tbuckley/cabot-search huggingface dataset:
Age- and Sex-Specific Incidence of Childhood Leukemia by Immunophenotype in the Nordic Countries
Authors: Lisa Lyngsie Hjalgrim, Klaus Rostgaard, Kjeld Schmiegelow, Stefan Söderhäll, Svein Kolmannskog, Kim Vettenranta, Jon Kristinsson, Niels Clausen, Mads Melbye, Henrik Hjalgrim, Göran Gustafsson
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Studies from various countries have found an increasing incidence of childhood leukemia in recent decades. To characterize time trends in the age- and sex-specific incidence of childhood acute leukemia during the last 20 years in the Nordic countries, we analyzed a large set of population-based data from the Nordic Society of Paediatric Haematology and Oncology (NOPHO) in their acute leukemia database covering a population of approximately 5 million children aged 0–14 years. Methods: Temporal trends in acute myeloid leukemia and acute lymphoblastic leukemia incidence rates overall and for acute lymphoblastic leukemia immunophenotypes and for specific age groups were analyzed by Poisson regression adjusting for age, sex, and country. All statistical tests were two-sided. Results: We identified 1595 girls and 1859 boys diagnosed with acute lymphoblastic leukemia between January 1, 1982, and December 31, 2001, and 260 girls and 224 boys diagnosed with de novo acute myeloid leukemia between January 1, 1985, and December 31, 2001. No statistically significant change was seen in the overall incidence rate for acute lymphoblastic leukemia during the 20-year study (annual change = 0.22%, 95% confidence interval [CI] = −0.36% to 0.80%). The incidence rate of B-precursor acute lymphoblastic leukemia remained unchanged (annual change = 0.30%, 95% CI = −0.57% to 1.18%) from January 1, 1986, through December 31, 2001. A somewhat lower incidence in the first years of the study period indicated an early increasing incidence of B-precursor acute lymphoblastic leukemia that corresponded to a simultaneous decreasing incidence of unclassified acute lymphoblastic leukemia. Incidences of T-cell acute lymphoblastic leukemia (annual change = 1.55%, 95% CI = −1.14% to 4.31%) and acute myeloid leukemia (annual change = 0.58%, 95% CI = −1.24% to 2.44%) were stable during the study period. Conclusion: Incidences of acute myeloid leukemia overall, acute lymphoblastic leukemia overall, and specific acute lymphoblastic leukemia immunophenotypes have been stable in the Nordic countries over the past two decades.
PET imaging of brain macrophages using the peripheral benzodiazepine receptor in a macaque model of neuroAIDS
Authors: Sriram Venneti, Brian J Lopresti, Guoji Wang, Stephanie J Bissel, Chester A Mathis, Carolyn C Meltzer, Fernando Boada, Saverio Capuano, Geraldine J Kress, Denise K Davis, James Ruszkiewicz, Ian J Reynolds, Michael Murphey-Corb, Anita M Trichel, Stephen R Wisniewski, Clayton A Wiley
Journal: Journal of Clinical Investigation (2004)

HIV infection in humans and simian immunodeficiency virus (SIV) infection in macaques result in encephalitis in approximately one-quarter of infected individuals and is characterized by infiltration of the brain with infected and activated macrophages. 1-(2-chlorphenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (PK11195) is a ligand specific for the peripheral benzodiazepine receptor abundant on macrophages and is expressed in low levels in the noninfected brain. We hypothesized that positron-emission tomography (PET) with the carbon-11–labeled, R-enantiomer form of PK11195 ([11C](R)-PK11195) could image brain macrophages and hence the development of encephalitis in vivo. [11C](R)-PK11195 binding was assessed in the brain using PET in 11 SIV infected macaques, six of which showed increased binding in vivo. Postmortem examination of the brain in these six macaques demonstrated encephalitis, while macaques that did not show an increase in [11C](R)-PK11195 binding did not develop SIV encephalitis. Brain tissue from SIV encephalitic macaques also showed increased [3H](R)-PK11195 binding compared with binding in nonencephalitic macaques. Increased PK11195 binding in vivo and in postmortem brain tissue correlated with abundance of macrophages but not astrocytes. Our results suggest that PET [11C](R)-PK11195 imaging can detect the presence of macrophages in SIV encephalitis in vivo and may be useful to predict the development of HIV encephalitis and in studies of the pathogenesis and treatment of HIV dementia.
Randomized Active-Controlled Phase II Study of Denosumab Efficacy and Safety in Patients With Breast Cancer-Related Bone Metastases
Authors: Allan Lipton, Guenther G. Steger, Jazmin Figueroa, Cristina Alvarado, Philippe Solal-Celigny, Jean-Jacques Body, Richard de Boer, Rossana Berardi, Pere Gascon, Katia S. Tonkin, Robert Coleman, Alexander H.G. Paterson, Mark C. Peterson, Michelle Fan, Amy Kinsey, Susie Jun
Journal: Journal of Clinical Oncology (2007)

Purpose Denosumab, a fully human monoclonal antibody to receptor activator of nuclear factor-κB ligand, suppresses bone resorption. In this study, we evaluated the efficacy and safety of five dosing regimens of denosumab in patients with breast cancer-related bone metastases not previously treated with intravenous bisphosphonates (IV BPs). Patients and Methods Eligible women (n = 255) with breast cancer-related bone metastases were stratified by type of antineoplastic therapy received and randomly assigned to one of six cohorts (five denosumab cohorts [blinded to dose and frequency]; one open-label IV BP cohort). Denosumab was administered subcutaneously every 4 weeks (30, 120, or 180 mg) or every 12 weeks (60 or 180 mg). The primary end point was percentage of change in the bone turnover marker urine N-telopeptide corrected for urine creatinine (uNTx/Cr) from baseline to study week 13. The percentage of patients achieving more than 65% uNTx/Cr reduction, time to more than 65% uNTx/Cr reduction, patients experiencing one or more on-study skeletal-related events (SRE), and safety were also evaluated. Results At study week 13, the median percent reduction in uNTx/Cr was 71% for the pooled denosumab groups and 79% for the IV BP group. Overall, 74% of denosumab-treated patients (157 of 211) achieved a more than 65% reduction in uNTx/Cr compared with 63% of bisphosphonate-treated patients (27 of 43). On-study SREs were experienced by 9% of denosumab-treated patients (20 of 211) versus 16% of bisphosphonate-treated patients (seven of 43). No serious or fatal adverse events related to denosumab occurred. Conclusion Subcutaneous denosumab may be similar to IV BPs in suppressing bone turnover and reducing SRE risk. The safety profile was consistent with an advanced breast cancer population receiving systemic therapy.
Obama reverses US federal funding restrictions on stem cell research
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

President Barack Obama has removed the ban introduced by the previous US president, George Bush, on using federal funds to support embryonic stem cell research, in an executive order issued this week.

Government support will now be available for research with many more stem cell lines than previously. These lines are developed from surplus embryos that remain after fertility treatment; the embryos would otherwise have been stored indefinitely or destroyed.

President Obama said that human cloning would never be permitted and that research would proceed under strict guidelines to be developed by the National Institutes of Health over the next four months.

The order does not provide …
Nucleotide Variation of the Duplicated Amylase Genes in Drosophila kikkawai
Authors: Nobuyuki Inomata, Tsuneyuki Yamazaki
Journal: Molecular Biology and Evolution (2002)

We examined levels and patterns of the nucleotide polymorphism of the Amylase genes with a head-to-head duplication in Drosophila kikkawai. The levels of variation in D. kikkawai were comparable to those in Drosophila melanogaster. Tajima's test, Fu and Li's test, HKA test, and MK test did not show significant departure from neutrality. We found an excess of replacement changes in the within-locus class, representing polymorphism in one of the duplicated genes, compared with the between-locus class, representing polymorphism shared between the duplicated genes. Most replacement changes in the within-locus class were singletons. These results suggest that most replacement changes are deleterious. A contrasting evolutionary pattern, involving concerted evolution in the coding regions but differential evolution in the 5′-flanking regions, was observed. However, unlike the duplicated Amy genes of D. melanogaster, the coding regions of the duplicated genes in D. kikkawai tended to diverge. Using Ohta's model of the small multigene family, we found that recombination (interchromosomal equal crossing-over) rate was one order higher than gene conversion (unequal crossing-over) rate, resulting in a considerable but incomplete homogenization of the duplicated coding regions. Linkage disequilibria were found in the intron as well as within and around the regulatory cis-element sequences of one of the duplicated genes (Amy1). The possible causes of these linkage disequilibria were discussed.
Severe hereditary spherocytosis and distal renal tubular acidosis associated with the total absence of band 3
Authors: Maria Letı́cia Ribeiro, Nicole Alloisio, Helena Almeida, Clara Gomes, Pascale Texier, Carlos Lemos, Gabriela Mimoso, Laurette Morlé, Faı̈za Bey-Cabet, René-Charles Rudigoz, Jean Delaunay, Gabriel Tamagnini
Journal: Blood (2000)
A combination of erythromycin and dexamethasone reduces inflammatory effects of exposure to cigarette smoke extract through modulation of Akt and histone deacetylase 2
Authors: Xuejiao Sun, Xiaoning Zhong, Zhiyi He, Zhanhua Li, Yang Zhang, Guang Zhou, Jiangquan Zhang
Journal: European Respiratory Journal (2014)

While erythromycin (EM) has been shown to play an anti-inflammatory role in COPD, it is unclear whether a combination of EM and corticosteroid would further reduce inflammatory effects. Here, we determined the molecular mechanisms by which combination therapy may repress inflammatory gene expression in monocytes. We demonstrated that combination treatment inhibited release of IL-8 in PBMCs of COPD patients and U937 exposed to CSE.  The CSE-induce reduction in HDAC2 protein could be reversed by combination treatment.  CSE increased PAkt expression in a concentration-dependent manner. PAkt expression could be reversed by EM in a dose-dependent manner. Our results verify that combination treatment of U937 cells prior to CSE exposure increases protein levels of HDAC2 and reduces PAkt levels. Combination therapy of EM and corticosteroid may be an effective therapy in the treatment of COPD.
A structured training programme for caregivers of inpatients after stroke (TRACS): a cluster randomised controlled trial and cost-effectiveness analysis
Authors: Anne Forster, Josie Dickerson, John Young, Anita Patel, Lalit Kalra, Jane Nixon, David Smithard, Martin Knapp, Ivana Holloway, Shamaila Anwar, Amanda Farrin
Journal: The Lancet (2013)
β 2 adrenergic receptor variant lle164: effect on heart failure survival and impact of beta blockade
Authors: Dana S. Mahlab, Lisa A. Postava, Richard Holubkov, Joseph Shilkofski, Guy A. MacGowan, Michael A. Mathier, Srinivas Murali, Karen Janosko, Arthur M. Feldman, Barry London, Dennis M. McNamara
Journal: Journal of the American College of Cardiology (2002)
Identification of Cancer Stem Cell–Like Side Population Cells in Human Nasopharyngeal Carcinoma Cell Line
Authors: Jing Wang, Li-Ping Guo, Li-Zhen Chen, Yi-Xin Zeng, Shih Hsin Lu
Journal: Cancer Research (2007)

Abstract Side population (SP) cells have been isolated from several solid tumors. They lack distinct molecular markers for cancer stem cells (CSC) and increasing evidence suggests that they may play an important role in tumorigenesis and cancer therapy. However, there are no reports about the existence and function of SP cells in nasopharyngeal carcinoma (NPC) cells thus far. In this study, we scanned SP cells from five NPC cell lines and investigated stem cell characteristics, such as proliferation, self-renewal, and differentiation, using SP cells from the widely-used CNE-2 NPC cell line. We observed a strong tumorigenesis ability of SP cells following in vivo transplantation into nonobese diabetic/severe combined immunodeficient mice. Immunofluorescence revealed that cytokine 19 was highly expressed on SP cells. SP cells were found to be more resistant to chemotherapy and radiotherapy and this was related to the ATP-binding cassette half transporter member 2 of G family protein and Smoothened protein expression, respectively. Our results not only showed that SP cells in human NPC cell line CNE-2 had stem cell characteristics in vitro but also showed that they had a strong ability to form tumors in vivo. Importantly, we found the cell marker, cytokine 19, may serve as a potential molecular marker for further characterization of CSC. Taken together, our data shed light on tumorigenesis and therapeutic-resistant mechanisms, which are helpful for developing novel targets for effective clinical treatment of NPC. [Cancer Res 2007;67(8):3716–24]
Management of Hot Flashes in Patients Who Have Breast Cancer With Venlafaxine and Clonidine: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Annelies H. Boekhout, Andrew D. Vincent, Otilia B. Dalesio, Joan van den Bosch, Joke H. Foekema-Töns, Sandra Adriaansz, Sylvia Sprangers, Bastiaan Nuijen, Jos H. Beijnen, Jan H.M. Schellens
Journal: Journal of Clinical Oncology (2011)

Purpose Therapies for breast cancer may induce hot flashes that can affect quality of life. We undertook a double-blind, placebo-controlled trial with the primary objective of comparing the average daily hot flash scores in the twelfth week among patients treated with venlafaxine, clonidine, and placebo. Additional analyses of the hot flash score over the full 12 weeks of treatment were performed. Patients and Methods In all, 102 patients with a history of breast cancer were randomly assigned (2:2:1) to venlafaxine 75 mg, clonidine 0.1 mg, or placebo daily for 12 weeks. Questionnaires at baseline and during treatment assessed daily hot flash scores, sexual function, sleep quality, anxiety, and depression. Results After 12 weeks, a total of 80 patients were evaluable for the primary end point. During week 12, hot flash scores were significantly lower in the clonidine group versus placebo (P = .03); for venlafaxine versus placebo, the difference was borderline not significant (P = .07). However, hot flash scores were equal in the clonidine and venlafaxine groups. Over the course of 12 weeks, the differences between both treatments and placebo were significant (P &lt;.001 for venlafaxine v placebo; P = .045 for clonidine v placebo). Frequencies of treatment-related adverse effects of nausea (P = .02), constipation (P = .04), and severe appetite loss were higher in the venlafaxine group. Conclusion Venlafaxine and clonidine are effective treatments in the management of hot flashes in patients with breast cancer. Venlafaxine resulted in a more immediate reduction of hot flash scores when compared with clonidine; however, hot flash scores at week 12 were lower in the clonidine group than in the venlafaxine group.
The changes in airways structure associated with reduced forced expiratory volume in one second
Authors: K Matsuba, JL Wright, BR Wiggs, PD Pare, JC Hogg
Journal: European Respiratory Journal (1989)

We compared the structure of the membranous and respiratory bronchioles of resected lungs from 111 patients with a normal predicted forced expiratory volume in one second (FEV1) to the structure of these airways from 45 patients with an FEV1 reduced below the 95% confidence limits for height and age. Membranous and respiratory bronchioles of less than 2 mm in internal diameter were counted and their diameter and wall thickness were measured. The data show that there were more membranous bronchioles of internal diameter less than 0.4 mm in patients with reduced FEV1. The wall thickness of respiratory bronchioles was increased in the obstructed group and there was also an increase in the ratio of wall thickness to lumen diameter in these airways. The walls of membranous bronchioles were not increased in thickness but there was an increase in the ratio of wall thickness to lumen diameter. Although the data is consistent with the hypothesis that airways obstruction in patients with chronic obstructive pulmonary disease is due to thickening of the airway wall and narrowing of the airway lumen, we cannot rule out distortion of the membranous bronchioles by loss of elastic recoil.
Influence of polymyxin B, a probe for anionic phospholipids, on calcium binding and calcium and potassium fluxes of cultured cardiac cells.
Authors: J M Burt, C J Duenas, G A Langer
Journal: Circulation Research (1983)

Polymyxin B, an amphiphilic, cationic peptidolipid, which is thought to bind to anionic phospholipids in cell membranes, is shown to interact with the cellular calcium of cultured neonatal rat myocardial cells in a dose-dependent, partially reversible manner. At concentrations of less than or equal to 0.1 mM, it has two distinct effects. First, it results in displacement of 1.4 +/- 0.3 mmol Ca/kg dry weight, which is equivalent to 18.1 +/- 3.4% of the total exchangeable cellular calcium. Total calcium displaced by polymyxin B and a nonspecific cationic probe, lanthanum, at its maximal displacing concentration (1 mM), was 5.9 +/- 1.3 mmol/kg dry weight. Thus, the total displaceable calcium represented 76.3 +/- 2.5% of the total exchangeable calcium. Second, polymyxin B (less than or equal to 0.1 mM) causes a reduction in net uptake of calcium, and slows the efflux of both calcium and potassium. Concentrations of polymyxin B higher than 0.1 mM result in an initial displacement of calcium, followed by an irreversible and sustained period of enhanced net calcium uptake. Efflux of calcium is slowed at the higher polymyxin B concentrations, whereas efflux of potassium is enhanced. Cellular contractile activity and electrical activity are irreversibly altered only by the higher concentrations. The results suggest that polymyxin B is a useful probe for the role of membrane phospholipids in control of ion binding and fluxes.
The Rectal Cancer microRNAome – microRNA Expression in Rectal Cancer and Matched Normal Mucosa
Authors: Jochen Gaedcke, Marian Grade, Jordi Camps, Rolf Søkilde, Bogumil Kaczkowski, Aaron J. Schetter, Michael J. Difilippantonio, Curtis C. Harris, B. Michael Ghadimi, Søren Møller, Tim Beissbarth, Thomas Ried, Thomas Litman
Journal: Clinical Cancer Research (2012)

miRNAs play a prominent role in a variety of physiologic and pathologic biologic processes, including cancer. For rectal cancers, only limited data are available on miRNA expression profiles, whereas the underlying genomic and transcriptomic aberrations have been firmly established. We therefore, aimed to comprehensively map the miRNA expression patterns of this disease.Tumor biopsies and corresponding matched mucosa samples were prospectively collected from 57 patients with locally advanced rectal cancers. Total RNA was extracted, and tumor and mucosa miRNA expression profiles were subsequently established for all patients. The expression of selected miRNAs was validated using semi-quantitative real-time PCR.Forty-nine miRNAs were significantly differentially expressed (log(2)-fold difference >0.5 and P < 0.001) between rectal cancer and normal rectal mucosa. The predicted targets for these miRNAs were enriched for the following pathways: Wnt, TGF-beta, mTOR, insulin, mitogen-activated protein kinase, and ErbB signaling. Thirteen of these 49 miRNAs seem to be rectal cancer-specific, and have not been previously reported for colon cancers: miR-492, miR-542-5p, miR-584, miR-483-5p, miR-144, miR-2110, miR-652, miR-375, miR-147b, miR-148a, miR-190, miR-26a/b, and miR-338-3p. Of clinical impact, miR-135b expression correlated significantly with disease-free and cancer-specific survival in an independent multicenter cohort of 116 patients.This comprehensive analysis of the rectal cancer miRNAome uncovered novel miRNAs and pathways associated with rectal cancer. This information contributes to a detailed view of this disease. Moreover, the identification and validation of miR-135b may help to identify novel molecular targets and pathways for therapeutic exploitation.
Obesity, Inactivity, and the Prevalence of Diabetes and Diabetes-Related Cardiovascular Comorbidities in the U.S., 2000–2002
Authors: Patrick W. Sullivan, Elaine H. Morrato, Vahram Ghushchyan, Holly R. Wyatt, James O. Hill
Journal: Diabetes Care (2005)

Obesity and physical inactivity are established risk factors for type 2 diabetes and cardiovascular comorbidities. Whether adiposity or fitness level is more important to health is controversial. The objective of this research is to determine the relative associations of physical activity and BMI with the prevalence of diabetes and diabetes-related cardiovascular comorbidities in the U.S.The Medical Expenditure Panel Survey (MEPS) is a nationally representative survey of the U.S. population. From 2000 to 2002, detailed information on sociodemographic characteristics and health conditions were collected for 68,500 adults. Normal weight was defined as BMI 18.5 to <25 kg/m(2), overweight 25 to < or =30 kg/m(2), obese (class I and II) 30 to <40 kg/m(2), and obese (class III) > or =40 kg/m(2). Physical activity was defined as moderate/vigorous activity > or =30 min > or =3 days per week.The likelihood of having diabetes and diabetes-related cardiovascular comorbidities increased with BMI regardless of physical activity and increased with physical inactivity regardless of BMI. Compared with normal-weight active adults, the multivariate-adjusted odds ratio (OR) for diabetes was 1.52 (95% CI 1.25-1.86) for normal-weight inactive adults and 1.65 (1.40-1.96) for overweight inactive adults; the OR for diabetes and comorbid hypertension was 1.71 (1.32-2.19) for normal-weight inactive adults and 1.84 (1.47-2.32) for overweight inactive adults.Both physical inactivity and obesity seem to be strongly and independently associated with diabetes and diabetes-related comorbidities. These results support continued research investigating the independent causal nature of these factors.