tbuckley/cabot-search huggingface dataset:
International Prospective Study of Klebsiella pneumoniae Bacteremia: Implications of Extended-Spectrum β-Lactamase Production in Nosocomial Infections
Authors: David L. Paterson
Journal: Annals of Internal Medicine (2004)

Background: Commonly encountered nosocomially acquired gram-negative bacteria, especially Klebsiella pneumoniae, produce extended-spectrum β-lactamases (ESBLs) as an antibiotic resistance mechanism. Objective: To determine whether microbiology laboratories should report the presence of ESBLs and to establish the infection-control implications of ESBL-producing organisms. Design: Prospective observational study. Setting: 12 hospitals in South Africa, Taiwan, Australia, Argentina, the United States, Belgium, and Turkey. Patients: 440 patients with 455 consecutive episodes of K. pneumoniae bacteremia between 1 January 1996 and 31 December 1997; of these, 253 episodes were nosocomially acquired. Measurements: The K. pneumoniae isolates were examined for the presence of ESBLs. Pulsed-field gel electrophoresis was used to analyze the molecular epidemiology of nosocomial bacteremia with ESBL-producing K. pneumoniae. Results: Overall, 30.8% (78 of 253) episodes of nosocomial bacteremia and 43.5% (30 of 69) episodes acquired in intensive care units were due to ESBL-producing organisms. After adjustment for potentially confounding variables, previous administration of β-lactam antibiotics containing an oxyimino group (cefuroxime, cefotaxime, ceftriaxone, ceftazidime, or aztreonam) was associated with bacteremia due to ESBL-producing strains (risk ratio, 3.9 [95% CI, 1.1 to 13.8]). In 7 of 10 hospitals with more than 1 ESBL-producing isolate, multiple strains with the same genotypic pattern were observed, indicating patient-to-patient spread of the organism. Conclusions: Production of ESBLs by Klebsiella pneumoniae is a widespread nosocomial problem. Appropriate infection control and antibiotic management strategies are needed to stem the spread of this emerging form of resistance.
Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma
Authors: M. G. McCabe, L. M. Backlund, H. S. Leong, K. Ichimura, V. P. Collins
Journal: Neuro-Oncology (2011)

Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies.
A Requirement for Cyclin-Dependent Kinase 6 in Thymocyte Development and Tumorigenesis
Authors: Miaofen G. Hu, Amit Deshpande, Miriam Enos, Daqin Mao, Elisabeth A. Hinds, Guo-fu Hu, Rui Chang, Zhuyan Guo, Marei Dose, Changchuin Mao, Philip N. Tsichlis, Fotini Gounari, Philip W. Hinds
Journal: Cancer Research (2009)

Cyclin-dependent kinase 6 (CDK6) promotes cell cycle progression and is overexpressed in human lymphoid malignancies. To determine the role of CDK6 in development and tumorigenesis, we generated and analyzed knockout mice. Cdk6-deficient mice show pronounced thymic atrophy due to reduced proliferative fractions and concomitant transitional blocks in the double-negative stages. Using the OP9-DL1 system to deliver temporally controlled Notch receptor-dependent signaling, we show that CDK6 is required for Notch-dependent survival, proliferation, and differentiation. Furthermore, CDK6-deficient mice were resistant to lymphomagenesis induced by active Akt, a downstream target of Notch signaling. These results show a critical requirement for CDK6 in Notch/Akt-dependent T-cell development and tumorigenesis and strongly support CDK6 as a specific therapeutic target in human lymphoid malignancies.
Dose response in vivo to digoxin in normo- and hyperkalaemia: associated biochemical changes
Authors: R. H. GOLDMAN, D. J. COLTART, E. SCHWEIZER, G. SNIDOW, D. C. HARRISON
Journal: Cardiovascular Research (1975)

Journal Article Dose response in vivo to digoxin in normo- and hyperkalaemia: associated biochemical changes Get access ROBERT H. GOLDMAN, ROBERT H. GOLDMAN From The Cardiology Division, Stanford University School of Medicine, Stanford, California 94305, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar D. JOHN COLTART, D. JOHN COLTART 2 From The Cardiology Division, Stanford University School of Medicine, Stanford, California 94305, USA 2 Present address: St Thomas' Hospital, London SE1 7EN. Search for other works by this author on: Oxford Academic PubMed Google Scholar ESTHER SCHWEIZER, ESTHER SCHWEIZER From The Cardiology Division, Stanford University School of Medicine, Stanford, California 94305, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar GEORGE SNIDOW, GEORGE SNIDOW From The Cardiology Division, Stanford University School of Medicine, Stanford, California 94305, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar DONALD C. HARRISON DONALD C. HARRISON From The Cardiology Division, Stanford University School of Medicine, Stanford, California 94305, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 9, Issue 4, July 1975, Pages 515–523, https://doi.org/10.1093/cvr/9.4.515 Published: 01 July 1975
Humoral immunity to link protein in patients with inflammatory joint disease, osteoarthritis, and in non-arthritic controls.
Authors: A K Austin, R N Hobbs, J C Anderson, R C Butler, B A Ashton
Journal: Annals of the Rheumatic Diseases (1988)

Cartilage link protein of high purity was prepared and used in an enzyme linked immunosorbent assay (ELISA). Antibodies to link protein were sought in the sera of 98 patients with rheumatic disorders; 38 with rheumatoid arthritis (RA), 29 with osteoarthritis (OA), 13 with psoriatic arthritis (PA), nine with ankylosing spondylitis (AS), nine with systemic lupus erythematosus (SLE), and in 83 healthy controls. Antibodies were detected in all groups with the following prevalences: 21/83 normals, 9/38 RA, 7/29 OA, 7/13 PA, 3/9 AS, and 4/9 SLE. No statistically significant differences existed between the groups with regard to either prevalence or mean titre of anti-link antibodies. Serum antibodies to proteoglycan link protein appear to be no more common in patients with rheumatic disorders than in healthy controls.
The role of ultrasonography and automatic-needle biopsy in outpatient percutaneous liver biopsy
Authors: K D Lindor, C Bru, R A Jorgensen, J Rakela, J M Bordas, J B Gross, J Rodes, D B McGill, C C Reading, E M James, J W Charboneau, J Ludwig, K P Batts, A R Zinsmeister
Journal: Hepatology (1996)

The risk of complications from percutaneous liver biopsy is low, but discomfort is common and complications require hospitalization in approximately 4% of patients. The optimal method of performing these biopsies is unknown. The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle. Between 1992 and 1994, 836 patients were entered into a randomized study (489 in Rochester, MN; 347 in Barcelona, Spain). Patients were randomized immediately prior to liver biopsy into four groups: Trucut needle, or automatic biopsy needle, and with or without ultrasonography. Fisher’s Exact Test and a logistic regression model were also used to assess the effect of needle and ultrasonography on the odds for complications. The four biopsy groups were well-matched at entry with respect to age, sex, underlying liver disease, hemoglobin, prothrombin time, and platelet count. The use of ultrasound was associated with a decreased rate of hospitalization for pain, hypotension, or bleeding (2 vs. 9, P &lt; .05). No difference in safety was found between the two types of needles. The number of passes needed to obtain specimens was similar for all four groups. The average length of the specimen was slightly greater with ultrasonographic-guided biopsies (1.7 mm vs. 1.6 mm, P &lt; .05) and with biopsies obtained using the automatic biopsy needle when compared with the Trucut needle (1.7 mm vs. 1.5 mm, P &lt; .05), but this did not seem to be clinically important. The addition of ultrasonography reduces complications in patients undergoing percutaneous liver biopsy. The type of needle appears to offer little difference in safety or yield of diagnostic tissue. The use of ultrasonography for guidance of percutaneous liver biopsy will lead to a lower rate of complications. The value of this benefit must be weighed against the added cost of ultrasonographic guidance.
Disruption of the <i>Cathepsin K</i> Gene Reduces Atherosclerosis Progression and Induces Plaque Fibrosis but Accelerates Macrophage Foam Cell Formation
Authors: E. Lutgens, S.P.M. Lutgens, B.C.G. Faber, S. Heeneman, M.M.J. Gijbels, M.P.J. de Winther, P. Frederik, I. van der Made, A. Daugherty, A.M. Sijbers, A. Fisher, C.J. Long, P. Saftig, D. Black, M.J.A.P. Daemen, K.B.J.M. Cleutjens
Journal: Circulation (2005)

Background— Cathepsin K (catK), a lysosomal cysteine protease, was identified in a gene-profiling experiment that compared human early plaques, advanced stable plaques, and advanced atherosclerotic plaques containing a thrombus, where it was highly upregulated in advanced stable plaques. Methods and Results— To assess the function of catK in atherosclerosis, catK −/− /apolipoprotein (apo) E −/− mice were generated. At 26 weeks of age, plaque area in the catK −/− /apoE −/− mice was reduced (41.8%) owing to a decrease in the number of advanced lesions as well as a decrease in individual advanced plaque area. This suggests an important role for catK in atherosclerosis progression. Advanced plaques of catK −/− /apoE −/− mice showed an increase in collagen content. Medial elastin fibers were less prone to rupture than those of apoE −/− mice. Although the relative macrophage content did not differ, individual macrophage size increased. In vitro studies of bone marrow derived–macrophages confirmed this observation. Scavenger receptor–mediated uptake (particularly by CD36) of modified LDL increased in the absence of catK, resulting in an increased macrophage size because of increased cellular storage of cholesterol esters, thereby enlarging the lysosomes. Conclusions— A deficiency of catK reduces plaque progression and induces plaque fibrosis but aggravates macrophage foam cell formation in atherosclerosis.
Antitumor Effects and Biomarkers of Activity of AZD0530, a Src Inhibitor, in Pancreatic Cancer
Authors: N.V. Rajeshkumar, Aik Choon Tan, Elizabeth De Oliveira, Chris Womack, Helen Wombwell, Shethah Morgan, Madhuri V. Warren, Jill Walker, Tim P. Green, Antonio Jimeno, Wells A. Messersmith, Manuel Hidalgo
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To determine the efficacy of AZD0530, an orally active small molecule Src inhibitor, in human pancreatic cancer xenografts and to seek biomarkers predictive of activity. Experimental Design: Sixteen patient-derived pancreatic cancer xenografts from the PancXenoBank collection at Johns Hopkins were treated with AZD0530 (50 mg/kg/day, p.o.) for 28 days. Baseline gene expression profiles of differently expressed genes in 16 tumors by Affymetrix U133 Plus 2.0 gene array were used to predict AZD0530 sensitivity in an independent group of eight tumors using the K-Top Scoring Pairs (K-TSP) method. Results: Three patient tumors of 16 were found to be sensitive to AZD0530, defined as tumor growth &amp;lt;50% compared with control tumors (100%). Western blot and/or immunohistochemistry results showed that AZD0530 administration resulted in the down-regulation of Src, FAK, p-FAK, p-paxillin, p-STAT-3, and XIAP in sensitive tumor xenografts compared with control tumors. The K-TSP classifier identified one gene pair (LRRC19 and IGFBP2) from the 16 training cases based on a decision rule. The classifier achieved 100% and 83.3% of sensitivity and specificity in an independent test set that consists of eight xenograft cases. Conclusions: AZD0530 treatment significantly inhibits the tumor growth in a subset of human pancreatic tumor xenografts. One gene pair (LRRC19 and IGFBP2) identified by the K-TSP classifier has high predictive power for AZD0530 sensitivity, suggesting the potential for this gene pair as biomarker for pancreatic tumor sensitivity to AZD0530.
Enhanced Inhibition of ERK Signaling by a Novel Allosteric MEK Inhibitor, CH5126766, That Suppresses Feedback Reactivation of RAF Activity
Authors: Nobuya Ishii, Naoki Harada, Eric W. Joseph, Kazuhiro Ohara, Takaaki Miura, Hiroshi Sakamoto, Yutaka Matsuda, Yasushi Tomii, Yukako Tachibana-Kondo, Hitoshi Iikura, Toshihiro Aoki, Nobuo Shimma, Mikio Arisawa, Yoshihiro Sowa, Poulikos I. Poulikakos, Neal Rosen, Yuko Aoki, Toshiyuki Sakai
Journal: Cancer Research (2013)

Tumors with mutant RAS are often dependent on extracellular signal-regulated kinase (ERK) signaling for growth; however, MEK inhibitors have only marginal antitumor activity in these tumors. MEK inhibitors relieve ERK-dependent feedback inhibition of RAF and cause induction of MEK phosphorylation. We have now identified a MEK inhibitor, CH5126766 (RO5126766), that has the unique property of inhibiting RAF kinase as well. CH5126766 binding causes MEK to adopt a conformation in which it cannot be phosphorylated by and released from RAF. This results in formation of a stable MEK/RAF complex and inhibition of RAF kinase. Consistent with this mechanism, this drug does not induce MEK phosphorylation. CH5126766 inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity as well. These results suggest that relief of RAF feedback limits pathway inhibition by standard MEK inhibitors. CH5126766 represents a new type of MEK inhibitor that causes MEK to become a dominant-negative inhibitor of RAF and that, in doing so, may have enhanced therapeutic activity in ERK-dependent tumors with mutant RAS.
2-D ULTRASOUND SPECKLE TRACKING STRAIN IMAGING OF THE LEFT ATRIUM IN THE ESTIMATION OF LEFT VENTRICULAR FILLING PRESSURES.
Authors: Mitsuru Masaki, Yong-Mei Cha, Toshinori Yuasa, Gabriella Veress, Kan Dong, Ying-Xue Dong, Sunil V. Mankad, Jae K. Oh
Journal: Journal of the American College of Cardiology (2010)
Novel action of gastric proton pump inhibitor on suppression of Helicobacter pylori induced angiogenesis
Authors: M Yeo
Journal: Gut (2005)

<b>Background:</b> Although activation of mitogen activated protein kinases (MAPKs) by <i>Helicobacter pylori</i> infection is associated with induction of host angiogenesis, which may contribute to <i>H pylori</i> associated gastric carcinogenesis, the strategy for its prevention has not been identified. As we previously reported a strong inhibitory action of gastric proton pump inhibitors (PPIs) on MAPK extracellular signal regulated kinase (ERK)1/2 phosphorylation, we investigated whether PPIs could suppress the <i>H pylori</i> induced angiogenesis via inhibition of MAPK ERK1/2. <b>Methods:</b> To address the relationship between <i>H pylori</i> infection and angiogenesis, comparative analysis of density of CD34<sup>+</sup> blood vessel was performed in tissues obtained from 20 <i>H pylori</i> positive gastritis and 18 <i>H pylori</i> negative gastritis patients. Expression of hypoxia inducible factor 1 (HIF-1α) and vascular endothelial growth factor (VEGF) was tested by reverse transcription-polymerase chain reaction and secretion of interleukin 8, and VEGF was measured by ELISA. To evaluate the direct effect of <i>H pylori</i> infection on the tubular formation of human umbilical vein endothelial cells (HUVEC), an in vitro angiogenesis assay was employed. Activation of MAPK and nuclear factor κB (NFκB) was detected by immunoblotting. <b>Results:</b><i>H pylori</i> positive gastritis patients showed a higher density of CD34<sup>+</sup> blood vessels (mean 40.9 (SEM 4.4)) than <i>H pylori</i> negative gastritis patients (7.2±0.8), which was well correlated with expression of HIF-1α. Conditioned media from <i>H pylori</i> infected gastric epithelial cells directly induced tubular formation of HUVEC and the increase of in vitro angiogenesis was suppressed by PPI treatment. Infection of <i>H pylori</i> significantly upregulated expression of HIF-1α and VEGF in gastric epithelial cells and expression of proangiogenic factors was mediated by MAPK activation and partially responsible for NFκB activation. PPIs effectively inhibited the phosphorylation of MAPK ERK1/2 that is a principal signal for <i>H pylori</i> induced angiogenesis. <b>Conclusions:</b> The fact that PPIs could downregulate <i>H pylori</i> induced angiogenesis indicates that antiangiogenic treatment using a PPI could be a promising protective therapeutic approach for <i>H pylori</i> associated carcinogenesis.
Homeostasis and drinking
Authors: F. M. Toates
Journal: Behavioral and Brain Sciences (1979)

Abstract Drinking and thirst-motivated behaviour have traditionally been explained in terms of the rather simple concept of homeostasis. A homeostatic mechanism readily accounts for responses to acute changes in body-fluid levels. However, there are other factors regulating intake, for example, cues associated with eating, which interact with the time elapsed since last drinking and the availability of water. Future dehydration is avoided by behavioural hysteresis; a sudden reduction in fluid needs is not matched by an equivalent reduction in fluid intake. Another factor not explicable by traditional homeostasis is that, in general, drinking cannot be suppressed by water infusion. Nor are there rigid target values for body-fluid levels independent of the cost of obtaining water; when water is hard to get, a relatively low body fluid level is maintained, thus minimizing loss. On the basis of the results conflicting with traditional homeostatic theory, this paper tentatively suggests certain modifications toward a more realistic model of fluid ingestion.
T cell receptor-independent CD2 signal transduction in FcR+ cells.
Authors: A R Arulanandam, S Koyasu, E L Reinherz
Journal: The Journal of Experimental Medicine (1991)

CD2 subserves both adhesion and signal transduction functions in T cells, thymocytes, and natural killer (NK) cells. In mature T lymphocytes, CD2-mediated signaling function apparently requires surface expression of T cell receptors (TCRs). In contrast, in CD2+ CD3- NK cells and thymocytes, signal transduction through CD2 is TCR independent. To resolve this paradox and characterize TCR-independent triggering mechanisms, we transfected a human CD2 cDNA into a murine mast cell line, C1.MC/57 (Fc epsilon RI+, Fc gamma RII+, Fc gamma RIII+), which is known to produce interleukin 6 (IL-6) as well as release histamine in response to crosslinking of Fc epsilon RI. In the CD2 transfectant, a combination of anti-T11(2) + anti-T11(3) monoclonal antibodies (mAbs) induced a rise in intracellular free calcium [( Ca2+]i), IL-6 production, and histamine release. As expected, no activation was mediated by the same mAbs in C1.MC/57. F(ab)'s fragments of the activatory combination of anti-T11(2) + anti-T11(3) mAbs induced IL-6 in the CD2-transfected mast cells, demonstrating an Fc gamma receptor ectodomain-independent triggering mechanism. In addition, either intact anti-T11(2) or anti-T11(3) IgG alone, which failed to induce [Ca2+]i mobilization in the transfectant, was able to induce IL-6 production. A mAb directed against both Fc gamma RII (previously denoted as Fc gamma RIIb) and Fc gamma RIII (previously denoted as Fc gamma RIIa) inhibits this induction. These results indicate that: (a) Ca2+ mobilization is not essential for IL-6 production; and (b) crosslinking of CD2 and Fc gamma receptors via intact anti-CD2 IgG stimulates IL-6 production. Thus, CD2-mediated IL-6 production occurs by both Fc receptor ectodomain-independent as well as Fc receptor ectodomain-dependent mechanisms in these nonlymphoid cells. Northern blot analysis demonstrates that although the mast cells do not express CD3 zeta or CD3 eta mRNA, they express Fc epsilon RI gamma mRNA. The latter is a known component of Fc gamma RIII as well as Fc epsilon RI, has significant homology to CD3 zeta/eta, and is thought to have a signal transduction function. In these mast cells, CD2 signaling machinery does not require CD3 zeta/eta and may be linked to the Fc epsilon RI gamma subunit. We predict that this subunit or a related structure may confer a TCR-independent signal transduction pathway upon CD2 in CD3- NK cells, thymocytes, and certain B lymphocytes.
Automatic classification of pulmonary peri-fissural nodules in computed tomography using an ensemble of 2D views and a convolutional neural network out-of-the-box
Authors: Francesco Ciompi, Bartjan de Hoop, Sarah J. van Riel, Kaman Chung, Ernst Th. Scholten, Matthijs Oudkerk, Pim A. de Jong, Mathias Prokop, Bram van Ginneken
Journal: Medical Image Analysis (2015)
Characterization of within-subject responses to fluticasone and montelukast in childhood asthma
Authors: Stanley J. Szefler, Brenda R. Phillips, Fernando D. Martinez, Vernon M. Chinchilli, Robert F. Lemanske, Robert C. Strunk, Robert S. Zeiger, Gary Larsen, Joseph D. Spahn, Leonard B. Bacharier, Gordon R. Bloomberg, Theresa W. Guilbert, Gregory Heldt, Wayne J. Morgan, Mark H. Moss, Christine A. Sorkness, Lynn M. Taussig
Journal: Journal of Allergy and Clinical Immunology (2005)