tbuckley/cabot-search huggingface dataset:
The Partnership Access Line
Authors: Robert J Hilt, Melissa A Romaire, Michael G McDonell, Jeanne M Sears, Antoinette Krupski, Jeffery N Thompson, Jim Myers, Eric W Trupin
Journal: JAMA Pediatrics (2012)

<h3>Objective</h3>To evaluate a telephone-based child mental health consult service for primary care providers (PCPs).<h3>Design</h3>Record review, provider surveys, and Medicaid database analysis.<h3>Setting</h3>Washington State Partnership Access Line (PAL) program.<h3>Participants</h3>A total of 2285 PAL consultations by 592 PCPs between April 1, 2008, and April 30, 2011.<h3>Interventions</h3>Primary care provider–initiated consultations with PAL service.<h3>Main Outcome Measures</h3>The PAL call characteristics, PCP feedback surveys, and Medicaid claims between April 2007 and December 2009 for fee-for-service Medicaid children before and after a PAL call.<h3>Results</h3>Sixty-nine percent of calls were about children with serious emotional disturbances, and 66% of calls were about children taking psychiatric medications. Primary care providers nearly always received new psychosocial treatment advice (87% of calls) and were more likely to receive advice to start rather than stop a medication (46% vs 24% of calls). Primary care provider feedback surveys reported uniformly positive satisfaction with the program. Among Medicaid children, there was significant increases in attention-deficit/hyperactivity disorder and antidepressant medication use after the PAL call but no significant change in reimbursements for mental health medications (P &lt; .05). Children with a history of foster care experienced a 132% increase in outpatient mental health visits after the PAL call (P &lt; .05).<h3>Conclusions</h3>Primary care providers used PAL for psychosocial and medication treatment assistance for particularly high-needs children and were satisfied with the service. Furthermore, PAL was associated with increased use of outpatient mental health care for some children.
Comparison between a new once-daily, bronchodilating drug, bambuterol, and terbutaline sustained-release, twice daily
Authors: G Persson, Y Gnosspelius, S Anehus
Journal: European Respiratory Journal (1988)

Bambuterol is a prodrug, from which terbutaline is slowly generated. The objectives of the study were to evaluate whether bambuterol, given once daily, can control symptoms in asthmatic patients and to compare the bronchodilating effect and the side effects with those of terbutaline sustained-release (SR) tablets given twice daily. Twenty-five out-patients with bronchial asthma were treated during two consecutive 14-day periods with either 30 mg bambuterol tablets once every evening or 2 x 5 mg terbutaline SR tablets morning and evening. The study had a double-blind, cross-over and randomized design. The mean evening peak expiratory flow rate (PEFR) (i.e. 24 h after intake of bambuterol and 12 h after intake of terbutaline SR) was significantly (p less than 0.001) higher during bambuterol than during terbutaline treatment (432 vs 415 l/min). The need for beta-adrenoceptor agonist aerosol in the daytime was significantly (p less than 0.05) lower during treatment with bambuterol once daily (0.70 puffs) than with terbutaline SR b.i.d. (1.04 puffs). The type and intensity of the side effects were the same during both treatments.
Induction of Vascular GTP-Cyclohydrolase I and Endogenous Tetrahydrobiopterin Synthesis Protect Against Inflammation-Induced Endothelial Dysfunction in Human Atherosclerosis
Authors: Charalambos Antoniades, Colin Cunnington, Alexis Antonopoulos, Matt Neville, Marios Margaritis, Michael Demosthenous, Jennifer Bendall, Ashley Hale, Ruha Cerrato, Dimitris Tousoulis, Constantinos Bakogiannis, Kyriakoula Marinou, Marina Toutouza, Charalambos Vlachopoulos, Paul Leeson, Christodoulos Stefanadis, Fredrik Karpe, Keith M. Channon
Journal: Circulation (2011)

The endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) is essential for maintenance of enzymatic function. We hypothesized that induction of BH4 synthesis might be an endothelial defense mechanism against inflammation in vascular disease states.In Study 1, 20 healthy individuals were randomized to receive Salmonella typhi vaccine (a model of acute inflammation) or placebo in a double-blind study. Vaccination increased circulating BH4 and interleukin 6 and induced endothelial dysfunction (as evaluated by brachial artery flow-mediated dilation) after 8 hours. In Study 2, a functional haplotype (X haplotype) in the GCH1 gene, encoding GTP-cyclohydrolase I, the rate-limiting enzyme in biopterin biosynthesis, was associated with endothelial dysfunction in the presence of high-sensitivity C-reactive protein in 440 coronary artery disease patients. In Study 3, 10 patients with coronary artery disease homozygotes for the GCH1 X haplotype (XX) and 40 without the haplotype (OO) underwent S Typhi vaccination. XX patients were unable to increase plasma BH4 and had a greater reduction of flow-mediated dilation than OO patients. In Study 4, vessel segments from 19 patients undergoing coronary bypass surgery were incubated with or without cytokines (interleukin-6/tumor necrosis factor-α/lipopolysaccharide) for 24 hours. Cytokine stimulation upregulated GCH1 expression, increased vascular BH4, and improved vasorelaxation in response to acetylcholine, which was inhibited by the GTP-cyclohydrolase inhibitor 2,4-diamino-6-hydroxypyrimidine.The ability to increase vascular GCH1 expression and BH4 synthesis in response to inflammation preserves endothelial function in inflammatory states. These novel findings identify BH4 as a vascular defense mechanism against inflammation-induced endothelial dysfunction.
Arkadia Regulates Tumor Metastasis by Modulation of the TGF-β Pathway
Authors: Marco A. Briones-Orta, Laurence Levy, Chris D. Madsen, Debipriya Das, Yigit Erker, Erik Sahai, Caroline S. Hill
Journal: Cancer Research (2013)

TGF-β can act as a tumor suppressor at early stages of cancer progression and as a tumor promoter at later stages. The E3 ubiquitin ligase Arkadia (RNF111) is a critical component of the TGF-β signaling pathway, being required for a subset of responses, those mediated by Smad3-Smad4 complexes. It acts by mediating ligand-induced degradation of Ski and SnoN (SKIL), which are 2 potent transcriptional repressors. Here, we investigate the role of Arkadia in cancer using model systems to address both potential tumor-suppressive and tumor-promoting roles. Stable reexpression of Arkadia in lung carcinoma NCI-H460 cells, which we show contain a hemizygous nonsense mutation in the Arkadia/RNF111 gene, efficiently restored TGF-β-induced Smad3-dependent transcription, and substantially decreased the ability of these cells to grow in soft agar in vitro. However, it had no effect on tumor growth in vivo in mouse models. Moreover, loss of Arkadia in cancer cell lines and human tumors is rare, arguing against a prominent tumor-suppressive role. In contrast, we have uncovered a potent tumor-promoting function for Arkadia. Using 3 different cancer cell lines whose tumorigenic properties are driven by TGF-β signaling, we show that loss of Arkadia function, either by overexpression of dominant negative Arkadia or by siRNA-induced knockdown, substantially inhibited lung colonization in tail vein injection experiments in immunodeficient mice. Our findings indicate that Arkadia is not critical for regulating tumor growth per se, but is required for the early stages of cancer cell colonization at the sites of metastasis.
Regulation of Replicative and Stress-Induced Senescence by RSK4, which is Down-regulated in Human Tumors
Authors: Laura López-Vicente, Gemma Armengol, Berta Pons, Laura Coch, Elisabet Argelaguet, Matilde Lleonart, Javier Hernández-Losa, Inés de Torres, Santiago Ramon y Cajal
Journal: Clinical Cancer Research (2009)

The control of senescence and its biochemical pathways is a crucial factor for understanding cell transformation. In a large RNA interference screen, the RSK4 gene was found to be related to p53-dependent arrest. The purpose of the present study was to investigate the potential role of RSK4 as a tumor suppressor gene.RSK4 expression was determined by quantitative real-time PCR and immunoblot in 30 colon and 20 renal carcinomas, and in 7 colon adenomas. Two HCT116 colon carcinoma cell lines (p53 wt and p53 null), IMR90 human fibroblasts, and E1A-expressing IMR90 cells were infected with RSK4 cDNA and/or shRNA. RSK4 expression levels were analyzed in HCT116 p53 wt or p53 null and IMR90 after senescence induction by quantitative real-time PCR and Western blot.The RSK4 gene was down-regulated in 27 of 30 colon carcinomas (P < 0.001), 16 of 20 renal cell carcinomas (P < 0.01), and 6 of 7 colon adenomas (P < 0.01). In vitro overexpression of RSK4 induced cell arrest and senescence features in normal fibroblasts and malignant colon carcinoma cell lines. Interestingly, in these cell lines RSK4 mRNA levels were increased both in replicative and stress-induced senescence. Moreover, IMR90 partially immortalized by RSK4 shRNA and HCT116 with this short hairpin RNA were more resistant to cisplatin treatment. Finally, cells expressing E1A or Rb short interfering RNA were resistant to RSK4-mediated senescence.These results support the concept that RSK4 may be an important tumor suppressor gene by modulating senescence induction and contributing to cell proliferation control in colon carcinogenesis and renal cell carcinomas.
Characterization of <i>CEBPA</i> Mutations in Acute Myeloid Leukemia: Most Patients with <i>CEBPA</i> Mutations Have Biallelic Mutations and Show a Distinct Immunophenotype of the Leukemic Cells
Authors: Liang-In Lin, Chien-Yuan Chen, Dong-Tsamn Lin, Woei Tsay, Jih-Luh Tang, You-Chia Yeh, Hwei-Ling Shen, Fang-Hsien Su, Ming Yao, Sheng-Yi Huang, Hwei-Fang Tien
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The transcription factor CCAAT/enhancer binding protein α, encoded by the CEBPA, is crucial for the differentiation of immature granulocytes. Mutation of the CEBPA may play an important role in leukemogenesis and prognosis. We sought to characterize the CEBPA mutation in acute myeloid leukemia (AML) and to clarify if there is a distinct immunophenotype for leukemic cells with the mutation. Experiment Design: One hundred and four patients with de novo AML were evaluated for the CEBPA mutation and immunophenotype of the leukemic cells. Results: Twenty-two distinct mutations were identified in 16 (15%) of 104 AML patients. Fourteen patients had biallelic mutations, mostly involving both the NH2-terminal TAD1 region and the COOH-terminal basic leucine zipper domain (bZIP). The mutations in the bZIP region were always tandem duplications and were located at hot-spot regions for topoisomerase II sites. Sequential study of the CEBPA mutations showed that the mutations disappeared at complete remission but the same mutations reappeared at relapse. None of the patients developed novel mutations during the follow-up period. Patients with CEBPA mutations had significantly higher incidences of CD7 (73%), CD15 (100%), CD34 (93%), and HLA-DR (93%) expression on the leukemic cells. Conclusion: These data revealed that most AML with CEBPA mutations were associated with an immunophenotype of HLA-DR+CD7+CD13+CD14−CD15+CD33+CD34+. The close relationship of CEBPA mutations with the leukemia status of the patients and the concordance of mutation in presenting and relapse samples implicate the CEBPA mutation as a potential marker for monitoring minimal residue disease.
Retinoic acid protects human breast cancer cells against etoposide-induced apoptosis by NF-kappaB-dependent but cIAP2-independent mechanisms
Authors: Ana M Jiménez-Lara, Ana Aranda, Hinrich Gronemeyer
Journal: Molecular Cancer (2010)

Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. These ligands can determine the ultimate fate of target cells by stimulating or repressing gene expression directly, or indirectly through crosstalking with other signal transducers. Using different breast cancer cell models, we show here that depending on the cellular context retinoids can signal either towards cell death or cell survival. Indeed, retinoids can induce the expression of pro-apoptotic (i.e. TRAIL, TNF-Related Apoptosis-Inducing Ligand, Apo2L/TNFSF10) and anti-apoptotic (i.e. cIAP2, inhibitor of apoptosis protein-2) genes. Promoter mapping, gel retardation and chromatin immunoprecipitation assays revealed that retinoids induce the expression of this gene mainly through crosstalk with NF-kappaB. Supporting this crosstalk, the activation of NF-kappaB by retinoids in T47D cells antagonizes the apoptosis triggered by the chemotherapeutic drugs etoposide, camptothecin or doxorubicin. Notably apoptosis induced by death ligands (i.e. TRAIL or antiFAS) is not antagonized by retinoids. That knockdown of cIAP2 expression by small interfering RNA does not alter the inhibition of etoposide-induced apoptosis by retinoids in T47D cells reveals that stimulation of cIAP2 expression is not the cause of their anti-apoptotic action. However, ectopic overexpression of a NF-kappaB repressor increases apoptosis by retinoids moderately and abrogates almost completely the retinoid-dependent inhibition of etoposide-induced apoptosis. Our data exclude cIAP2 and suggest that retinoids target other regulator(s) of the NF-kappaB signaling pathway to induce resistance to etoposide on certain breast cancer cells. This study shows an important role for the NF-kappaB pathway in retinoic acid signaling and retinoic acid-mediated resistance to cancer therapy-mediated apoptosis in breast cancer cells, independently of cIAP2. Our data support the use of NF-kappaB pathway activation as a marker for screening that will help to develop novel retinoids, or retinoid-based combination therapies with improved efficacy.
Tocopherols and the Etiology of Colon Cancer
Authors: W. L. Stone, A. M. Papas
Journal: JNCI Journal of the National Cancer Institute (1997)

Colorectal cancer is the second most common cause of cancer deaths in the United States for both sexes. Considerable evidence suggests that the risk of this cancer is increased by the mutagenic actions of free radicals, which are produced during oxidation reactions. Dietary factors, the intestinal flora (bacteria), and endogenously produced metabolites contribute to the production of free radicals in the colon. Dietary antioxidants, such as vitamin E, should reduce the levels of these harmful oxidation products. In the absence of vitamin E, polyunsaturated fats can be oxidized in the colon to produce mutagens, such as lipid hydroperoxides and malondialdehyde. Furthermore, fecal bacteria can generate a high flux of reactive oxygen species (e.g., the superoxide radical [O2*-]) at the surface of the intestinal lumen, and inflammatory cells in close proximity to the colon can produce reactive nitrogen species (e.g., nitrogen dioxide [NO2]). Increasing evidence suggests that the different chemical (e.g., alpha- and gamma-tocopherol) and stereochemical (e.g., RRR- and all-racemic-alpha-tocopherol) forms of vitamin E have distinct biologic potencies, pharmacokinetics, and different abilities to prevent neoplastic transformation. This review considers and evaluates recent studies relating vitamin E and oxidative stress to colon cancer, emphasizing the distinct roles of alpha- and gamma-tocopherols. In addition, recent findings on the antioxidant/pro-oxidant status of the digesta (ingested food) are discussed with respect to the use of antioxidants in chemo-prevention trials for colon cancer.
Energy, current, and success in defibrillation and cardioversion: clinical studies using an automated impedance-based method of energy adjustment.
Authors: R E Kerber, J B Martins, M G Kienzle, L Constantin, B Olshansky, R Hopson, F Charbonnier
Journal: Circulation (1988)

The purposes of this study were two. First, we wanted to evaluate in patients a technique for automated adjustment of selected energy for defibrillation or cardioversion based on transthoracic impedance. Second, we wanted to define the relationship of peak current and shock success in various arrhythmias. Applying a previously validated method of predicting transthoracic impedance in advance of any shock, we modified defibrillators to automatically double the operator-selected energy if the predicted impedance exceeded 70 omega. Success rates of shocks given for ventricular and atrial arrhythmias from these modified energy-adjusting defibrillators were compared with success rates for shocks given from standard defibrillators. We prospectively collected data on 347 patients who received a total of 1009 shocks. Low-energy (100 J) shocks given to high-impedance (greater than or equal to 70 omega) patients had a poor success rate; in such high-impedance patients significant improvement in shock success rate was achieved by the energy-adjusting defibrillators. For example, when 100 J shocks were selected for high-impedance patients in ventricular fibrillation the energy-adjusting defibrillators achieved a shock success rate of 75%, whereas standard defibrillators achieved a shock success rate of only 36% (p less than .01). Similar improvements were seen for ventricular tachycardia and atrial fibrillation. Thus, automated energy adjustment based on transthoracic impedance is a beneficial approach to defibrillation and cardioversion. For ventricular fibrillation, atrial fibrillation, and atrial flutter there was a clear relationship between peak current and shock success.(ABSTRACT TRUNCATED AT 250 WORDS)
Elevated Serum Uric Acid Concentrations Independently Predict Cardiovascular Mortality in Type 2 Diabetic Patients
Authors: Giacomo Zoppini, Giovanni Targher, Carlo Negri, Vincenzo Stoico, Fabrizia Perrone, Michele Muggeo, Enzo Bonora
Journal: Diabetes Care (2009)

OBJECTIVE There is limited information on whether increased serum uric acid levels are independently associated with cardiovascular mortality in type 2 diabetes. We assessed the predictive role of serum uric acid levels on all-cause and cardiovascular mortality in a large cohort of type 2 diabetic individuals. RESEARCH DESIGN AND METHODS The cohort included 2,726 type 2 diabetic outpatients, who were followed for a mean period of 4.7 years. The independent association of serum uric acid levels with all-cause and cardiovascular mortality was assessed by Cox proportional hazards models and adjusted for conventional risk factors and several potential confounders. RESULTS During follow-up, 329 (12.1%) patients died, 44.1% (n = 145) of whom from cardiovascular causes. In univariate analysis, higher serum uric acid levels were significantly associated with increased risk of all-cause (hazard ratio 19 [95% CI 1.12–1.27], P &amp;lt; 0.001) and cardiovascular (1.25 [1.16–1.34], P &amp;lt; 0.001) mortality. After adjustment for age, sex, BMI, smoking, hypertension, dyslipidemia, diabetes duration, A1C, medication use (allopurinol or hypoglycemic, antihypertensive, lipid-lowering, and antiplatelet drugs), estimated glomerular filtration rate, and albuminuria, the association of serum uric acid with cardiovascular mortality remained statistically significant (1.27 [1.01–1.61], P = 0.046), whereas the association of serum uric acid with all-cause mortality did not. CONCLUSIONS Higher serum uric acid levels are associated with increased risk of cardiovascular mortality in type 2 diabetic patients, independent of several potential confounders, including renal function measures.
A Young Adult Male with Chronic Mucocutaneous Candidiasis (CMC) with Signal Transduction and Activator of Transcription 1 (STAT 1) Mutation and Progressive Multifocal Leukoencephalopathy (PML)
Authors: Kathryn Marie Ruda Wessell, Steven Holland, Andrea Lisco, Chaim M. Roifman, Haig Tcheurekdjian, Robert W. Hostoffer
Journal: Journal of Allergy and Clinical Immunology (2015)
Financial cost of social exclusion: follow up study of antisocial children into
Authors: S. Scott, M. Knapp, J. Henderson, B. Maughan
Journal: BMJ (2001)

To compare the cumulative costs of public services used through to adulthood by individuals with three levels of antisocial behaviour in childhood.Costs applied to data of 10 year old children from the inner London longitudinal study selectively followed up to adulthood.Inner London borough.142 individuals divided into three groups in childhood: no problems, conduct problems, and conduct disorder.Costs in 1998 prices for public services (excluding private, voluntary agency, indirect, and personal costs) used over and above basic universal provision.By age 28, costs for individuals with conduct disorder were 10.0 times higher than for those with no problems (95% confidence interval of bootstrap ratio 3.6 to 20.9) and 3.5 times higher than for those with conduct problems (1.7 to 6.2). Mean individual total costs were 70 019 pounds sterling for the conduct disorder group (bootstrap mean difference from no problem group 62 pound sterling; 898 pound sterling 22 692 pound sterling to 117 pound sterling) and 24 324 pound sterling (16 707 pound sterling; 6594 pound sterling to 28 149 pound sterling) for the conduct problem group, compared with 7423 pound sterling for the no problem group. In all groups crime incurred the greatest cost, followed by extra educational provision, foster and residential care, and state benefits; health costs were smaller. Parental social class had a relatively small effect on antisocial behaviour, and although substantial independent contributions came from being male, having a low reading age, and attending more than two primary schools, conduct disorder still predicted the greatest cost.Antisocial behaviour in childhood is a major predictor of how much an individual will cost society. The cost is large and falls on many agencies, yet few agencies contribute to prevention, which could be cost effective.