tbuckley/cabot-search huggingface dataset:
Histone Deacetylase Inhibitor Romidepsin Has Differential Activity in Core Binding Factor Acute Myeloid Leukemia
Authors: Olatoyosi M. Odenike, Serhan Alkan, Dorie Sher, John E. Godwin, Dezheng Huo, Stephen J. Brandt, Margaret Green, Jingping Xie, Yanming Zhang, David H. Vesole, Patrick Stiff, John Wright, Richard A. Larson, Wendy Stock
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Recruitment of histone deacetylases (HDAC) is a mechanism of transcriptional repression implicated in the differentiation block in acute myeloid leukemia (AML). We hypothesized that the HDAC inhibitor romidepsin could cause transcriptional derepression, up-regulation of specific target genes in AML, and differentiation of the leukemic clone. The primary objectives of the study were to evaluate the safety and efficacy of romidepsin in advanced AML. Experimental Design: Twenty patients were stratified into cohort A or B based on the absence or presence of chromosomal abnormalities known to recruit HDACs, including those involving core binding factor (CBF). Romidepsin was administered i.v. at 13 mg/m2/d on days 1, 8, and 15 of a 28-day cycle. Pharmacodynamic endpoints were evaluated at serial time points. Results: Common adverse effects noted were grade 1 to 2 nausea, anorexia, and fatigue. No objective evidence of antileukemic activity was seen in cohort A. In cohort B, although there were no clinical responses by standard criteria, antileukemic activity was observed in 5 of 7 patients. Two patients had clearance of bone marrow blasts and 3 patients had a &amp;gt;50% decrease in bone marrow blasts. Furthermore, in cohort B, at 24 h, there was a significant increase in MDR1 (P = 0.005), p15 (P = 0.01), and p14 (P &amp;lt; 0.0001) expression. In cohort A, although there was a trend toward up-regulation of MDR1, p15, and p14 expression, these changes were not statistically significant. Conclusion: Romidepsin has differential antileukemic and molecular activity in CBF AML. Development of this agent in CBF AML should focus on combinations that target related mechanisms of gene silencing such as DNA methylation.
Is Helicobacter pylori antibiotic resistance surveillance needed and how can it be delivered? a feasibility study in three centres
Authors: G. Lasseter, S. D'Arcy, A. Lawson, I. Shaw, E. Glocker, C. A. M. Mcnulty
Journal: Gut (2011)

<h3>Introduction</h3> <i>Helicobacter pylori</i> eradication requires PPI with two antibiotics: amoxicillin, clarithromycin or metronidazole. Treatment failures are increasing and alternative antibiotics include tetracyclines, quinolones and rifabutin. In England in 2008 <i>H. pylori</i> culture and antibiotic sensitivity was only routinely performed in Gloucester and the Helicobacter Reference Unit (HRU). <h3>Methods</h3> Determine the feasibility of <i>H. pylori</i> antimicrobial resistance surveillance, using gastric antral biopsy specimens from routine endoscopies cultured in Gloucester and Bangor and referred to HRU. European standard methods were used for culture and susceptibility by E-tests. <h3>Results</h3> Prevalence was low: Bangor 6.6%, Gloucester 5.5% and HRU 32.2%. Higher resistance rates in the HRU reflected a greater proportion of referrals ‘post treatment’. Resistance rates were: Metronidazole, HRU 87%, Glos 22%, Bangor 38%; Clarithromycin, HRU 68%, Glos 4%, Bangor 15%; Levofloxacin, HRU 17%, Glos 1%, Bangor 13%; Rifabutin, HRU 0%, Glos 2.8%, Bangor 3.3%; Amoxicillin, HRU 2.8%, Glos 0%, Bangor 1.7%; Tetracycline HRU &lt;1%, Glos 1.4%, Bangor 0%. Patient history was collected retrospectively for all samples and despite paying endoscopy staff, data collection was poor. Consequently a dedicated staff member in Gloucester PCU completed all data collection. <h3>Conclusion</h3> Surveillance is essential as a primary Clarithromycin resistance varies greatly between centres. There is higher resistance post treatment. In future a dedicated clerical officer will be required to collect all data. As prevalence is low, large numbers of biopsy specimens are needed to attain sufficient numbers of culture isolates for antibiotic susceptibility surveillance areas of higher prevalence.
American football injuries in Finland.
Authors: J Karpakka
Journal: British Journal of Sports Medicine (1993)

American football is currently played in 14 European countries. It is a contact sport where injuries are inevitable. In this study, injuries causing more than one week of absence from game or practise were registered during the 1991 preseason and season. A total of 112 injuries was reported among 684 players. Knees were most vulnerable to injury (28.6%) followed by ankle injuries (16.7%). Operations were performed on 28 (25%) of the injured players. Catastrophic injuries can occur in this sport, but none has happened in Finland during the 12 years for which the sport has been practised. The skill level was not a contributing factor. The frequency of injuries and their profile closely resemble those in US-based studies so it is suggested that the precautions and preventive measures recommended in the USA should be applied and followed in Europe.
Bioengineering of living renal membranes consisting of hierarchical, bioactive supramolecular meshes and human tubular cells
Authors: Patricia Y.W. Dankers, Jasper M. Boomker, Ali Huizinga-van der Vlag, Eva Wisse, Wilco P.J. Appel, Frank M.M. Smedts, Martin C. Harmsen, Anton W. Bosman, W. Meijer, Marja J.A. van Luyn
Journal: Biomaterials (2010)
Azole-resistant invasive aspergillosis in a patient with acute myeloid leukaemia in Germany
Authors: A Hamprecht, D Buchheidt, J J Vehreschild, O A Cornely, B Spiess, G Plum, T V Halbsguth, N Kutsch, D Stippel, P Kahl, T Persigehl, A Steinbach, B Bos, M Hallek, M J Vehreschild
Journal: Eurosurveillance (2012)

We report the first culture-proven case of invasive aspergillosis (IA) caused by azole-resistant Aspergillus fumigatus in a patient with acute myeloid leukaemia in Germany. IA presented as breakthrough infection under posaconazole prophylaxis. Analysis of the resistance mechanism revealed the TR/L98H mutation in the cyp51A gene, which indicates an environmental origin of the strain. This case underscores the need for monitoring azole resistance in Aspergillus spp. and for routine susceptibility testing of moulds.
Tumor–Stroma Interaction: Revealing Fibroblast-Secreted Exosomes as Potent Regulators of Wnt-Planar Cell Polarity Signaling in Cancer Metastasis
Authors: Valbona Luga, Jeffrey L. Wrana
Journal: Cancer Research (2013)

Cancer-associated fibroblasts (CAF) regulate tumor progression, but their role in cancer metastasis remains largely unexplored. Exosomes are secreted microvesicles that are emerging as potent mediators of cell-cell communication that are of particular importance in tumor-stroma interactions. The Wnt-planar cell polarity (PCP) pathway is the primary regulator of convergent extension cell movements during vertebrate development, but the role of this signaling pathway in cancer cell migration and metastasis has been unclear. Recently, we revealed that fibroblasts secrete exosomes that promote breast cancer cell (BCC) protrusive activity, motility, and metastasis by activating autocrine Wnt-PCP signaling in BCCs. Moreover, we showed that Wnt ligands produced by BCCs tether to fibroblast exosomes upon trafficking of exosomes in BCCs. These findings have several implications that motivate promising future research in the fields of tumor-stroma communication, exosome function, and Wnt-PCP signaling in cancer metastasis.
THE USE OF ATROPINE AS AN AID TO THE DIAGNOSIS OF TYPHOID AND PARATYPHOID A AND B INFECTIONS: (Preliminary Note.)
Authors: H. F. Marris
Journal: BMJ (1916)

Extension is applied to the leg and the limb suspended, on a bent Thomas knee splint, by 4-in.rubber slings.The back of the knee-joint is supported on a bent per- forated zinc splint reinforced by aluminium strips, which is, in turn, suspended from the Thomas splint by rubber .~~~Thomas splint a4apted for excision of knee.
Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention.
Authors: Dowhan Ahn, Yuqiang Ge, Peter K Stricklett, Pritmohinder Gill, Deborah Taylor, Alisa K Hughes, Masashi Yanagisawa, Lance Miller, Raoul D Nelson, Donald E Kohan
Journal: Journal of Clinical Investigation (2004)

In vitro studies suggest that collecting duct-derived (CD-derived) endothelin-1 (ET-1) can regulate renal Na reabsorption; however, the physiologic role of CD-derived ET-1 is unknown. Consequently, the physiologic effect of selective disruption of the ET-1 gene in the CD of mice was determined. Mice heterozygous for aquaporin2 promoter Cre recombinase and homozygous for loxP-flanked exon 2 of the ET-1 gene (called CD-specific KO of ET-1 [CD ET-1 KO] mice) were generated. These animals had no CD ET-1 mRNA and had reduced urinary ET-1 excretion. CD ET-1 KO mice on a normal Na diet were hypertensive, while body weight, Na excretion, urinary aldosterone excretion, and plasma renin activity were unchanged. CD ET-1 KO mice on a high-Na diet had worsened hypertension, reduced urinary Na excretion, and excessive weight gain, but showed no differences between aldosterone excretion and plasma renin activity. Amiloride or furosemide reduced BP in CD ET-1 KO mice on a normal or high-Na diet and prevented excessive Na retention in salt-loaded CD ET-1 KO mice. These studies indicate that CD-derived ET-1 is an important physiologic regulator of renal Na excretion and systemic BP.
Neutrophils from p40<i>phox−/−</i> mice exhibit severe defects in NADPH oxidase regulation and oxidant-dependent bacterial killing
Authors: Chris D. Ellson, Keith Davidson, G. John Ferguson, Rod O'Connor, Len R. Stephens, Phillip T. Hawkins
Journal: The Journal of Experimental Medicine (2006)

The generation of reactive oxygen species (ROS) by the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex plays a critical role in the antimicrobial functions of the phagocytic cells of the immune system. The catalytic core of this oxidase consists of a complex between gp91phox, p22phox, p47phox, p67phox, p40phox, and rac-2. Mutations in each of the phox components, except p40phox, have been described in cases of chronic granulomatous disease (CGD), defining their essential role in oxidase function. We sought to establish the role of p40phox by investigating the NADPH oxidase responses of neutrophils isolated from p40phox−/− mice. In the absence of p40phox, the expression of p67phox is reduced by ∼55% and oxidase responses to tumor necrosis factor α/fibrinogen, immunoglobulin G latex beads, Staphylococcus aureus, formyl-methionyl-leucyl-phenylalanine, and zymosan were reduced by ∼97, 85, 84, 75, and 30%, respectively. The defect in ROS production by p40phox−/− neutrophils in response to S. aureus translated into a severe, CGD-like defect in the killing of this organism both in vitro and in vivo, defining p40phox as an essential component in bacterial killing.
Lipid length controls antigen entry into endosomal and nonendosomal pathways for CD1b presentation
Authors: D. Branch Moody, Volker Briken, Tan-Yun Cheng, Carme Roura-Mir, Mark R. Guy, David H. Geho, Mark L. Tykocinski, Gurdyal S. Besra, Steven A. Porcelli
Journal: Nature Immunology (2002)
Early appearance of germinal center–derived memory B cells and plasma cells in blood after primary immunization
Authors: Elizabeth J. Blink, Amanda Light, Axel Kallies, Stephen L. Nutt, Philip D. Hodgkin, David M. Tarlinton
Journal: The Journal of Experimental Medicine (2005)

Immunization with a T cell-dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated V(H) genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1-expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220(+) memory B cells, and this is sufficient to account for the process of affinity maturation.
Lack of association of rare alleles in the HRAS variable number of tandem repeats (VNTR) region with adult glioma
Authors: Pengchin Chen, John K. Wiencke, Kathleen Conway, Sharon N. Edmiston, Rei Miike, Margaret Wrensch
Journal: Neuro-Oncology (2000)

HRAS rare alleles have been associated with the increased susceptibility to a variety of cancers. In the present study we examined the hypothesis that HRAS rare alleles are a risk factor for adult glioma in a population-based case-control study of adult glioma in six San Francisco Bay Area counties. We compared the prevalence of rare alleles in the variable number of tandem repeats region of HRAS in the germline DNA from 73 white adults who had gliomas with that of 65 controls. Overall, the prevalence of rare alleles in cases was not different from the prevalence of those in controls according to two definitions of rare alleles. We found that 25 of 73 (34%) of cases versus 25 of 65 (38%) of controls had at least one allele that was not 30, 46, 69, or 87 repeats; 4 of 73 (5%) of cases versus 6 of 65 (9%) of controls carried one or more alleles with 33, 39, 42, 53, 59, 63, 68, 105, or 114 repeats. The proportion of rare alleles was somewhat higher among subjects with anaplastic astrocytoma. Among women, cases were less likely than controls to have HRAS rare alleles, whereas among men, cases were slightly more likely to have HRAS rare alleles, but none of these results approach statistical significance. Our data do not suggest an excess of HRAS rare alleles among adult glioma cases.
Vitronectin is implicated as the matrix takes control of neointima formation
Authors: A Newby
Journal: Cardiovascular Research (2002)

See article by Dufourcq et al. [9] ( pages 953 -963) in this volume [9] expands their previous finding [10] that this issue.SMC can synthesise another multiadhesive glycoprotein, vitronectin.Only low levels of vitronectin are present by The normal blood vessel wall contains two functionally immunocytochemistry in the interstitial matrix of uninjured distinct types of vascular extracellular matrix, namely blood vessels.Synthesis of vitronectin is also sluggish by basement membranes and interstitial matrix.A basement in situ hybridisation in contractile SMCs [9], as is synmembrane consisting of type IV collagen, the multi-adhe-thesis of other interstitial matrix components [11].Moresive glycoprotein, laminin, and a variety of heparan over, receptors for vitronectin (avb3 and a b5 integrins)
Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case-control study
Authors: C Gilham, J Peto, J Simpson, E Roman, T O B Eden, M F Greaves, F E Alexander
Journal: BMJ (2005)

To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK.
Etanercept or intravenous immunoglobulin attenuates expression of genes involved in post-myocardial infarction remodeling
Authors: D GURANTZ, A YNDESTAD, B HALVORSEN, O LUNDE, J OMENS, T UELAND, P AUKRUST, C MOORE, J KJEKSHUS, B GREENBERG
Journal: Cardiovascular Research (2005)

Persistently elevated levels of inflammatory cytokines such as tumor necrosis factor (TNF)alpha after acute myocardial infarction (MI) may contribute to maladaptive ventricular remodeling. The aim of the present study was to examine the effects of immunomodulatory therapy with recombinant soluble TNF receptor (TNFR:Fc) or intravenous immunoglobulin (IVIg) on left and right ventricular post-MI remodeling in rats.Adult male Sprague-Dawley rats were subjected to MI by left coronary artery ligation and randomized to treatment with vehicle, TNFR:Fc, or IVIg and sacrificed after 7 days. The main findings were that: (i) TNFR:Fc- and IVIg-treated rats developed less right ventricular (RV) hypertrophy compared to vehicle-treated controls. (ii) LV and arterial pressures in post-MI rats were not affected by the TNFR:Fc or IVIg treatment. (iii) As determined by real-time RT-PCR, both treatments reduced the expression of the hypertrophy-related genes, atrial natriuretic peptide and the ratio of beta/alpha-myosin heavy chains, and genes related to extracellular matrix remodeling (i.e., collagens I and III, matrix metalloproteinase [MMP]-2 and its tissue inhibitor TIMP-1) in the non-ischemic segment of LV and, in particular, in the RV. (iv) Treatment with IVIg, but not TNFR:Fc, reduced MMP-2 zymographic activity in the RV and the expression of genes for TNFalpha and monocyte chemoattractant protein-1.Therapy targeted directly against TNFalpha (i.e., TNFR:Fc) and a more general immunomodulatory approach (i.e., IVIg) in the acute phase of MI attenuates the cardiac remodeling process and expression of genes that are involved. These findings raise the possibility that initiation of immunomodulatory therapy post-MI could be beneficial in preventing the later development of heart failure.
Effect of positioning and bracing on passive position sense of shoulder joint
Authors: B Ulkar, B Kunduracioglu, C Çetin, R S Güner
Journal: British Journal of Sports Medicine (2004)

To examine the effects of positioning and sleeve type bracing on passive position sense of shoulder joints of healthy untrained subjects.A cross over study was carried out on 26 subjects (13 male, 13 female) with a proprioception measurement device. The selected method of testing was passive reproduction of a target angle. Both shoulder joints of all the subjects were evaluated with and without a compressive neoprene sleeve type of brace at two different start positions (45 degrees internal rotation, 75 degrees external rotation) with an angular rotational movement at a constant speed of 0.5 degrees /s. The angular displacements from the target angles at the end of the reproduction tests were recorded as position sense deficit scores.The overall mean (SD) deficit score (0.99 (0.06)) was significantly (p<0.001) lower with the brace than without, and the overall mean deficit score was significantly (p<0.001) higher at the 45 degrees internal rotation start position than at the 75 degrees external rotation start position. However, there was no significant (p>0.05) interaction between brace application and start position.Terminal limits of range of motion facilitate the position sense of shoulder joints. Compressive brace application improves the passive positioning sense possibly by stimulating cutaneous mechanoreceptors.
Multiagent Chemotherapy and Deferred Radiotherapy in Infants With Malignant Brain Tumors: A Report From the Children’s Cancer Group
Authors: J. Russell Geyer, Richard Sposto, Mark Jennings, James M. Boyett, Richard A. Axtell, David Breiger, Emmett Broxson, Bernadine Donahue, Jonathan L. Finlay, Joel W. Goldwein, Linda A. Heier, Dennis Johnson, Claire Mazewski, Douglas C. Miller, Roger Packer, Diane Puccetti, Jerilynn Radcliffe, May Lin Tao, Tania Shiminski-Maher
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate response rate, event-free survival (EFS), and toxicity of two chemotherapeutic regimens for treatment of children younger than 36 months with malignant brain tumors and to estimate control intervals without irradiation in children with no residual tumor after initial surgery and induction chemotherapy and with delayed irradiation in patients with residual tumor or metastatic disease at diagnosis. Patients and Methods Patients were randomly assigned to one of two regimens of induction chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide v vincristine, carboplatin, ifosfamide, and etoposide). Maintenance chemotherapy began after induction in children without progressive disease. Children with no residual tumors after induction therapy and no metastatic disease at diagnosis were not to receive radiation therapy unless their tumors progressed. Results Two hundred ninety-nine infants were enrolled. Forty-two percent of patients responded to induction chemotherapy. At 5 years from study entry, the EFS rate was 27% ± 3%, and the survival rate was 43% ± 3%. There was no significant difference between the two arms in terms of response rate or EFS. For medulloblastoma, supratentorial primitive neuroectodermal tumor, ependymoma, and rhabdoid tumors, 5-year EFS rates were 32% ± 5%, 17% ± 6%, and 32% ± 6%, and 14% ± 7%, respectively. Fifty-eight percent of patients who were alive 5 years after study entry had not received radiation therapy. Conclusion Intensified induction chemotherapy resulted in a high response rate of malignant brain tumors in infants. Survival was comparable to that of previous studies, and most patients who survived did not receive radiation therapy.
Presence of Diabetes Risk Factors in a Large U.S. Eighth-Grade Cohort
Authors: T Baranowski, D M Cooper, J Harrell, K Hirst, F R Kaufman, M Goran, K Resnicow
Journal: Diabetes Care (2006)

OBJECTIVE—The study was conducted in 12 middle schools to determine the prevalence of diabetes, pre-diabetes, and diabetes risk factors in eighth-grade students who were predominantly minority and evaluate the feasibility of collecting physical and laboratory data in schools. RESEARCH DESIGN AND METHODS—Anthropometric measurements and fasting and 2-h post-glucose load blood draws were obtained from ∼1,740 eighth-grade students. RESULTS—Mean recruitment rate was 50% per school, 49% had BMI ≥85th percentile, 40.5% had fasting glucose ≥100 mg/dl, 0.4% had fasting glucose ≥126 mg/dl, and 2.0% had 2-h glucose ≥140 mg/dl and 0.1% ≥200 mg/dl. Mean fasting insulin value was 30.1 μU/ml, 36.2% had fasting insulin ≥30 μU/ml, and 2-h mean insulin was 102.1 μU/ml. Fasting and 2-h glucose and insulin values increased across BMI percentiles, and fasting glucose was highest in Hispanic and Native American students. CONCLUSIONS—There was a high prevalence of risk factors for diabetes, including impaired fasting glucose (≥100 mg/dl), hyperinsulinism suggestive of insulin resistance (fasting insulin ≥30 μU/ml), and BMI ≥85th percentile. These data suggest that middle schools are appropriate targets for population-based efforts to decrease overweight and diabetes risk.