tbuckley/cabot-search huggingface dataset:
Age-Specific Differences in Oncogenic Pathway Dysregulation in Patients With Acute Myeloid Leukemia
Authors: Arati V. Rao, Peter J.M. Valk, Klaus H. Metzeler, Chaitanya R. Acharya, Sascha A. Tuchman, Marvaretta M. Stevenson, David A. Rizzieri, Ruud Delwel, Christian Buske, Stefan K. Bohlander, Anil Potti, Bob Löwenberg
Journal: Journal of Clinical Oncology (2009)

To define the biology driving the aggressive nature of acute myeloid leukemia (AML) in elderly patients.Clinically annotated microarray data from 425 patients with newly diagnosed de novo AML from two publicly available data sets were analyzed after age-specific cohorts (young <or= 45 years, n = 175; elderly >or= 55 years; n = 144) were prospectively identified. Gene expression analysis was conducted utilizing gene set enrichment analysis, and by applying previously defined and tested signature profiles reflecting dysregulation of oncogenic signaling pathways, altered tumor environment, and signatures of chemotherapy sensitivity.Elderly AML patients as expected had worse overall survival and event-free survival compared with younger patients. Analysis of oncogenic pathways revealed that older patients had higher probability of RAS, Src, and tumor necrosis factor (TNF) pathway activation (all P < .0001). Older patients were also less sensitive to anthracycline compared with younger patients with AML (P < .0001). Hierarchical clustering revealed that younger AML patients in cluster 2 had clinically worse survival, with high RAS, Src, and TNF pathway activation and in turn were less sensitive to anthracycline compared with patients in cluster 1. However, among elderly patients with AML, those in cluster 1 also demonstrated high RAS, Src, and TNF pathway activation but this did not translate into differences in survival or anthracycline sensitivity.AML in the elderly represents a distinct biologic entity characterized by unique patterns of deregulated signaling pathway variations that contributes to poor survival and anthracycline resistance. These insights should enable development and adjustments of clinically meaningful treatment strategies in the older patient population.
Insulin Glulisine Provides Improved Glycemic Control in Patients With Type 2 Diabetes
Authors: George Dailey, Julio Rosenstock, Robert G. Moses, Kirk Ways
Journal: Diabetes Care (2004)

OBJECTIVE—Insulin glulisine is a novel analog of human insulin designed for use as a rapid-acting insulin. This study compared the safety and efficacy of glulisine with regular human insulin (RHI) in combination with NPH insulin. RESEARCH DESIGN AND METHODS—In total, 876 relatively well-controlled patients with type 2 diabetes (mean HbA1c 7.55%) were randomized and treated with glulisine/NPH (n = 435) or RHI/NPH (n = 441) for up to 26 weeks in this randomized, multicenter, multinational, open-label, parallel-group study. Subjects were allowed to continue the same dose of prestudy regimens of oral antidiabetic agent (OAD) therapy (unless hypoglycemia necessitated a dose change). RESULTS—A slightly greater reduction from baseline to end point of HbA1c was seen in the glulisine group versus RHI (−0.46 vs. −0.30% with RHI; P = 0.0029). Also, at end point, lower postbreakfast (156 vs. 162 mg/dl [8.66 vs. 9.02 mmol/l]; P &amp;lt; 0.05) and postdinner (154 vs. 163 mg/dl [8.54 vs. 9.05 mmol/l]; P &amp;lt; 0.05) blood glucose levels were noted. Symptomatic hypoglycemia (overall, nocturnal, and severe) and weight gain were comparable between the two treatment groups. There were no between-group differences in baseline-to-end point changes in insulin dose. CONCLUSIONS—Twice-daily glulisine associated with NPH can provide small improvements in glycemic control compared with RHI in patients with type 2 diabetes who are already relatively well controlled on insulin alone or insulin plus OADs. The clinical relevance of such a difference remains to be established.
A Proposal for Reclassification of the Fuhrman Grading System in Patients with Clear Cell Renal Cell Carcinoma
Authors: Maxine Sun, Giovanni Lughezzani, Claudio Jeldres, Hendrik Isbarn, Shahrokh F. Shariat, Philippe Arjane, Hugues Widmer, Daniel Pharand, Mathieu Latour, Paul Perrotte, Jean-Jacques Patard, Pierre I. Karakiewicz
Journal: European Urology (2009)
MicroRNA-451 Exacerbates Lipotoxicity in Cardiac Myocytes and High-Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway
Authors: Yasuhide Kuwabara, Takahiro Horie, Osamu Baba, Shin Watanabe, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Tetsushi Nakao, Tomohiro Nishino, Kinya Otsu, Toru Kita, Takeshi Kimura, Koh Ono
Journal: Circulation Research (2014)

In some patients with type 2 diabetes mellitus (DM) without hypertension, cardiac hypertrophy and attenuated cardiac function are observed, and this insult is termed diabetic cardiomyopathy. To date, microRNA (miRNAs or miR) functions in diabetic cardiomyopathy remain to be elucidated.To clarify the functions of miRNAs involved in diabetic cardiomyopathy caused by type 2 DM.C57BL/6 mice were fed a high-fat diet (HFD) for 20 weeks, which induced obesity and type 2 DM. miRNA microarray analyses and real-time polymerase chain reaction revealed that miR-451 levels were significantly increased in the type 2 DM mouse hearts. Because excess supply of saturated fatty acids is a cause of diabetic cardiomyopathy, we stimulated neonatal rat cardiac myocytes with palmitic acid and confirmed that miR-451 expression was increased in a dose- and time-dependent manner. Loss of miR-451 function ameliorated palmitate-induced lipotoxicity in neonatal rat cardiac myocytes. Calcium-binding protein 39 (Cab39) is a scaffold protein of liver kinase B1 (LKB1), an upstream kinase of AMP-activated protein kinase (AMPK). Cab39 was a direct target of miR-451 in neonatal rat cardiac myocytes and Cab39 overexpression rescued the lipotoxicity. To clarify miR-451 functions in vivo, we generated cardiomyocyte-specific miR-451 knockout mice. HFD-induced cardiac hypertrophy and contractile reserves were ameliorated in cardiomyocyte-specific miR-451 knockout mice compared with control mice. Protein levels of Cab39 and phosphorylated AMPK were increased and phosphorylated mammalian target of rapamycin (mTOR) was reduced in cardiomyocyte-specific miR-451 knockout mouse hearts compared with control mouse hearts.Our results demonstrate that miR-451 is involved in diabetic cardiomyopathy through suppression of the LKB1/AMPK pathway.
Effects of a filter at the mouth on pulmonary function tests
Authors: L Fuso, D Accardo, G Bevignani, E Ferrante, A Della Corte, R Pistelli
Journal: European Respiratory Journal (1995)

The aim of this study was to verify whether the increase of resistance to airflow using a filter at the mouth could determine significant systematic errors of measurement or change the diagnostic performance in a respiratory physiology laboratory. The effect of the new filter Spirobac (DAR Spa, Italy) was assessed on out-patients referred to our laboratory for routine functional evaluation. The following tests were performed: maximal expiratory flow-volume curve, plethysmographic lung volume and airway resistance, bronchodilator test, and methacholine challenge test. Each test was performed randomly, twice with the filter and twice without. Significant differences between measurements with and without filter were found for forced vital capacity, forced expiratory volume in one second, airway resistance, and specific airway conductance (sGaw). These differences were unrelated to the average values of the measurements, except for sGaw. The limits of agreement were within the range of intraindividual short-term repeatability for almost all of the function indices. The overall concordance between tests performed with and without filter was 78% for bronchodilator test and 53% for methacholine test. However, in all the cases but one, the concordance of the methacholine test was inside the short-term repeatability. We conclude that the filter Spirobac has a statistically significant effect on the results of some pulmonary function tests. However, this is not considered to be clinically significant, since the changes due to the filter were within the intraindividual variability of repeated measurements for almost all the function indices and no appreciable classification error was found in diagnostic tests.
Three-dimensional potential gradient fields generated by intracardiac catheter and cutaneous patch electrodes.
Authors: A S Tang, P D Wolf, Y Afework, W M Smith, R E Ideker
Journal: Circulation (1992)

Defibrillation may be improved if electrode configurations can be found that create a larger and more even voltage gradient field across the heart. This study determined the magnitude of the shock gradient fields generated by four nonthoracotomy electrode configurations for defibrillation.In six dogs, a catheter was inserted containing a right ventricular apical electrode (V) and a right atrial electrode (A). A cutaneous patch electrode (P) was placed on the left lateral thorax. Shock potentials were recorded simultaneously from 128 electrodes in the left ventricular and right ventricular subepicardium and subendocardium, ventricular septum, and atria. With the chest closed, 50-mA shocks were given during diastole via the following lead configurations: V----A (V, cathode; A, anode); V----P; V----A+P; and V+A----P. Potential gradients were calculated at the subepicardium and subendocardium in millivolts per centimeter per volt of shock. In most dogs, the V----A+P configuration produced higher gradients throughout the ventricles than did V----A, V----P, or V+A----P. The maximum potential gradient was smaller for the V+A----P configuration than for V----A, V----P, or V----A+P. The gradient fields for the configurations with the catheter alone or combined with P were uneven.It is possible to estimate shock gradient fields in three dimensions. Of the four configurations tested, V----A+P produced the highest gradients and V+A----P produced the lowest high gradient. The gradient fields were uneven throughout the ventricles.
Methylation-Dependent Gene Silencing Induced by Interleukin 1β via Nitric Oxide Production
Authors: Abdelkrim Hmadcha, Francisco J. Bedoya, Francisco Sobrino, Elizabeth Pintado
Journal: The Journal of Experimental Medicine (1999)

Interleukin (IL)-1β is a pleiotropic cytokine implicated in a variety of activities, including damage of insulin-producing cells, brain injury, or neuromodulatory responses. Many of these effects are mediated by nitric oxide (NO) produced by the induction of NO synthase (iNOS) expression. We report here that IL-1β provokes a marked repression of genes, such as fragile X mental retardation 1 (FMR1) and hypoxanthine phosphoribosyltransferase (HPRT), having a CpG island in their promoter region. This effect can be fully prevented by iNOS inhibitors and is dependent on DNA methylation. NO donors also cause FMR1 and HPRT gene silencing. NO-induced methylation of FMR1 CpG island can be reverted by demethylating agents which, in turn, produce the recovery of gene expression. The effects of IL-1β and NO appear to be exerted through activation of DNA methyltransferase (DNA MeTase). Although exposure of the cells to NO does not increase DNA MeTase gene expression, the activity of the enzyme selectively increases when NO is applied directly on a nuclear protein extract. These findings reveal a previously unknown effect of IL-1β and NO on gene expression, and demonstrate a novel pathway for gene silencing based on activation of DNA MeTase by NO and acute modification of CpG island methylation.
Predictors of Self-Neglect in Community-Dwelling Elders
Authors: Robert C Abrams, Mark Lachs, Gail McAvay, Denis J Keohane, Martha L Bruce
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The study assessed the contribution of depressive symptoms and cognitive impairment to the prediction of self-neglect in elderly persons living in the community. METHOD: Data were drawn from the New Haven Established Populations for Epidemiologic Studies of the Elderly cohort, which included 2,812 community residents age 65 years and older in 1982. The principal outcome examined was the incidence of self-neglect, corroborated by the state’s investigation, during 9 years of follow-up (1982–1991). RESULTS: Among the 2,161 subjects included in the analysis, 92 corroborated cases of self-neglect occurred from 1982 to 1991. The prevalence of clinically significant depressive symptoms at baseline (score ≥16 on the Center for Epidemiologic Studies Depression Scale [CES-D]) was 15.4%, and the prevalence of clinically significant cognitive impairment (four or more errors on the Pfeiffer Short Portable Mental Status Questionnaire) was 7.5%. Subjects with clinically significant depressive symptoms and/or cognitive impairment were more likely than others to experience self-neglect. Clinically significant depressive symptoms and cognitive impairment remained significant predictors of self-neglect in a multivariate model that included age, gender, race, and income. A final model for self-neglect constructed with stepwise selection of risk factors included depressive symptoms and cognitive impairment, as well as male gender, older age, income less than $5,000 per year, living alone, history of hip fracture, and history of stroke. CONCLUSIONS: Elderly individuals living in the community who experience clinically significant depressive symptoms and/or cognitive impairment may be at risk for the development of self-neglect and may become candidates for intervention.
Acute Respiratory Tract Infections and Mannose-Binding Lectin Insufficiency During Early Childhood
Authors: A Koch, M Melbye, P Sørensen, P Homøe, H O Madsen, K Mølbak, C H Hansen, L H Andersen, G W Hahn, P Garred
Journal: JAMA (2001)

ContextHospital-based studies have found that increased susceptibility to certain infections is associated with low serum levels of mannose-binding lectin (MBL) due to MBL variant alleles. However, the contribution of MBL insufficiency to incidence of common childhood infections at a population level is unknown.ObjectiveTo investigate the effect of MBL insufficiency on risk for acute respiratory tract infection (ARI) in unselected children younger than 2 years.Design and SettingPopulation-based, prospective, cohort study conducted in Sisimiut, Greenland.ParticipantsTwo hundred fifty-two children younger than 2 years who were followed up weekly between August 1996 and August 1998 for morbidity surveillance.Main Outcome MeasureRisk of ARI, based on medical history and clinical examination, compared by MBL genotype, determined from blood samples based on presence of structural and promoter alleles.ResultsA 2.08-fold (95% confidence interval [CI], 1.41-3.06) increased relative risk (RR) of ARI was found in MBL-insufficient children (n = 13) compared with MBL-sufficient children (n = 239; P&lt;.001). The risk association was largely restricted to children aged 6 to 17 months (RR, 2.92; 95% CI, 1.78-4.79) while less effect (RR, 1.47; 95% CI, 0.45-4.82) and no effect (RR, 1.00; 95% CI, 0.42-2.37) was shown among children aged 0 to 5 months and 18 to 23 months, respectively.ConclusionThese data suggest that genetic factors such as MBL insufficiency play an important role in host defense, particularly during the vulnerable period of childhood from age 6 through 17 months, when the adaptive immune system is immature.
Long-range base pairing in Drosophila and human mRNA sequences
Authors: J. Parsch, W. Stephan, S. Tanda
Journal: Molecular Biology and Evolution (1998)

The potential for long-range base pairing between the 5' and 3' ends of mRNA molecules was examined for 134 Drosophila and 204 human sequences collected from the GenBank database. Each sequence was divided into two parts, a 5' sequence taken from the start of the protein-encoding region and a 3' sequence taken from the end of the transcript. The strongest RNA pairing stem between each pair of 5' and 3' sequences was identified and scored using an alignment program modified to incorporate RNA base pairing. The observed pairing scores were then compared with a random distribution of scores generated by aligning each 5' sequence to random permutations of its corresponding 3' sequence. For both the Drosophila and the human mRNAs, the observed pairing scores were significantly biased toward the upper tail of the random distributions, with 61% of the Drosophila sequences and 64% of the human sequences falling within the upper half of the random distributions. This suggests that a pattern of long-range base pairing may be a common feature of eukaryotic mRNAs. We have also analyzed a subset of Drosophila and human mRNAs which show the greatest potential for long-range pairing. The human pairings appear to be stronger and localized to more specific regions near the ends of the mRNA sequence than those of Drosophila.
Simultaneous Comparison of Antegrade and Collateral Coronary Blood Flows
Authors: LAURO B. DE VERA, HERBERT GOLD, ELIOT CORDAY
Journal: Circulation Research (1958)

Comparison of the antegrade and retrograde (collateal) coronary free flows showed that the retrograde flow was less than 10 per cent of the antegrade flow in 48 per cent of animals and above 20 per cent in 11 per cent of animals.
Adjuvant trastuzumab cardiotoxicity in patients over 60 years of age with early breast cancer: a multicenter cohort analysis
Authors: L. Tarantini, S. Gori, P. Faggiano, G. Pulignano, E. Simoncini, F. Tuccia, R. Ceccherini, D. Bovelli, C. Lestuzzi, G. Cioffi
Journal: Annals of Oncology (2012)
Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats
Authors: İlker Öngüç Aycan, Adnan Tüfek, Orhan Tokgöz, Osman Evliyaoğlu, Uğur Fırat, Gönül Ölmez Kavak, Hüseyin Turgut, Mustafa Uğur Yüksel
Journal: International Journal of Surgery (2014)
RELEASE OF CHYMOTRYPSIN‐LIKE ESTERASE FROM ISOLATED RAT PERITONEAL MAST CELLS BY ARGININE‐RICH CALF THYMUS HISTONE
Authors: SATOSHI DEKIO, HIROSHI ISHIHARA, TAKUSO YAMURA
Journal: Allergy (1976)

Release of chymotrypsin-like esterase from isolated rat peritoneal mast cells by arginine-rich and lysine-rich calf thymus histones was investigated. The arginine-rich histone released the esterase, but the lysine-rich histone did not release the esterase from the mast cells. The isolated mast cells spontaneously released the esterase gradually. The chymotrypsin-like esterase released from the mast cells is considered to digest the destructed material in tissues in a state of chronic destruction, such as chronically inflamed tissues and malignant tumours.
Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis
Authors: Gerald B. Appel, Gabriel Contreras, Mary Anne Dooley, Ellen M. Ginzler, David Isenberg, David Jayne, Lei-Shi Li, Eduardo Mysler, Jorge Sa[Combining Acute Accent]nchez-Guerrero, Neil Solomons, David Wofsy
Journal: Journal of the American Society of Nephrology (2009)

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
Modeling Supravalvular Aortic Stenosis Syndrome With Human Induced Pluripotent Stem Cells
Authors: Xin Ge, Yongming Ren, Oscar Bartulos, Min Young Lee, Zhichao Yue, Kun-Yong Kim, Wei Li, Peter J. Amos, Esra Cagavi Bozkulak, Amulya Iyer, Wei Zheng, Hongyu Zhao, Kathleen A. Martin, Darrell N. Kotton, George Tellides, In-Hyun Park, Lixia Yue, Yibing Qyang
Journal: Circulation (2012)

Supravalvular aortic stenosis (SVAS) is caused by mutations in the elastin (ELN) gene and is characterized by abnormal proliferation of vascular smooth muscle cells (SMCs) that can lead to narrowing or blockage of the ascending aorta and other arterial vessels. Having patient-specific SMCs available may facilitate the study of disease mechanisms and development of novel therapeutic interventions.Here, we report the development of a human induced pluripotent stem cell (iPSC) line from a patient with SVAS caused by the premature termination in exon 10 of the ELN gene resulting from an exon 9 four-nucleotide insertion. We showed that SVAS iPSC-derived SMCs (iPSC-SMCs) had significantly fewer organized networks of smooth muscle α-actin filament bundles, a hallmark of mature contractile SMCs, compared with control iPSC-SMCs. The addition of elastin recombinant protein or enhancement of small GTPase RhoA signaling was able to rescue the formation of smooth muscle α-actin filament bundles in SVAS iPSC-SMCs. Cell counts and BrdU analysis revealed a significantly higher proliferation rate in SVAS iPSC-SMCs than control iPSC-SMCs. Furthermore, SVAS iPSC-SMCs migrated at a markedly higher rate to the chemotactic agent platelet-derived growth factor compared with the control iPSC-SMCs. We also provided evidence that elevated activity of extracellular signal-regulated kinase 1/2 is required for hyperproliferation of SVAS iPSC-SMCs. The phenotype was confirmed in iPSC-SMCs generated from a patient with deletion of elastin owing to Williams-Beuren syndrome.SVAS iPSC-SMCs recapitulate key pathological features of patients with SVAS and may provide a promising strategy to study disease mechanisms and to develop novel therapies.
Universals of reading: Developmental evidence for linguistic plausibility
Authors: Usha Goswami
Journal: Behavioral and Brain Sciences (2012)

Abstract Children's reading and spelling errors show that orthographic learning involves complex interactions with phonology, morphology, and meaning throughout development. Even young children seek to make their visual word recognition strategies linguistically coherent. Orthographic knowledge gained through spelling affects reading, and vice versa. Developmental data support Frost's claim that letter-coding flexibility reflects the optimization of encoding resources in a highly developed system.
NEUTROPHIL DYSFUNCTION, CHRONIC GRANULOMATOUS DISEASE, AND NON-SPHEROCYTIC HÆMOLYTIC ANÆMIA CAUSED BY COMPLETE DEFICIENCY OF GLUCOSE-6-PHOSPHATE DEHYDROGENASE
Authors: G.R. Gray, G. Stamatoyannopoulos, S.C. Naiman, M.R. Kliman, S.J. Klebanoff, T. Austin, A. Yoshida, G.C.F. Robinson
Journal: The Lancet (1973)