tbuckley/cabot-search huggingface dataset:
Abstract 5271: Homozygous deletion of the activin A receptor, type IB gene is associated with an aggressive cancer phenotype in pancreatic cancer
Authors: Yosuke Togashi, Hiroki Sakamoto, Hidetoshi Hayashi, Masato Terashima, Marco A. de Velasco, Yoshihiko Fujita, Yasuo Kodera, Kazuko Sakai, Shuta Tomida, Masayuki Kitano, Masatoshi Kudo, Kazuto Nishio
Journal: Cancer Research (2014)

Abstract Background: Transforming growth factor, beta (TGFB) signal is considered to be a tumor suppressive pathway based on the frequent genomic deletion of the SMAD4 gene in pancreatic cancer (PC); however; the role of the activin signal, which also belongs to the TGFB superfamily, remains largely unclear. Methods and Results: We found a homozygous deletion of the activin A receptor, type IB (ACVR1B) gene in 2 out of 8 PC cell lines using array-comparative genomic hybridization, and the absence of ACVR1B mRNA and protein expression was confirmed in these 2 cell lines. Activin A stimulation inhibited cellular growth and increased the phosphorylation level of SMAD2 and the expression level of p21CIP1/WAF1 in the Sui66 cell line (wild-type ACVR1B and SMAD4 genes) but not in the Sui68 cell line (homozygous deletion of ACVR1B gene). Stable ACVR1B-knockdown using short hairpin RNA cancelled the effects of activin A on the cellular growth of the PC cell lines. In addition, ACVR1B-knockdown significantly enhanced the colony formation abilities and cellular growth, compared with controls. In a xenograft study, ACVR1B-knockdown resulted in a significantly elevated level of tumorigenesis and a larger tumor volume, compared with the control. Furthermore, in clinical samples, 6 of the 29 PC samples (20.7%) carried a deletion of the ACVR1B gene, while 10 of the 29 samples (34.5%) carried a deletion of the SMAD4 gene. Of note, 5 of the 6 samples with a deletion of the ACVR1B gene also had a deletion of the SMAD4 gene. Conclusion: We identified a homozygous deletion of the ACVR1B gene in PC cell lines and clinical samples and proposed that the deletion of the ACVR1B gene may mediate an aggressive cancer phenotype in PC. Our findings provide novel insight into the role of the activin signal in PC. Citation Format: Yosuke Togashi, Hiroki Sakamoto, Hidetoshi Hayashi, Masato Terashima, Marco A. de Velasco, Yoshihiko Fujita, Yasuo Kodera, Kazuko Sakai, Shuta Tomida, Masayuki Kitano, Masatoshi Kudo, Kazuto Nishio. Homozygous deletion of the activin A receptor, type IB gene is associated with an aggressive cancer phenotype in pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5271. doi:10.1158/1538-7445.AM2014-5271
Molecular and Cytogenetical Alterations Induced by Environmental Cigarette Smoke in Mice Heterozygous for <i>Fhit</i>
Authors: Silvio De Flora, Francesco D'Agostini, Alberto Izzotti, Nicola Zanesi, Carlo M. Croce, Roumen Balansky
Journal: Cancer Research (2007)

Abstract Previous studies in humans and animal models provided evidence that the Fhit gene is an early target for cigarette smoke. We compared the induction of a variety of molecular and cytogenetical alterations in B6-129(F1) mice, either wild type or Fhit+/−, after whole-body exposure to environmental cigarette smoke (ECS) for 15 consecutive days. Both mouse genotypes responded to ECS with a loss of Fhit protein in the bronchial epithelium, accompanied by induction of apoptosis and stimulation of cell proliferation. ECS induced formation of bulky DNA adducts in whole lung. In addition, ECS caused cytogenetical damage both in the respiratory tract and at a systemic level, as shown by a significant increase of micronucleus frequency in pulmonary alveolar macrophages, bone marrow polychromatic erythrocytes, and peripheral blood normochromatic erythrocytes of both wild-type and Fhit+/− mice. These results are compared with those generated in other species, strains, and genotypes of rodents exposed to ECS that we investigated previously. Although the loss of Fhit protein in the bronchial epithelium of ECS-exposed B6-129(F1) mice provides further evidence that the Fhit gene is an early molecular target for ECS, heterozygosity for Fhit does not seem to confer an increased susceptibility of mice in terms of the investigated early biomarkers. [Cancer Res 2007;67(3):1001–6]
Abstract P6-15-17: Synergy of Ixabepilone and Dasatinib in Triple Negative Breast Cancer Cell Lines
Authors: RR Ismail-Khan, DC Marichion, CL Cubitt, JM. Lancaster
Journal: Cancer Research (2010)

Abstract Background: Treatment options are very limited for breast cancers that do not express HER2 or estrogen and progesterone receptors (Triple Negative Breast Cancer; TNBC). Dasatinib is an orally active small molecule inhibitor of the src kinase. It has been proposed that dasatinib inhibits growth of breast cancer cells by modulating epidermal growth factor receptor (EGFR) signaling. Approximately 70% of breast cancers over express EGFR family members as well as c-Src. Src is co-expressed with at least one of the EGFRs. Both src and EGFR1 expression have been associated with TNBC. Dasatinib has previously shown activity as a single agent in TNBC cell lines. However, dasatinib has limited single agent activity in a cohort of chemotherapy refractory TNBC patients according to a phase I/II study. We believe that dasatinib may sensitize breast cancer cells to anti-mitotic agents. Ixabepilone is a potent anti-mitotic agent that has shown significant response in TNBC patients, both in the neoadjuvant setting and in the metastatic setting, including those cancers that are taxane refractory. Therefore, combining these two drugs may have utility in this setting and may lead to inhibition of tumor cell proliferation, invasion, metastasis, angiogenesis, and tumor cell survival. Objectives: To study the activity of dasatinib combined with Ixabepilone in breast cancer cell lines. Methods: A panel of 8 breast cancer cell lines was used in these experiments. These included MCF-7(ER+), T-47D (ER +), SKBR3 (HER2+), and five triple negative cell lines: BT-549, HS578T, MDA-MB-157, MDA-MB-231, MDA-MB-436. First, these cell lines were evaluated for src expression by Western blot as well as sensitivity to dasatinib alone, ixabepilone alone and then the combination of these two drugs using a high-throughput, 384- well CellTiter-Blue cell viability assay. Percent viability was calculated from four replicate cell wells after 72-hour drug incubation and IC50s were determined. Experiments were repeated a minimum of three times. Synergistic, additive, or antagonistic effects were determined using the combination index (CI) method developed by Chou and Talalay. Results: TNBC cell lines expressed higher levels of src protein than cell lines with positive expression of HER2, ER and/or PR by Western blot analysis. Viability assays suggested a correlation between src expression and dasatinib IC50. Combinations of dasatinib and ixabepilone were determined to have combinational indexes &amp;lt;1 in all cell lines tested, suggestive of synergistic activity. Conclusion: This study demonstrates that in a range of breast cell lines with varying levels of src expression, dasatinib combined with ixabepilone is a synergistic combination and may prove to be beneficial to patients with very limited treatment options. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-15-17.
Sidney Temple Armstrong
Authors: K J Armstrong
Journal: BMJ (2009)

Sidney Temple Armstrong was born on 30 June 1919 to Drs John and Maria Armstrong. He studied medicine at Queen’s University, Belfast, during the second world war, mixing his studies with ARP (Air Raid Precautions) duties. Qualifying in 1946, he became a houseman in the Waveney Hospital, Ballymena, before moving to England to work at Otley General …
Acute intravenous cocaine causes transient depression followed by enhanced left ventricular function in conscious dogs.
Authors: B S Stambler, K Komamura, T Ihara, R P Shannon
Journal: Circulation (1993)

Prior studies in experimental canine models have demonstrated that intravenous cocaine administration causes myocardial depression. The purpose of the present study was to establish the mechanisms of cocaine's actions on myocardial and left ventricular performance after single intravenous bolus doses in conscious, chronically instrumented dogs, in which the full autonomic influences of cocaine would be manifest.In the intact state, cocaine (1 mg/kg) caused a transient decrease in left ventricular dP/dt (baseline; 3,086 +/- 107 mm Hg/sec; 2.5 minutes, 2,649 +/- 114 mm Hg; p < 0.05) followed by a 25 +/- 4% increase in left ventricular dP/dt that peaked at 15 minutes (left ventricular dP/dt, 3,751 +/- 127 mm Hg/sec, p < 0.01) and remained elevated during the 30-minute period of observation. Both the initial depression and the sustained increase in left ventricular contractile response were dose related. The increase in left ventricular dP/dt persisted under circumstances in which the responses were normalized for changes in heart rate and preload that accompanied cocaine administration. The positive inotropic effects were abolished by full autonomic or selective beta-adrenergic blockades. Finally, both cardiac output (baseline, 2,461 +/- 142 min/mL; peak [5 minutes], 3,434 +/- 218 mL/min; p < 0.05) and left ventricular stroke work (baseline, 39 +/- 5 g.m; peak, 49 +/- 6 g.m; p < 0.05) were increased at all times after cocaine administration, suggesting that pump performance was enhanced, despite early reductions in myocardial contractility. Similarly, indexes of early diastolic filling were enhanced despite transient early prolongation in isovolumic relaxation.Acute intravenous cocaine administration (0.1-2 mg/kg) has a biphasic effect on myocardial and left ventricular function with a transient depression followed by significant sustained increases in left ventricular contractility. The results are in keeping with an early local effect followed by significant adrenergic stimulation, which may be obscured by anesthesia or masked by changes in loading conditions.
Thyroid Uptake of Gallium in Graves?? Disease
Authors: JEFFREY C. ALLARD, VICTOR W. LEE, PETER FRANKLIN
Journal: Clinical Nuclear Medicine (1988)

A patient with hyperthyroid Graves' disease presented with ptosis, leading to a workup for myasthenia gravis. An enlarged thymus gland was noted on computed tomography. A scan with gallium-67 citrate showed prominent and diffuse thyroid gland activity as well as prominent lacrimal activity. This finding of thyroid uptake of gallium led to the correct diagnosis of Graves' disease. Such a finding has not been reported previously. The associated thymic, thyroid, and orbital findings in Graves' disease are discussed.
Horizon: Living with ADHD
Authors: Charles Essex
Journal: BMJ (2005)

BBC 2, 3 February at 9 pm Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> W hen I see a child with a disability or behaviour problem I know that I see them for 30 minutes and then move on to the next patient. The parents cannot move on. This programme showed some of what parents of children with attention-deficit hyperactivity disorder (ADHD) have to put up with. As cameras followed two families for six months the parents told their experiences without interruption from an interviewer. The viewer saw some of the day to day behaviour of children with ADHD … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Observer variation in computed tomography of pleural lesions in subjects exposed to indoor asbestos
Authors: H. De Raeve, J.A. Verschakelen, P.A. Gevenois, P. Mahieu, G. Moens, B. Nemery
Journal: European Respiratory Journal (2001)

To assess the reliability of computed tomography (CT) in detecting discrete pleural lesions, the interobserver and intra-observer variability in reading the conventional and high-resolution CT (HRCT) scans of 100 volunteers, who had worked for ≥10 yrs in a building with known asbestos contamination, was evaluated. In the first session, pleural abnormalities were detected by a single radiologist (A 1 ) in 13 subjects. In the second session, the scans were read again independently by the same radiologist (A 2 ) and two other experienced radiologists (B, C). The final decision for the presence of pleural lesions was made in a final consensus reading. This gave a diagnosis of pleural abnormalities in 18 subjects, of whom eight (44%) had been detected by all three readers, five (28%) by two readers and four (22%) by only one reader; one scan, rated normal by all readers during the second session, was reconsidered because pleural abnormalities had been noted at the first reading (A 1 ). The intra-observer agreement for reader A was good (kappa (κ) 0.68) but the interobserver agreement between the readers was only fair to moderate (weighted κ: A 2 -B=0.43, A 2 -C=0.45, B-C=0.26) in the second reading session. In conclusion, when looking for the prevalence of pleural lesions in indoor asbestos exposed subjects, the potential lack of consistency in reporting the presence of small pleural abnormalities must be borne in mind and strict precautions must be taken.
Effect of Chloride on Renin and Blood Pressure Responses to Sodium Chloride
Authors: THEODORE A. KOTCHEN
Journal: Annals of Internal Medicine (1983)

Both the inhibition of renin release by sodium chloride and salt-sensitive hypertension have been attributed to sodium. We evaluated the contribution of chloride to these responses to sodium chloride. In the Sprague-Dawley rat, acute and chronic administration of sodium salts other than sodium chloride failed to suppress plasma renin activity, whereas renin was inhibited by both sodium chloride and by selective chloride (without sodium) loading. Plasma renin activity was stimulated by selective chloride depletion. Similarly, in humans, plasma renin activity was suppressed by sodium chloride but not by sodium bicarbonate infusion. In a preliminary study in the Dahl salt-sensitive rat, in contrast to sodium chloride loading, sodium bicarbonate loading failed to produce hypertension. Thus, both the renin and possibly the blood pressure responses to sodium chloride are dependent on chloride.
Advances in Surgical Practice 1
Authors: R. Dale Liechty
Journal: JAMA (1987)

Because it has only a starkly barren, cloth cover, this slender volume could contain a collection of poetry. Inside, however, we find a collection of five surgical subjects: cancer of the esophagus and thyroid gland, carcinoid tumors, hyperthyroidism, and pancreatic infections. The author has had a substantial experience with these topics "which have received special study during the past 20 years." Writing from West Bengal, India, Dr Chatterjee has produced five well-referenced discussions, intending these chapters for "those studying for higher diplomas in surgery." Generally the discussions are thorough, comprehensive, and up-to-date. For example, the author devotes three pages to the carcinoid syndrome, discussing the classic midgut variety (diarrhea, flushing, wheezing, and right ventricular lesions) and the foregut variety (marked flushing, lacrimation, facial edema, and left ventricular lesions). He includes a discussion of the relevant humoral agents: serotonin, histamine, substance P, prostaglandins, and 5-hydroxytryptophan. Other chapters are similarly detailed. Dr
Isolation and purification of a major allergen from <i>Parietaria officinalis</i> pollen
Authors: A. Giuliani, C. Pini, S. Bonini, N. Mucci, L. Ferroni, G. Vicari
Journal: Allergy (1987)

A major allergen of Parietaria officinalis , a species responsible for a large number of respiratory allergies in Mediterranean areas, has been identified and characterized. This allergen (Pol) was found in the fraction which precipitates between 70 and 100% ammonium sulphate saturation. Pol showed a molecular weight of 15,000 daltons as determined by SDS‐PAGE and HPLC. The pI of Pol was in the pH region 4‐6, IEF showing four major bands. Two major bands were shown by CIE, CRIE and immuno‐blotting; major contaminants or aggregates were also revealed by the latter technique and by HPLC. Pol showed an allergic specific activity 2 times higher than the crude extract; moreover it was shown to be a major allergen since it inhibited 29 out of 30 sera from allergic patients sensitive to P. officinalis.
The size and histological appearances of mesenteric lymph nodes in Crohn's disease
Authors: M. G. Cook
Journal: Gut (1972)

The size of the related lymph nodes and their histology has been correlated in 34 specimens of Crohn's disease. Granulomata were shown not to affect the maximum diameter of the lymph nodes nor to be more frequent in large nodes. The enlargement of lymph nodes appeared to be due to simple, non-specific, reactive changes. Granulomatous lymph nodes were found in 38% of all our cases of Crohn's disease and in 63% of those cases with granulomata in the bowel wall. One case was found with granulomata in the lymph nodes which were not seen in the bowel wall. The mesenteric lymph nodes of 22 cases of ulcerative colitis were shown to be not significantly different in size from those of Crohn's disease. The diameter of the lymph nodes on the histological section was shown to underestimate the diameter of nodes in the fresh state by a factor of 1.5.
388. Chromosomal Rearrangements in Mammalian Cells Are Induced at High Frequency by the Bacteriophage Derived Integrase phiC31
Authors: Anja Ehrhardt, Jeffrey A. Engler, Hui Xu, Athena Cherry, Mark A. Kay
Journal: Molecular Therapy (2006)

Recent reports on insertional mutagenesis due to integration of gene therapy vectors into the host genome have raised concerns about the genetic manipulation of somatic cells. Previously, it was demonstrated that the integrase phiC31 derived from a Streptomyces phage mediates site-specific integration into the host genome of mammalian cells in vitro and in vivo by recombining the attB recognition site in an episomal plasmid and one or more pseudo attP sites in the host chromosomes. However, there is strong evidence that cryptic lox sites for Cre mediated integration are present in the eukaryotic genome which result in chromosomal translocations. Thus, we investigated whether or not cryptic phiC31 recognition sites may result in chromosomal rearrangements. In this study we found that the integrase phiC31 induced chromosomal rearrangements in the mammalian host genome with a frequency of up to 13% as demonstrated by integration site analysis and limited karyotyping studies. Single cell clones from in human hepatoma cells (Huh-7), human embryonic kidney cells (293), and the human colon carcinoma cell line HCT116 were grown and sites of insertion were characterized based on an established plasmid rescue protocol which allows identification of both chromosomal DNA sequences flanking the integrated transgene. Out of 81 independent integration events analyzed, 7 (8.6%) integrated into chromosome 19 (19q13.31) and 9 (11%) into chromosome 12 (12q22). Most importantly, of all independent integration sites analyzed 13% were found to contain an integrated transgene which was flanked by DNA sequences originated from two different chromosomes. This observation strongly suggested that chromosomal rearrangements might have occurred. This assumption is further supported by the fact that if one uses the same experimental approach this phenomenon has not been reported in over 1000 Sleeping Beauty mediated integration events and in less than 0.25% (1 out of 400) of all sites of insertion after adeno-associated virus (AAV) mediated integration. To confirm chromosomal translocations, we determined the genotype of single cell clones by karyotype analysis in HCT116 cells, a cell line for which the chromosomal content is relatively stable and well characterized. In sharp contrast to wildtype HCT116 cells, all twenty-four metaphases examined in cell clone HCT-1A7 had the same chromosomal abnormality on chromosome 22 band q13, which confirmed our plasmid rescue data. For some clones, a mixture of transgenes flanked by DNA sequences originated from the same but also two different chromosomes was identified. Taken together, his feature will introduce novel ways to genetically modify mammalian cells and to study the fate of cells with chromosomal translocations but suggests that additional safety studies will be required before the use of this integrase in gene therapy approaches.
Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing.
Authors: R M Hershberg, P E Framson, D H Cho, L Y Lee, S Kovats, J Beitz, J S Blum, G T Nepom
Journal: Journal of Clinical Investigation (1997)

Intestinal epithelial cells express a low level of HLA class II molecules constitutively, with elevated levels seen in the setting of mucosal inflammation including inflammatory bowel disease. The ability of intestinal epithelial cells to act as antigen presenting cells for alphabeta CD4(+) T lymphocytes was examined through a molecular analysis of the HLA class II antigen processing pathway. We have shown that intestinal epithelial cells contain abundant constitutive levels of the cathepsin proteases proven to function in HLA class II mediated antigen presentation. Activation of these cells by gamma-IFN induced the expression of invariant chain and HLA-DM alphabeta, thus facilitating the formation of compact, SDS-stable HLA- DR alphabeta heterodimers. Using HLA-DR-restricted T cells and retroviral mediated gene transfer of HLA-DR alleles into the intestinal epithelial cell lines HT-29 and T84, we demonstrated efficient antigen processing and presentation to CD4(+) T lymphocytes in the presence of the proinflammatory cytokine gamma-IFN. The class II processing pathway and presentation in the presence of gamma-IFN was indistinguishable from that observed with a conventional antigen presenting cell. Antigen processing also occurred in intestinal epithelial cells in the absence of gamma-IFN, and in contrast to that seen after stimulation with gamma-IFN, required high concentration of antigen and was not inhibited by the protease inhibitor leupeptin. These data suggest the use of two distinct pathways of HLA class II antigen processing in enterocytes with differential immunomodulatory properties in the presence or absence of mucosal inflammation.
Small falls in weight can improve health provided they are long term, says NICE
Authors: N. Hawkes
Journal: BMJ (2014)

Weight loss programmes that focus on diet, activity, and lifestyle are cost effective even if the weight loss is small, so long as the improvement is maintained for the rest of life, the National Institute for Health and Care Excellence (NICE) has concluded.1

In new guidance on lifestyle weight management programmes, NICE says that £100 (€123; $170) spent on putting an individual through a 12 week course is cost effective if at least 1 kg of weight is lost and if this achieves a permanent change in the person’s weight trajectory—that is, for the rest of that person’s life, his or her weight is 1 kg less than it otherwise would have been. For programmes costing £500 per head to be cost effective, the weight loss must be 2 kg; for £1000 programmes, 3 kg. …