hernandez, Kathleen M. Giacomini, Esteban G. Burchard
Journal: Journal of Allergy and Clinical Immunology (2013)
Electrocardiographic effects of dexmedetomidine in patients with congenital heart disease
Authors: Constantinos Chrysostomou, Rukmini Komarlu, Steven Lichtenstein, Dana Shiderly, Gaurav Arora, Richard Orr, Peter D. Wearden, Victor O. Morell, Ricardo Munoz, Edmund H. Jooste
Journal: Intensive Care Medicine (2010)
374 EXPRESSION OF THE NUCLEAR FACTOR KAPPA B (NFKB) P50/P65 PROTEINS IN HEPATOCELLULAR CARCINOMA (HCC): LACK OF PREDICTIVE VALUE FOR RESPONSE TO THALIDOMIDE TREATMENT
Authors: C. Hsu, L.T. Chen, Y. Chao, H.H. Fan, Y.C. Shen, A.L. Cheng
Journal: Journal of Hepatology (2008)
Increased prooxidant action of hepatic cytosolic low-molecular-weight iron in experimental iron overload
Authors: Robert S. Britton, Marco Ferrali, Christopher J. Magiera, Richard O. Recknagel, Bruce R. Bacon
Journal: Hepatology (1990)

In the iron-loaded liver there may be an increase in the putative intracellular transit pool of iron, components of which could be catalytically active in stimulating lipid peroxidation. To study the levels of low-molecular-weight, catalytically active iron in the liver, cytosolic ultrafiltrates were tested in an assay containing rat liver microsomes and NADPH. Malondialdehyde production was used as an index of lipid peroxidation. This assay system was sensitive enough to detect 0.25 mumol/L ferrous iron; progressive but non-linear increases in malondialdehyde were produced as the iron concentration was increased to 5 mumol/L. Ultrafiltrates from hepatic cytosol of iron-loaded rats had greater prooxidant action than did those from controls. When added to the assay, deferoxamine, an iron chelator, completely suppressed the prooxidant action of hepatic ultrafiltrates, showing that this activity is iron-dependent. Deferoxamine administered intraperitoneally to control animals at a dose of 1 gm/kg completely inhibited the prooxidant effect of hepatic ultrafiltrates prepared from rats killed after 1, 2 and 3 hr. Partial inhibition was observed at 4 hr; by 6 hr the inhibitory effect of deferoxamine was completely lost. Administration of deferoxamine (1 gm/kg intraperitoneally, 1 hr before killing) completely inhibited the prooxidant action of hepatic ultrafiltrates in moderately iron-loaded rats and controls but had no protective effect in heavily iron-loaded rats. These results support the concept that iron overload results in an increase in a hepatic cytosolic pool of low-molecular-weight iron that is catalytically active in stimulating lipid peroxidation. This pool can be chelated transiently in vivo by deferoxamine in moderate, but not heavy, iron overload.
Phase 2 Early Afterdepolarization as a Trigger of Polymorphic Ventricular Tachycardia in Acquired Long-QT Syndrome
Authors: Gan-Xin Yan, Ying Wu, Tengxian Liu, Jixin Wang, Roger A. Marinchak, Peter R. Kowey
Journal: Circulation (2001)

Background —This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl -sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. Methods and Results —Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl -Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 μmol/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 μmol/L but shortened them at 30 μmol/L. Unlike dl -sotalol, azimilide (&gt;3 μmol/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl -sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl -sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 μmol/L) increased APD more than dl -sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. Conclusions —This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation.
EVALUATION OF THE CAPILLARY RESISTANCE TEST IN THE DIAGNOSIS OF SUBCLINICAL SCURVY
Authors: DAVID GREENE
Journal: JAMA (1934)

In the field of nutrition there have been evolved methods for the determination of deficiencies of the various vitamins in the diet. These methods, now definitely established, apply to both manifest and latent avitaminosis. The search is still continuing for finer methods which will detect the earliest manifestations— even before clinical signs become evident. In this connection there have recently appeared a number of papers concerning the antiscorbutic vitamin C. Hess<sup>1</sup>in 1914 demonstrated, by means of the blood pressure tourniquet, the increased fragility of the blood capillaries in manifest scurvy as evidenced by the development of petechial spots along the forearm. He found that the test was positive in the majority of cases of this disease, indicating a weakness of the capillary vessel walls due to a failure on the part of the endothelial cells to form cement substance. In 1928 Öhnell,<sup>2</sup>too, established the value of
Correct determination of critical flicker frequency is mandatory when comparisons to other tests are made
Authors: Gerald Kircheis, Norbert Hilger, Dieter Häussinger
Journal: Gut (2013)

A bleeding disorder occurring during labour and affecting mother and foetus is described. All stages of coagulation were normal until the reaction fibrinogen→fibrin. Either there was some abnormality present in the fibrinogen molecule, or there was an “anticoagulant” acting at this stage. The abnormality was reversible by protamine sulphate and toluidine blue, but in other respects did not resemble hyperheparinaemia. Reversibility of a clotting defect by protamine or toluidine blue is not sufficient evidence on which to make a diagnosis of hyperheparinaemia. Demonstration of a prolonged clotting time occurring in late pregnancy does not necessarily justify the diagnosis of “afibrinogenaemia.”
Abstract 2742: Identification of tumor antigens in neu transgenic mice may provide biomarkers useful for the early detection and diagnosis of human breast cancer
Authors: Mei Wu, Edmond Marzbani, Jianning Mao, Mariam Shehata, Rachel Y. J. Kim, Hailing Lu, Mary L. Disis
Journal: Cancer Research (2010)

Abstract Early detection of breast cancer is crucial for better prognosis and successful treatment of the patients. Development of novel methods for screening for breast cancer is needed for early detection and diagnosis. The human immune system responds to tumor-specific antigens in the pre-malignant stage of breast cancer and produces specific antibodies, which can be detected as potential breast cancer biomarkers. Due to the limited availability of well-annotated pre-cancer and post-cancer sera from human subjects, we performed serial serum collection in a neu transgenic mouse model from the age of 10 weeks to the terminal stage of disease. Using a technique called serological screening of cDNA expression library (SEREX), a high-throughput method to rapidly screen recombinant proteins expressed in a bacteriophage-based cDNA library, we have previously identified tumor antigens in the late stage of neu breast cancers. The mouse tumors have similar immunogenicity as their human counterparts due to the fact that some of these antigens are also immunogenic in human. Indeed, we have found that one mouse antigen called gelsolin, shares 93% homology with human gelsolin and has the highest response to human serum antibody among other antigens. In an ELISA analysis using the serum samples from 50 breast cancer cases and 50 normal donors, the area-under-curve (AUC) value of the receiver-operating-characteristic (ROC) curve of gelsolin ELISA detects more than 70% of cancer patients. Using the SEREX technique, we sought to further identify the early-stage serum antibody biomarkers by comparing the pre-cancer, early stage, and late stage sera from the same mouse. We have identified three early-stage biomarkers, A20/TNFaip3, Rpl5, and Pdhx, in neu mice. In summary, we conclude that identification of tumor antigens in the neu transgenic animal model is useful for the discovery of serum antibody biomarkers for early detection and diagnosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2742.
Viability of fresh mitral homograft valves
Authors: N. Al-Janabi, D. N. Ross
Journal: Thorax (1973)

The present study was undertaken to measure and compare the viability of the mitral leaflet, chordae, and papillary muscle. The viability of the valves was assessed by autoradiography at regular intervals after sterilization and preservation in antibiotics and nutrient medium. The results showed different rates of decline in viability of the leaflet, muscle, and chordae of the mitral valves. Slightly more than 70% of the leaflet fibroblasts took up thymidine during the first 24 hours of storage. This is compared with 68% of papillary muscle fibroblasts and 40% of chordae fibroblasts. Viability of the chordae decreased rapidly and became pronounced at four weeks. One week is the maximum time for storage of mitral valves if it is desirable to preserve living cells in the chordae.
A dramatic, objective antiandrogen withdrawal response: case report and review of the literature
Authors: Yiu-Keung Lau, Manpreet K Chadha, Alan Litwin, Donald L Trump
Journal: Journal of Hematology & Oncology (2008)

Abstract Antiandrogen withdrawal response is an increasingly recognized entity in patients with metastatic prostate cancer. To our knowledge, there have been no reports describing a durable radiologic improvement along with prostate-specific antigen (PSA) with discontinuation of the antiandrogen agent bicalutamide. We report a case in which a dramatic decline of serum PSA levels associated with a dramatic improvement in radiologic disease was achieved with bicalutamide discontinuation.
Endarterectomy in Carotid Artery Disease-Reply
Authors: Stephen G. Pauker
Journal: JAMA (1987)

<h3>In Reply.—</h3> Although Dr Rolak believes that carotid surgery has no efficacy in preventing cerebral ischemic events, not all of his colleagues would agree. Many physicians believe that the procedure can be useful, even lifesaving, in certain patients or subsets of patients. They might argue that the overall series reported in the literature can mask the benefit in specific patients. The model we developed attempts to focus this debate by replacing emotional tirades by measured logic. Through sensitivity analysis, we asked under what circumstances would carotid endarterectomy offer any benefit, and what would the magnitude of that benefit be. We identified three factors that are central to this judgment: (1) the rate of operative complications, (2) the rate of ischemic events without surgery, and (3) the efficacy of surgery in the specific clinical circumstance. By focusing on these variables, we hoped to enhance the quality of the scientific debate and
Functional significance of endothelin B receptors in mediating sinusoidal and extrasinusoidal effects of endothelins in the intact rat liver
Authors: Michael Bauer, Inge Bauer, Natalie V. Sonin, Nicole Kresge, Rajiv Baveja, Yukihiro Yokoyama, David Harding, Jian X. Zhang, Mark G. Clemens
Journal: Hepatology (2000)

Endothelins (ET) are important regulators of the hepatic microcirculation that act through different receptor subtypes. We investigated functional significance of ET B receptors in mediating microhemodynamic effects of ETs in normal and endotoxin (lipopolysaccharide [LPS])-primed rat liver. LPS priming ( Escherichia coli O26:B6; 1 mg · kg −1 ) selectively increased ET B mRNA and led to a shift in available receptors to the ET B subtype. IRL 1620 (an ET B agonist) increased portal pressure in a dose-dependent manner, and the increase in ET B expression was associated with prolonged portal pressor response in isolated livers. However, lactate dehydrogenase (LDH) release was attenuated and sinusoidal blood flow was better maintained upon ET B stimulation in vivo . In isolated livers, portal constriction as well as release of LDH, were substantially increased in the presence of N ω -nitro-l-arginine methyl ester (l-NAME), an inhibitor of nitric oxide synthase (NOS). In vivo microscopic assessment of sinusoidal perfusion during ET B stimulation revealed a disruption of the flow pattern including frequent reversal of the flow direction without significant sinusoid constriction. Sinusoidal flow decreased even further after discontinuation of IRL 1620. Both effects were mediated at extrasinusoidal sites that probably included postsinusoidal sites. However, after pretreatment with l-NAME, IRL 1620 evoked a significant sinusoidal constriction that colocalized with the body of the stellate cell. We propose that ET B1 -induced NOS activity attenuates ET B2 (and presumably ET A )-mediated portal pressor response and stellate cell constriction. Transcriptional activation of the ET B gene may have a permissive effect on liver blood flow and protect against hepatocellular damage under pathophysiological conditions associated with endotoxemia.
Magnetic resonance imaging is to be exempt from European rules restricting use of electromagnetic fields
Authors: R. Watson
Journal: BMJ (2011)

Magnetic resonance imaging (MRI) used for medical diagnosis and treatment will be exempt from new Europe-wide rules designed to protect workers from electromagnetic fields. The decision comes after a four year campaign by radiologists, scientists, and patients’ groups who feared that the legislation would severely restrict use of the technology.

Mary Baker, president of the European Brain Council, said, “This proposal ensures that patients across Europe will be able to receive the highest standard of care and will not be forced into the …