tbuckley/cabot-search huggingface dataset:
Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma
Authors: Wei Kang, Joanna HM Tong, Raymond WM Lung, Yujuan Dong, Junhong Zhao, Qiaoyi Liang, Li Zhang, Yi Pan, Weiqin Yang, Jesse CS Pang, Alfred SL Cheng, Jun Yu, Ka Fai To
Journal: Molecular Cancer (2015)

MicroRNAs (miRNAs) have been reported to play an important role in tumorigenesis. In this study, the role of miR-15a and miR-16-1 in gastric adenocarcinoma (GAC) was investigated. The expression of miR-15a and miR-16-1 in cell lines and primary tumors was examined by miRNA qRT-PCR. Proliferative assays, colony formation, cell invasion and migration, flow cytometry analysis and in vivo study were performed by ectopic expression of miR-15a and miR-16-1. The putative target genes of miR-15a and miR-16-1 were explored by TargetScan and further validated. We found that miR-15a and miR-16-1 were down-regulated in GAC cell lines and primary tumor samples compared with normal gastric epithelium. Functional study demonstrated that ectopic expression of miR-15a and miR-16-1 suppressed cell proliferation, monolayer colony formation, invasion and migration, and xenograft formation in vivo. In addition, miR-15a and miR-16-1 induced G0/G1 cell cycle arrest which was further confirmed by Western blot and qRT-PCR of related cell cycle regulators. YAP1 was confirmed to be a functional target of miR-15a and miR-16-1 in GAC. YAP1 re-expression partly abrogated the inhibitory effect of miR-15a and miR-16-1 in GAC cells. In clinical samples, YAP1 protein expression shows negative correlation with miR-15a and miR-16-1 expression. In conclusion, targeting YAP1 by tumor suppressor miRNA miR-15a and miR-16-1 plays inhibitory effect and this might have a therapeutic potential in GAC.
Alcohol drinking and risk of subsequent hospitalisation with pneumonia
Authors: J. B. Kornum, K. M. Due, M. Norgaard, A. Tjonneland, K. Overvad, H. T. Sorensen, R. W. Thomsen
Journal: European Respiratory Journal (2011)

The dose-response relationship between alcohol consumption and pneumonia risk in healthy individuals is poorly understood. We examined 22,485 males and 24,682 females from Denmark who were aged 50-64 yrs. Subjects were without major chronic diseases at baseline and had a median follow-up of 12 yrs for first-time hospitalisation with pneumonia. 1,091 (males) and 944 (females) had pneumonia-related hospitalisation. Among males, the risk of pneumonia was increased for alcohol abstainers and those who drank large weekly amounts. The adjusted hazard ratios (HRs) for 0, 7-20, 21-34, 35-50 and >50 drinks·week(-1) were 1.49 (95% CI 1.00-2.21), 0.88 (95% CI 0.76-1.03), 0.87 (95% CI 0.72-1.05), 1.15 (95% CI 0.93-1.44) and 1.81 (95% CI 1.40-2.33), respectively, compared with 1-6 drinks·week(-1). The association between high alcohol intake and pneumonia persisted after controlling for subsequent chronic diseases. Among females, HRs for 0, 7-20, 21-35 and >35 drinks·week(-1) were 1.26 (95% CI 0.89-1.79), 1.01 (95% CI 0.88-1.17), 1.10 (95% CI 0.88-1.37) and 0.54 (95% CI 0.29-1.01), respectively. For the same moderate to high weekly alcohol amount, infrequent intake yielded higher pneumonia HRs than more regular intake in both sexes. Regular moderate alcohol intake is not associated with increased risk of hospitalisation for pneumonia. High weekly alcohol consumption in males and infrequent heavy drinking in both sexes may increase pneumonia risk.
Interaction between <i>BCL2</i> and <i>Interleukin-10</i> Gene Polymorphisms Alter Outcomes of Diffuse Large B-Cell Lymphoma following Rituximab Plus CHOP Chemotherapy
Authors: Yeon Hee Park, Sang Kyun Sohn, Jong Gwang Kim, Myung-Hoon Lee, Hong Suk Song, Min Kyoung Kim, Joo Seop Jung, Je-Joong Lee, Hyeoung Joon Kim, Dong Hwan Kim
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Rituximab may overcome bcl-2-mediated chemoresistance through the inhibition of interleukin-10 (IL-10)-mediated loops, thus down-regulating bcl-2 expression. We examined the effects of genetic variation in BCL2/IL10 gene loops on treatment outcomes of diffuse large B-cell lymphoma when treated with either CHOP or rituximab plus CHOP (R-CHOP) chemotherapy. Experimental Design: Four genotypes were tested including BCL2 -938 C&amp;gt;A (rs2279115), +21 A&amp;gt;G (rs1801018), IL10 -819 T&amp;gt;C (rs1800871), and -592 A&amp;gt;C (rs1800872) in patients receiving either R-CHOP (n = 125) or CHOP (n = 110). Results: IL10 SNPs, -819 TT/TC or -592 AA/AC genotypes correlated with improved CHOP response rates (P = 0.04). Neither polymorphism separately influenced the failure-free survival (FFS) or overall survival in patients, but the IL10 haplotype was associated with treatment outcomes after R-CHOP for FFS (P = 0.03) or progression (P = 0.007), whereas the -938 AA BCL2 genotype significantly affected overall survival (P = 0.04). An interactive effect between BCL2 and IL10 SNPs was significant in the group with both -938 AA BCL2 genotype and 1 to 2 copies of CC IL10 haplotype. This group showed a better FFS (P = 0.01) and a lower probability of progression (P = 0.004) compared with other genotype groups when treated with R-CHOP chemotherapy. Conclusions: These data indicated that R-CHOP chemotherapy resistance in diffuse large B-cell lymphoma may involve interactions between the BCL2 and IL10 genes.
Increasing immunosuppression despite high load of respiratory viruses: Fludarabine as rescue treatment in alloreactive lung disease
Authors: Bart Rottier, Martine Raphael, Jan Jaap Boelens
Journal: European Respiratory Journal (2011)

Background: Allo immune lung syndromes (alloLS) as Bronchiolitis obliterans syndrome and ideopathic pulmonary syndrome are life threatening complications after allogenic hematopoetic stem cell transplantation (HSCT) or lungtransplantation (LTX; rejection). Respiratory viral infections may trigger these alloLS. If conventional treatment with corticosteroids is not effective, 2nd line therapy may be needed.

Aim: To describe safety and efficacy of the T-cell depleting agent fludarabine to treat allo immuneLS in the presence of viral infections

Methods: We describe 5 patients (4 HSCT, 1 LTX) with steroid refractory alloLS who were therefore treated with fludarabine 30mg/m2 on a 3 weekly basis. Viral persistence of respiratory viruses was monitored by quantitative PCR before and during treatment.

Results: The five patients all initially had good engraftment, but developed respiratory complications. 4 patients were positive in BAL and/or nasopharyngeal aspirate with cycle threshold (CT values <30 for: rhinovirus (2), parainfluenza and RSV (1) and adenovirus (1)). 4/5 patients had initial response after mean 2.4 (range 1-4) courses. The LTX patient improved clinically as well as for FEV1 for 2 months and then had a relapse with progression of the alloLS. One patient died from aspergillus after 2 months. 3 patients had sustained response. Viral load (expressed in CT values) remained high in all patients, without occurrence of systemic disease.

Conclusions: Fludarabine is feasible and an effective 2nd line treatment of steroid refractory allo immune lung syndromes, without an increase in viral load. This empirical treatment now deserves a controlled study.
Effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular junctional area of the dog heart.
Authors: S Motomura, T Iijima, N Taira, K Hashimoto
Journal: Circulation Research (1975)

The effects of neurotransmitters injected into the posterior and the anterior septal artery on the automaticity of the atrioventricular (AV) junctional area were examined in the excised, blood-perfused canine AV node preparation. An AV rhythm of 57.4 +/- 2.8 beats/min (N = 28) developed after the destruction of the sinoatrial node. l-Norepinephrine injected into the anterior septal artery increased the frequency of AV rhythm, but l-norepinephrine injected into the posterior septal artery caused a pacemaker shift from the anterior septal artery area to the posterior septal artery area. Acetylcholine injected into the posterior septal artery blocked retrograde conduction but did not decrease the frequency of AV rhythm; however, acetylcholine injected into the anterior septal artery decreased AV rhythm but did not affect retrograde conduction. Destruction of the posterior septal artery area failed to change AV rhythm. The surgically separated anterior septal artery preparation had the same rate as did the AV node preparation. The posterior septal artery preparation had a definitely lower rate and responded to smaller doses of l-norepinephrine than did the AV node preparation. The results of the present study indicate that AV rhythm in the AV node originates in the area supplied by the anterior septal artery and that the area supplied by the posterior septal artery, which has extremely low automaticity, is highly responsive to l-norepinephrine, resulting in nodal tachycardia.
Do team gymnasts compete in spite of symptoms from an injury?
Authors: M L Harringe, S Lindblad, S Werner
Journal: British Journal of Sports Medicine (2004)

Gymnasts practise many hours a week, and symptoms from injuries do not seem to stop them from continuing with practice. They may even compete with symptoms from injuries, which could increase the risk of reinjury, or of the occurrence of a more severe injury.To investigate whether team gymnasts compete at high level in spite of symptoms from an injury.188 male and female competitors participating in the Swedish Cup for juniors and seniors answered a questionnaire about symptoms from injuries on the day of the competition.More than half the gymnasts (58%) competed despite having symptoms from an injury on the day of the competition. More seniors than juniors competed in spite of symptoms from an injury (p = 0.006). Two of three team gymnasts (65%) reported symptoms from the lower extremities and around one in five (22%) reported back symptoms. Fifty five per cent of the gymnasts reported recurrence of an injury at the same site (reinjury).There was a high prevalence of symptoms from injuries on the day of competition. This did not stop the team gymnasts from competing.
FRI0407 Relation of serum 25 oh vitamin d levels to disease activity in patients with systemic sclerosis
Authors: ö. I. Varol, H. T. özer, E. Nazlıcan, D. A. Taş, F. Yıldız
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is increasing evidence that Vitamin D has role in inflammatory processes in various diseases. Lower levels have been reported in rheumatoid arthritis, systemic lupus erythematosus and various other autoimmune disorders (1-3). <h3>Objectives</h3> The aim of the study is to investigate the relation of vitamin D status to the disease activity in patients with progressive systemic sclerosis (PSS), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). <h3>Methods</h3> Serum 25-0H-Vitamin D (Vit D) levels were measured in 62 PSS, 49 RA, 43 AS patients and 52 healthy study participants (HC). Disease activity was assessed using Valentini score, Disease Activity Score (DAS28), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) respectively. <h3>Results</h3> Serum Vit D levels were significantly lower (12.1+-8.6 ng/ml) in PSS than those of RA (18.6+-12.7 ng/ml), AS (22.6+-16.2 ng/ml) and healthy controls (19.5+-6.4 ng/ml), (P = 0.000). Significant correlations were found between Valentini scores and serum Vit D levels (r= -0.676, P = 0.000), between BASDAI and Vit D levels (r=-0.507, p=0.001); but not between DAS28 and Vit D levels(r= -0.246, p=0.088). A weak correlation was found between CRP and Vit D levels in RA group (r= -0.334, p=0.019). <h3>Conclusions</h3> Serum 25-OH-Vitamin D levels were significantly correlated with disease activity in PSS and AS. It may be due to immune modulatory effect of Vitamin D, or merely a result of the disease process or inflammation, i.e. a negative acute phase response. Further studies are needed to clarify its position in inflammation <h3>References</h3> Kostoglou-Athanassiou I, Athanassiou P, Lyraki A, Raftakis I, Antoniadis C. Vitamin D and rheumatoid arthritis. Ther Adv Endocrinol Metab. 2012 Dec;3(6):181-7. Muñoz-Ortego J, Torrente-Segarra V, Prieto-Alhambra D, Salman-Monte TC, Carbonell-Abello J. Prevalence and predictors of vitamin D deficiency in non-supplemented women with systemic lupus erythematosus in the Mediterranean region: a cohort study. Scand J Rheumatol. 2012;41(6):472-5. Agmon-Levin N, Theodor E, Segal RM, Shoenfeld Y. Vitamin D in Systemic and Organ-Specific Autoimmune Diseases. Clin Rev Allergy Immunol. 2012 Dec 14. [Epub ahead of print]. <h3>Disclosure of Interest</h3> None Declared
Activation of Myocardial Contraction by the N-Terminal Domains of Myosin Binding Protein-C
Authors: Todd J. Herron, Elena Rostkova, Gudrun Kunst, Rajiv Chaturvedi, Mathias Gautel, Jonathan C. Kentish
Journal: Circulation Research (2006)

Myosin binding protein-C (MyBP-C) is a poorly understood component of the thick filament in striated muscle sarcomeres. Its C terminus binds tightly to myosin, whereas the N terminus contains binding sites for myosin S2 and possibly for the thin filament. To study the role of the N-terminal domains of cardiac MyBP-C (cMyBP-C), we added human N-terminal peptide fragments to human and rodent skinned ventricular myocytes. At concentrations &gt;10 μmol/L, the N-terminal C0C2 peptide activated force production in the absence of calcium (pCa 9). Force at the optimal concentration (80 μmol/L) of C0C2 was ≈60% of that in maximal Ca 2+ (pCa 4.5), but the rate constant of tension redevelopment ( k tr ) matched or exceeded (by up to 80%) that produced by Ca 2+ alone. Experiments using different N-terminal peptides suggested that this activating effect of C0C2 resulted from binding by the pro/ala-rich C0-C1 linker region, rather than the terminal C0 domain. At a lower concentration (1 μmol/L), exogenous C0C2 strongly sensitized cardiac myofibrils to Ca 2+ at a sarcomere length (SL) of 1.9 μm but had no significant effect at SL 2.3 μm. This differential effect caused the normal SL dependence of myofibrillar Ca 2+ sensitivity to be reduced by 80% (mouse myocytes) or abolished (human myocytes) in 1 μmol/L C0C2. These results suggest that cMyBP-C provides a regulatory pathway by which the thick filament can influence the activation of the thin filament, separately from its regulation by Ca 2+ . Furthermore, the N-terminal region of cMyBP-C can influence the SL-tension (Frank–Starling) relationship in cardiac muscle.
Sleep-related hypoxaemia and excessive erythrocytosis in Andean high-altitude natives
Authors: L. Spicuzza, N. Casiraghi, A. Gamboa, C. Keyl, A. Schneider, A. Mori, F. Leon-Velarde, G.U. Di Maria, L. Bernardi
Journal: European Respiratory Journal (2003)

To determine whether nocturnal hypoxaemia contributes to the excessive erythrocytosis (EE) in Andean natives, standard polysomnographies were performed in 10 patients with EE and in 10 controls (mean haematocrit 76.6±1.3% and 54.4±0.8%, respectively) living at an altitude of 4,380 m. In addition, the effect of O 2 administration for 1 h prior to sleep, and the relationship between the hypoxic/hypercapnic ventilatory response and the apnoea/hypopnoea index (AHI) during sleep were studied. Awake arterial oxygen saturation ( S a,O 2 ) was significantly lower in patients with EEthan in controls (83.7±0.3% versus 85.6±0.4%). In both groups, the mean S a,O 2 significantly decreased during sleep (to 80.0±0.8% in EE and to 82.8±0.5% in controls). The mean S a,O 2 values remained significantly lower in patients with EE than in controls at all times of the night, and patients with EE spent significantly more time than the controls with an S a,O 2 of &lt;80%. There were no differences between the two groups in the number and duration of the apnoeas/hypopnoeas. None of these variables were affected by O 2 administration. In both groups the AHI positively correlated with the hypercapnic ventilatory response. Andean natives undergo minor respiratory disorders during sleep. The reduction inoxygen saturation found in subjects with excessive erythrocytosis was small, yet consistent and potentially important, as it remained below the threshold known for theincrease in erythropoietin stimulation. This may be an important factor promoting erythropoiesis, but its relevance needs to be further explored.
Ionizing Radiation Exposure to Patients Admitted With Acute Myocardial Infarction in the United States
Authors: Prashant Kaul, Sofia Medvedev, Samuel F. Hohmann, Pamela S. Douglas, Eric D. Peterson, Manesh R. Patel
Journal: Circulation (2010)

Background— Invasive and noninvasive cardiovascular imaging is beneficial in the care of patients admitted with acute myocardial infarction. Little is known about patients' cumulative radiation exposure. Methods and Results— All patients admitted with an acute myocardial infarction to any of 49 University HealthSystem Consortium member hospitals from 2006 to 2009 were reviewed for inpatient procedures involving ionizing radiation that included chest radiograph, computed tomogram scans, radionuclide imaging, diagnostic cardiac catheterization, and percutaneous coronary intervention. The average cumulative effective radiation dose per patient was estimated on the basis of published typical effective radiation doses for imaging procedures. Patients (n=64 071) admitted for acute myocardial infarction had a median age of 64.9 years. A total of 276 651 procedures involving ionizing radiation were performed during the study period, a median of 4.3 procedures per patient per admission. The majority of patients had invasive catheterization (77%), followed by computed tomogram scans (52%), mostly body examinations. The median cumulative effective radiation dose delivered was 15.02 mSv per patient per acute myocardial infarction admission. Postprocedural bleeding was a significant predictor of radiation exposure (odds ratio, 2.01; 95% confidence interval, 1.85 to 2.18), together with postprocedural mechanical complications resulting from device implantation (odds ratio, 2.86; 95% confidence interval, 2.61 to 3.13). Patients with higher underlying clinical complexity (defined by severity of illness scores) had higher radiation exposure and higher mortality ( P &lt;0.0001). There was also significant geographic variation in radiation exposure; patients in New England received the lowest cumulative exposure (odds ratio, 0.78; 95% confidence interval, 0.74 to 0.81). Conclusions— Acute myocardial infarction inpatients are exposed to an approximate median radiation dose of 15 mSv. This exposure is a result of multiple cardiovascular and noncardiovascular procedures. Efforts should be made to understand the risks and benefits of radiation exposure per episode of care for acute myocardial infarction.
Enrichment and expansion with nanoscale artificial antigen presenting cells for T cell adoptive immunotherapy
Authors: Karlo Perica, Joan Bieler, Christian Schuetz, Juan Varela, Mathias Oelke, Jonathan Schneck
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Adoptive T cell therapy can mediate durable regression of cancer [[1][1]]. While pre-existing anti-tumor responses can only be cultured from a minority of cancer patients [[2][2]], T cells specific for a wide variety of tumor antigens can be generated by stimulation of naive
A COMPARISON OF SIMULTANEOUS POLYGRAPH AND MICROGRAPH TRACINGS
Authors: Frank S. Meara, T. Homer Coffen, Albert C. Crehore
Journal: The Journal of Experimental Medicine (1912)

FROM A STUDY OF THE ACCOMPANYING TRACINGS WE MAY CONCLUDE THAT: 1. The delicate mechanism of the micrograph registers the movements in the heart and blood-vessels more accurately than does the polygraph. 2. The inertia of the polygraph lever and diaphragm distorts the tracing. The difference between the results obtained with the two instruments is shown by the records made simultaneously with the micrograph and the polygraph. 3. The micrograph is particularly useful for recording heart sounds. Some records illustrating this are shown. We are directing especial attention to this and will report the results in a subsequent paper. 4. While the micrograph will not supersede the polygraph or electrocardiograph, we feel that it has distinct possibilities as a clinical instrument.
A Survey of Chromosome Findings in 47 Cases of Bovine Lymphosarcoma (Leukemia)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W. C. D. Hare, Tsu-Ju Yang, R. A. McFeely
Journal: JNCI Journal of the National Cancer Institute (1967)

A survey has been made of chromosome studies on 47 histopathologically confirmed cases of bovine lymphosarcoma. Chromosome changes were found in 34 cases. Earlier observations that an inconstant pattern of chromosome changes occurs in this disease have been substantiated. The pattern of karyotypes observed was as follows: hypodiploid 1, diploid 5, hyperdiploid 25, and tetraploid or near tetraploid 8. In every animal in which more than one lymph node was analyzed, the same cell line(s) was found in each node. One of the X sex chromosomes was missing in 10 cases, and may have been missing in 2 others.
Effect of Low Frequency Vibration on the Arterial Wall
Authors: Derek R. Boughner, Margot R. Roach
Journal: Circulation Research (1971)

Poststenotic dilation is accompanied by alteration of the elastic properties of the arterial wall in the region where a murmur occurs. The low frequency vibrations contained in a murmur may cause the changes observed. Isolated human external iliac arteries were distended with 100 mm Hg pressure and vibrated with specific frequencies from 30 to 400 Hz. When dilation occurred, the radius increased at a rate of 7.1±3.4 SD % per day. However, for each artery, dilation tended to occur with one frequency in preference to others. The amplitude, as long as sufficient to produce vibration of the wall, was not important in determining this tendency. The older the artery the higher the frequency necessary to produce dilation. Young vessels, under 45 years, responded best to frequencies &lt;100 Hz, and vessels 45-60 years old responded to frequencies 100-200 Hz and older vessels, &gt;60 years, dilated with frequencies &gt;200 Hz. The elastic diagram of the vessel after dilation showed the major change to be in the elastin component of the arterial wall rather than the collagen. These findings correspond to those seen in a vessel displaying poststenotic dilation.