tbuckley/cabot-search huggingface dataset:
An MRI Study of Basal Ganglia Volumes in First-Episode Schizophrenia Patients Treated With Risperidone
Authors: Donna J. Lang, Lili C. Kopala, Robert A. Vandorpe, Qing Rui, Geoffrey N. Smith, Vina M. Goghari, William G. Honer
Journal: American Journal of Psychiatry (2001)

OBJECTIVE: The basal ganglia may contribute to extrapyramidal movement disorders, affective disturbances, and cognitive deficits in schizophrenia. Basal ganglia volumes are putatively affected by antipsychotic medications. The purpose of this study was to determine the long-term effects of risperidone treatment in a cohort of first-episode patients with schizophrenia. METHOD: The subjects were 30 patients with first-episode schizophrenia, 12 patients chronically treated with typical antipsychotics, and 23 healthy comparison subjects. They were scanned by magnetic resonance imaging at baseline. The first-episode patients received 1 year of continuous risperidone treatment, after which they and the comparison subjects were rescanned. Caudate, putamen, and globus pallidus volumes were determined from coronal images. RESULTS: The baseline caudate, putamen, and globus pallidus volumes were significantly larger in the chronically treated patients than in the untreated first-episode subjects and comparison subjects. These volumes did not differ between the first-episode patients and healthy comparison subjects. Basal ganglia volumes were unchanged after 1 year of exposure to risperidone in the first-episode subjects. Extrapyramidal movement disorders were present in the majority of chronically treated patients and more than one-third of the never-medicated first-episode patients at baseline. CONCLUSIONS: This group of first-episode patients did not exhibit abnormalities of basal ganglia volumes, nor were basal ganglia volumes affected by exposure to risperidone. Movement disorders were observed in both first-episode and chronically treated patients, suggesting effects of both illness and medications.
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome
Authors: Maaike Luesink, Jeroen L. A. Pennings, Willemijn M. Wissink, Peter C. M. Linssen, Petra Muus, Rolph Pfundt, Theo J. M. de Witte, Bert A. van der Reijden, Joop H. Jansen
Journal: Blood (2009)
Dioxin receptor regulates aldehyde dehydrogenase to block melanoma tumorigenesis and metastasis
Authors: María Contador-Troca, Alberto Alvarez-Barrientos, Jaime M. Merino, Antonio Morales-Hernández, María I. Rodríguez, Javier Rey-Barroso, Eva Barrasa, María I. Cerezo-Guisado, Inmaculada Catalina-Fernández, Javier Sáenz-Santamaría, Francisco J. Oliver, Pedro M. Fernandez-Salguero
Journal: Molecular Cancer (2015)

The dioxin (AhR) receptor can have oncogenic or tumor suppressor activities depending on the phenotype of the target cell. We have shown that AhR knockdown promotes melanoma primary tumorigenesis and lung metastasis in the mouse and that human metastatic melanomas had reduced AhR levels with respect to benign nevi. Mouse melanoma B16F10 cells were engineered by retroviral transduction to stably downregulate AhR expression, Aldh1a1 expression or both. They were characterized for Aldh1a1 activity, stem cell markers and migration and invasion in vitro. Their tumorigenicity in vivo was analyzed using xenografts and lung metastasis assays as well as in vivo imaging. Depletion of aldehyde dehydrogenase 1a1 (Aldh1a1) impairs the pro-tumorigenic and pro-metastatic advantage of melanoma cells lacking AhR expression (sh-AhR). Thus, Aldh1a1 knockdown in sh-AhR cells (sh-AhR + sh-Aldh1a1) diminished their migration and invasion potentials and blocked tumor growth and metastasis to the lungs in immunocompetent AhR+/+ recipient mice. However, Aldh1a1 downmodulation in AhR-expressing B16F10 cells did not significantly affect tumor growth in vivo. Aldh1a1 knockdown reduced the high levels of CD133+/CD29+/CD44+ cells, melanosphere size and the expression of the pluripotency marker Sox2 in sh-AhR cells. Interestingly, Sox2 increased Aldh1a1 expression in sh-AhR but not in sh-AhR + sh-Aldh1a1 cells, suggesting that Aldh1a1 and Sox2 may be co-regulated in melanoma cells. In vivo imaging revealed that mice inoculated with AhR + Aldh1a1 knockdown cells had reduced tumor burden and enhanced survival than those receiving Aldh1a1-expressing sh-AhR cells. Aldh1a1 overactivation in an AhR-deficient background enhances melanoma progression. Since AhR may antagonize the protumoral effects of Aldh1a1, the AhRlow-Aldh1a1high phenotype could be indicative of bad outcome in melanoma.
Risk Factors Of High Feno Levels &amp; Cut-Off Value Of Feno In Elementary School Children With Asthma
Authors: Hyun Ju Cho, Young-Ho Ho Jung, Eun Lee, Song I. Yang, Hyung Young Kim, Ju-Hee Seo, Ji-Won Kwon, Byoung-Ju Kim, Hyo-Bin Kim, So Yeon Lee, Dae Jin Song, Woo-Kyung Kim, Gwang Cheon Jang, Jung Yeon Shim, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2014)
National Burden of Invasive Methicillin-Resistant<i>Staphylococcus aureus</i>Infections, United States, 2011
Authors: Raymund Dantes, Yi Mu, Ruth Belflower, Deborah Aragon, Ghinwa Dumyati, Lee H. Harrison, Fernanda C. Lessa, Ruth Lynfield, Joelle Nadle, Susan Petit, Susan M. Ray, William Schaffner, John Townes, Scott Fridkin
Journal: JAMA Internal Medicine (2013)

Estimating the US burden of methicillin-resistant Staphylococcus aureus (MRSA) infections is important for planning and tracking success of prevention strategies.
Monoclonal antibody against an Ir gene product?
Authors: E A Lerner, L A Matis, C A Janeway, P P Jones, R H Schwartz, D B Murphy
Journal: The Journal of Experimental Medicine (1980)

Genetic, biochemical, and functional studies have been performed using a monoclonal antibody, Y-17, directed at a conformational or combinatorial determinant formed by certain Ae:E alpha complexes. This determinant appears to be a marker present on a subset of B cells as well as on non-T and non-B spleen cells. Besides Ae and E alpha chains, Y-17 precipitates a third chain that is indistinguishable from the A alpha chain in two-dimensional gels. This results suggests additional combinatorial complexity in the generation of I-region encoded antigens. Y-17 can inhibit the response of T cells to Ae:E alpha determinants in mixed lymphocyte cultures. Furthermore, Y-17 blocks antigen-specific T cell proliferative responses to GLPhe and pigeon cytochrome c which have been shown to require the Ae:E alpha complex as a restriction element for antigen presentation. These results provide strong evidence for the molecular identity of Ia antigens, Ir-gene products and Lad antigens.
Effects of Coffee Consumption on Fasting Blood Glucose and Insulin Concentrations
Authors: Rob M. van Dam, Wilrike J. Pasman, Petra Verhoef
Journal: Diabetes Care (2004)

Higher habitual coffee consumption was associated with higher insulin sensitivity (1) and a lower risk for type 2 diabetes (2–6) in diverse populations. In contrast, short-term metabolic studies showed that caffeine intake can acutely lower insulin sensitivity (7–9) and increase glucose concentrations (10–15). Randomized intervention studies are needed to examine whether tolerance to these acute effects develops after longer-term consumption (16). We therefore examined the effects of coffee and caffeine on fasting blood concentrations of glucose and insulin over 2–4 weeks in two crossover studies in healthy volunteers.

The studies were approved by the TNO Nutrition and Food Research Medical Ethics Committee, and all participants gave informed consent. The trials were originally designed to study the effects of coffee and caffeine on plasma concentrations of homocysteine, and the study designs have been reported in detail previously (17,18). Participants were regular coffee consumers (more than five cups/day) and did not have known diabetes.

The first study was a 4-week crossover study that compared the effects of regular paper-filtered coffee consumption with that of coffee abstinence. A total of 40 volunteers used 1 l of coffee (70 g coffee grounds) for 4 weeks and abstained from coffee for 4 weeks in random order. Fourteen participants did not complete the trial because of nausea and restlessness ( n = …
Is there a relationship between Mycobacterium tuberculosis strain type and TB paradoxical reaction?
Authors: F M R Perrin
Journal: Thorax (2005)

Comorbidity in elderly NSCLC patientsWe read with interest the report by Janssen-Heijnen and associates on the effect of comorbidity on the treatment and prognosis of elderly patients with non-small cell lung cancer (NSCLC). 1 The authors concluded that the number of comorbid conditions had no significant influence on the treatment chosen for patients with non-localised disease.We share the authors' opinion that ''comorbidity had no independent prognostic effect''.In their report, the authors used the Charlson comorbidity index and analysed the number of comorbid conditions. 1 However, they did not examine the scoring system of the index.We would like to know why the authors did not use the scoring of the index, and whether the conclusion would be changed if the scoring system was used.In the original article by Charlson et al and other related studies, 2-5 ''angina pectoris'' was not evaluated as one of the cardiovascular comorbid diseases.However, Janssen-Heijnen et al 1 included ''angina pectoris'' as a comorbid disease although they did not describe it precisely.We consider this inclusion is reasonable, and we would appreciate hearing from the authors whether ''angina pectoris'' would be evaluated as one of the cardiovascular comorbid diseases in future studies to evaluate the effect on mortality, and what score it should be assigned.
Infertility, infertility treatment, and achievement of pregnancy in female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study cohort
Authors: Sara E Barton, Julie S Najita, Elizabeth S Ginsburg, Wendy M Leisenring, Marilyn Stovall, Rita E Weathers, Charles A Sklar, Leslie L Robison, Lisa Diller
Journal: The Lancet Oncology (2013)
Detection of helicobacter pylori by PCR in idiopathic pulmonary fibrosis (IPF) lung biopsies
Authors: Michael Kreuter, Detlef Kirsten, Roland Penzel, Ute Oltmanns, Svenja Ehlers-Tenenbaum, Karin Palmowski, Annette Traeger, Philipp A. Schnabel, Claus Peter Heussel, Felix J.F. Herth, Arne Warth
Journal: European Respiratory Journal (2014)

Objective: Increasing evidence suggests a role of gastroesophageal reflux (GER) in IPF pathogenesis. Recently, an association of serum Helicobacter pylori (HP) antibody positivity with more severe disease was described. Here, we report screening for HP in IPF lung tissue by PCR.  Patients and methods: Our IPF data base (n=354) was screened for available lung biopsy material at IPF first diagnosis. Clinical and radiological data, especially the presence of GER and antacid medication were evaluated. Extraction of genomic DNA was performed by proteinase K digestion and fully automated purification using a QIASymphony SP (Qiagen, Hilden, Germany). HP specific PCR was carried out with the following primers: HP 16S rRNA (forward) 59- CTG GAG AGA CTA AGC CCT CC-39 and HP 16S rRNA (reverse) 59- ATT ACT GAC GCT GAT TGT GC-39. HP+ gastric biopsies served as positive controls.  Results: 26 IPF patients (85% male, medians: age 70 years, FVC 77%pred, DLCO 60%pred, 73% surgical / 27% transbronchial lung biopsies) were identified. Comorbidities: GER 27% (n=7), diabetes mellitus 27%, sleep apnea 8%, hiatal hernia (HRCT) 4%. PPI were prescribed at time of biopsy in 15% (n=4). After a median follow up of 28 (range 6-69) months, 1 death, 1 lung transplantation and 23% acute exacerbations were recorded without relevant differences in the GER and non-GER subgroups. HP DNA was not detected in any of the IPF tissue samples.  Conclusion: The negative findings of our study question the proposed relevance of HP in the pathogenesis of IPF, however, since only patients with mild-moderate IPF were included, a role of HP in more advanced IPF cannot be ruled out and needs further consideration.
Community-wide analysis of microbial genome sequence signatures
Authors: Gregory J Dick, Anders F Andersson, Brett J Baker, Sheri L Simmons, Brian C Thomas, A Pepper Yelton, Jillian F Banfield
Journal: Genome biology (2009)

Abstract Background Analyses of DNA sequences from cultivated microorganisms have revealed genome-wide, taxa-specific nucleotide compositional characteristics, referred to as genome signatures. These signatures have far-reaching implications for understanding genome evolution and potential application in classification of metagenomic sequence fragments. However, little is known regarding the distribution of genome signatures in natural microbial communities or the extent to which environmental factors shape them. Results We analyzed metagenomic sequence data from two acidophilic biofilm communities, including composite genomes reconstructed for nine archaea, three bacteria, and numerous associated viruses, as well as thousands of unassigned fragments from strain variants and low-abundance organisms. Genome signatures, in the form of tetranucleotide frequencies analyzed by emergent self-organizing maps, segregated sequences from all known populations sharing &lt; 50 to 60% average amino acid identity and revealed previously unknown genomic clusters corresponding to low-abundance organisms and a putative plasmid. Signatures were pervasive genome-wide. Clusters were resolved because intra-genome differences resulting from translational selection or protein adaptation to the intracellular (pH ~5) versus extracellular (pH ~1) environment were small relative to inter-genome differences. We found that these genome signatures stem from multiple influences but are primarily manifested through codon composition, which we propose is the result of genome-specific mutational biases. Conclusions An important conclusion is that shared environmental pressures and interactions among coevolving organisms do not obscure genome signatures in acid mine drainage communities. Thus, genome signatures can be used to assign sequence fragments to populations, an essential prerequisite if metagenomics is to provide ecological and biochemical insights into the functioning of microbial communities.
Somatic Mutations of Epidermal Growth Factor Receptor in Bile Duct and Gallbladder Carcinoma
Authors: Francesco Leone, Giuliana Cavalloni, Ymera Pignochino, Ivana Sarotto, Renato Ferraris, Wanda Piacibello, Tiziana Venesio, Lorenzo Capussotti, Mauro Risio, Massimo Aglietta
Journal: Clinical Cancer Research (2006)

Abstract Objective: Conventional therapies are still unsuccessful in patients with carcinoma arising from the biliary tract. Somatic mutations of the epidermal growth factor receptor (EGFR) gene and the activation of its downstream pathways predict the sensitivity to small-molecule inhibitors in non–small cell lung carcinoma. Therefore, we analyzed EGFR mutations and related pathways in gallbladder and bile duct carcinomas to consider the possible application of these alternative therapeutic strategies. Experimental Design: Forty paraffin-embedded samples, including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder carcinoma, were studied after tumor cell isolation by laser microdissection and sequencing of EGFR tyrosine kinase domain (exons 18-21). Activation of EGFR pathway was studied by evaluating phosphorylation of mitogen-activated protein kinase and Akt. Results: None of the 40 specimens had mutations in exon 18; one had one missense point mutation in exon 19, two in exon 20, and three in exon 21. In addition, 36 of 40 specimens had the same silent mutation at codon 787 in exon 20, which was also found in peripheral blood cells from healthy donors. Tumor samples harboring EGFR mutation had phosphorylation of one or both downstream transducers analyzed. Conclusions: This is the first evidence of somatic mutations of the EGFR gene in bile duct carcinoma. Our findings suggest that a subgroup of patients with cholangiocarcinoma or gallbladder carcinoma exhibits somatic mutations of EGFR in the tyrosine kinase domain that can elicit cell signals sustaining survival and proliferation. These tumors might be further evaluated for their susceptibility to small-molecule inhibitor treatment.
Effect of low-dose acetazolamide on the ventilatory CO2 response during hypoxia in the anaesthetized cat
Authors: M Wagenaar, L Teppema, A Berkenbosch, C Olievier, H Folgering
Journal: European Respiratory Journal (1998)

Acetazolamide, a carbonic anhydrase inhibitor, is used in patients with chronic obstructive pulmonary diseases and central sleep apnoea syndrome and in the prevention and treatment of the symptoms of acute mountain sickness. In these patients, the drug increases minute ventilation (V'E), resulting in an improvement in arterial oxygen saturation. However, the mechanism by which it stimulates ventilation is still under debate. Since hypoxaemia is a frequently observed phenomenon in these patients, the effect of 4 mg x kg(-1) acetazolamide (i.v.) on the ventilatory response to hypercapnia during hypoxaemia (arterial oxygen tension (Pa,O2)=6.8+/-0.8 kPa, mean+/-SD) was investigated in seven anaesthetized cats. The dynamic end-tidal forcing (DEF) technique was used, enabling the relative contributions of the peripheral and central chemoreflex loops to the ventilatory response to a step change in end-tidal carbon dioxide tension, (PET,CO2) to be separated. Acetazolamide reduced the CO2 sensitivities of the peripheral (Sp) and central (Sc) chemoreflex loops from 0.22+/-0.08 to 0.11+/-0.03 L x min(-1) x kPa(-1) (mean+/-SD) (p&lt;0.01) and from 0.74+/-0.32 to 0.40+/-0.10 L x min(-1) x kPa(-1) (p&lt;0.01), respectively. The apnoeic threshold B (x-intercept of the ventilatory CO2 response curve) decreased from 2.88+/-0.97 to 0.95+/-0.92 kPa (p&lt;0.01). The net result was a stimulation of ventilation at PET,CO2 &lt;5 kPa. The effect of acetazolamide is possibly due to a direct effect on the peripheral chemoreceptors as well as to an effect on the cerebral blood flow regulation. Possible clinical implications of these results are discussed.
Cardiac-Specific Loss of N-Cadherin Leads to Alteration in Connexins With Conduction Slowing and Arrhythmogenesis
Authors: Jifen Li, Vickas V. Patel, Igor Kostetskii, Yanming Xiong, Antony F. Chu, Jason T. Jacobson, Cindy Yu, Gregory E. Morley, Jeffery D. Molkentin, Glenn L. Radice
Journal: Circulation Research (2005)

The remodeling of ventricular gap junctions, as defined by changes in size, distribution, or function, is a prominent feature of diseased myocardium. However, the regulation of assembly and maintenance of gap junctions remains poorly understood. To investigate N-cadherin function in the adult myocardium, we used a floxed N-cadherin gene in conjunction with a cardiac-specific tamoxifen-inducible Cre transgene. The mutant animals appeared active and healthy until their sudden death approximately 2 months after deleting N-cadherin from the heart. Electrophysiologic analysis revealed abnormal conduction in the ventricles of mutant animals, including diminished QRS complex amplitude consistent with loss of electrical coupling in the myocardium. A significant decrease in the gap junction proteins, connexin-43 and connexin-40, was observed in N-cadherin-depleted myocytes. Perturbation of connexin function resulted in decreased ventricular conduction velocity, as determined by optical mapping. Our data suggest that perturbation of the N-cadherin/catenin complex in heart disease may be an underlying cause, leading to the establishment of the arrythmogenic substrate by destabilizing gap junctions at the cell surface.
Discovery and Evaluation of Dual CDK1 and CDK2 Inhibitors
Authors: Marc Payton, Grace Chung, Peter Yakowec, Andrew Wong, Dave Powers, Ling Xiong, Nancy Zhang, Juan Leal, Tammy L. Bush, Vincent Santora, Ben Askew, Andrew Tasker, Robert Radinsky, Richard Kendall, Steve Coats
Journal: Cancer Research (2006)

In eukaryotic cells, cyclin-dependent kinase (CDK) complexes regulate the temporal progression of cells through the cell cycle. Deregulation in the cell cycle is an essential component in the evolution of cancer. Here, we validate CDK1 and CDK2 as potential therapeutic targets using novel selective small-molecule inhibitors of cyclin B1/CDK1 and cyclin E2/CDK2 enzyme complexes (CDKi). Flow cytometry-based methods were developed to assess intracellular retinoblastoma (Rb) phosphorylation to show inhibition of the CDK pathway. Tumor cells treated with CDK inhibitors showed an overall decrease in cell proliferation, accumulation of cells in G1 and G2, and apoptosis in a cell line-specific manner. Although CDK inhibitors activate p53, the inhibitors were equipotent in arresting the cell cycle in isogenic breast and colon tumor cells lacking p53, suggesting the response is independent of p53. In vivo, the CDK inhibitors prevented the growth of colon and prostate tumors, blocked proliferation of tumor cells, and inhibited Rb phosphorylation. The discovery and evaluation of novel potent and selective CDK1 and CDK2 inhibitors will help delineate the role that CDK complexes play in regulating tumorigenesis.
Oxido-reductive regulation of vascular remodeling by receptor tyrosine kinase ROS1
Authors: Ziad A. Ali, Vinicio de Jesus Perez, Ke Yuan, Mark Orcholski, Stephen Pan, Wei Qi, Gaurav Chopra, Christopher Adams, Yoko Kojima, Nicholas J. Leeper, Xiumei Qu, Kathia Zaleta-Rivera, Kimihiko Kato, Yoshiji Yamada, Mitsutoshi Oguri, Allan Kuchinsky, Stanley L. Hazen, J. Wouter Jukema, Santhi K. Ganesh, Elizabeth G. Nabel, Keith Channon, Martin B. Leon, Alain Charest, Thomas Quertermous, Euan A. Ashley
Journal: Journal of Clinical Investigation (2014)

Angioplasty and stenting is the primary treatment for flow-limiting atherosclerosis; however, this strategy is limited by pathological vascular remodeling. Using a systems approach, we identified a role for the network hub gene glutathione peroxidase-1 (GPX1) in pathological remodeling following human blood vessel stenting. Constitutive deletion of Gpx1 in atherosclerotic mice recapitulated this phenotype of increased vascular smooth muscle cell (VSMC) proliferation and plaque formation. In an independent patient cohort, gene variant pair analysis identified an interaction of GPX1 with the orphan protooncogene receptor tyrosine kinase ROS1. A meta-analysis of the only genome-wide association studies of human neointima-induced in-stent stenosis confirmed the association of the ROS1 variant with pathological remodeling. Decreased GPX1 expression in atherosclerotic mice led to reductive stress via a time-dependent increase in glutathione, corresponding to phosphorylation of the ROS1 kinase activation site Y2274. Loss of GPX1 function was associated with both oxidative and reductive stress, the latter driving ROS1 activity via s-glutathiolation of critical residues of the ROS1 tyrosine phosphatase SHP-2. ROS1 inhibition with crizotinib and deglutathiolation of SHP-2 abolished GPX1-mediated increases in VSMC proliferation while leaving endothelialization intact. Our results indicate that GPX1-dependent alterations in oxido-reductive stress promote ROS1 activation and mediate vascular remodeling.
Metabolism and Function of <i>myo</i>-Inositol and Inositol Phospholipids
Authors: Bruce J. Holub
Journal: Annual Review of Nutrition (1986)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More