tbuckley/cabot-search huggingface dataset:
Functional Imaging of Endocrine Tumors: Role of Positron Emission Tomography
Authors: Karel Pacak, Graeme Eisenhofer, David S. Goldstein
Journal: Endocrine Reviews (2004)

This article provides an update on functional imaging approaches for diagnostic localization of endocrine tumors, with emphasis on positron emission tomography (PET). [18F]Fluorodeoxyglucose PET scanning is now a widely accepted imaging approach in clinical oncology. Benefits include improved patient outcome facilitated by staging and monitoring of disease and better treatment planning. [18F]Fluorodeoxyglucose PET is also useful in some endocrine tumors, particularly in recurrent or metastatic thyroid cancer where the degree of accumulation of the radionuclide has prognostic value. However, this imaging approach does not take full advantage of the unique characteristics of endocrine tumors. Endocrine tumor cells take up hormone precursors, express receptors and transporters, and synthesize, store, and release hormones. These characteristics offer highly specific targets for PET. Radiopharmaceuticals developed for such approaches include 6-[18F]fluorodopamine, and [11C]hydroxyephedrine for localization of pheochromocytomas, [11C]5-hydroxytryptophan and [11C]l-dihydroxyphenylalanine for carcinoid tumors, and [11C]metomidate for adrenocortical tumors. These functional imaging approaches are not meant to supplant conventional imaging modalities but should be used conjointly to better identify specific characteristics of endocrine tumors. This represents a relatively new and evolving approach to imaging that promises to answer specific questions about the behavior and growth of endocrine tumors, their malignant potential, and responsiveness to different treatment modalities.
Tracheobronchial stenosis in Keutel syndrome
Authors: M. Meier, L.P. Weng, E. Alexandrakis, J. Rüschoff, G. Goeckenjan
Journal: European Respiratory Journal (2001)

In 1971 Keutel et al . described a new syndrome in two siblings presenting with peripheral pulmonary stenoses, brachytelephalangism, neural hearing loss and abnormal cartilage calcification. Recent investigations provided evidence that mutations in the gene encoding the human matrix GLA protein cause Keutel syndrome. With these new insights in the disease the symptomatology of Keutel syndrome was reassessed. The follow-up of the two siblings was studied by clinical and post mortem examination. As a new feature of Keutel syndrome tracheobronchial stenosis and concentric calcification of pulmonary, coronary, hepatic, renal, meningeal and cerebral arteries were described. Complementary to the results in molecular genetics the symptomatology of Keutel syndrome could be revised by clinical and post mortem examination.
Direct recognition and lysis of leukemia cells by WT1-specific CD4+ T lymphocytes in an HLA class II-restricted manner
Authors: Yun Guo, Hironari Niiya, Taichi Azuma, Naoyuki Uchida, Yoshihiro Yakushijin, Ikuya Sakai, Takaaki Hato, Masuhiro Takahashi, Satoru Senju, Yasuharu Nishimura, Masaki Yasukawa
Journal: Blood (2005)
Genome-wide distribution of 5-formylcytosine in embryonic stem cells is associated with transcription and depends on thymine DNA glycosylase
Authors: Eun-Ang Raiber, Dario Beraldi, Gabriella Ficz, Heather E Burgess, Miguel R Branco, Pierre Murat, David Oxley, Michael J Booth, Wolf Reik, Shankar Balasubramanian
Journal: Genome biology (2012)

Methylation of cytosine in DNA (5mC) is an important epigenetic mark that is involved in the regulation of genome function. During early embryonic development in mammals, the methylation landscape is dynamically reprogrammed in part through active demethylation. Recent advances have identified key players involved in active demethylation pathways, including oxidation of 5mC to 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC) by the TET enzymes, and excision of 5fC by the base excision repair enzyme thymine DNA glycosylase (TDG). Here, we provide the first genome-wide map of 5fC in mouse embryonic stem (ES) cells and evaluate potential roles for 5fC in differentiation. Our method exploits the unique reactivity of 5fC for pulldown and high-throughput sequencing. Genome-wide mapping revealed 5fC enrichment in CpG islands (CGIs) of promoters and exons. CGI promoters in which 5fC was relatively more enriched than 5mC or 5hmC corresponded to transcriptionally active genes. Accordingly, 5fC-rich promoters had elevated H3K4me3 levels, associated with active transcription, and were frequently bound by RNA polymerase II. TDG down-regulation led to 5fC accumulation in CGIs in ES cells, which correlates with increased methylation in these genomic regions during differentiation of ES cells in wild-type and TDG knockout contexts. Collectively, our data suggest that 5fC plays a role in epigenetic reprogramming within specific genomic regions, which is controlled in part by TDG-mediated excision. Notably, 5fC excision in ES cells is necessary for the correct establishment of CGI methylation patterns during differentiation and hence for appropriate patterns of gene expression during development.
Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation
Authors: Prerana Jha, Irene Rosita Pia Patric, Sudhanshu Shukla, Pankaj Pathak, Jagriti Pal, Vikas Sharma, Sivaarumugam Thinagararanjan, Vani Santosh, Vaishali Suri, Mehar Chand Sharma, Arimappamagan Arivazhagan, Ashish Suri, Deepak Gupta, Kumaravel Somasundaram, Chitra Sarkar
Journal: Neuro-Oncology (2014)

Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine–phosphate–guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine–phosphate–guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation–specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation.
A novel, NH2-terminal sequence-characterized human monokine possessing neutrophil chemotactic, skin-reactive, and granulocytosis-promoting activity.
Authors: J Van Damme, J Van Beeumen, G Opdenakker, A Billiau
Journal: The Journal of Experimental Medicine (1988)

A factor able to induce an early local inflammation in rabbit skin was detected in the supernatant of mitogen-stimulated human blood leukocytes. The factor was different from IL-1 which, although present in the supernatants, was chemically separable from the factor and induced a late rather than an early skin response. Other biological effects of the principal factor were its in vitro chemotactic effects on granulocytes and its ability to induce rapid granulocytosis upon intravenous injection in rabbits. When tested under the same conditions, IL-1 beta did not act chemotactically and induced granulocytosis at a later time. The factor was purified to homogeneity and identified by electrophoretic mobility as a protein of Mr 6,500. Amino acid sequence analysis revealed the presence of an uncontaminated NH2-terminal sequence identical to a segment of the sequence previously predicted from the cDNA clone (3-10C) copied from an mRNA isolated from human leukocytes and coding for a protein of unknown function. The NH2-terminal sequence of the factor also showed extensive homology to that of the platelet factors beta-thromboglobulin (beta TG) and platelet factor 4 (PF-4). Studies done to identify the cell source of the factor revealed that it was produced by adherent mononuclear cells but not by platelets, while the opposite was true for beta TG.
Effect of DHA Supplementation During Pregnancy on Maternal Depression and Neurodevelopment of Young Children
Authors: Maria Makrides, Robert A. Gibson, Andrew J. McPhee, Lisa Yelland, Julie Quinlivan, Philip Ryan, and the DOMInO Investigative Team
Journal: JAMA (2010)

Uncertainty about the benefits of dietary docosahexaenoic acid (DHA) for pregnant women and their children exists, despite international recommendations that pregnant women increase their DHA intakes.To determine whether increasing DHA during the last half of pregnancy will result in fewer women with high levels of depressive symptoms and enhance the neurodevelopmental outcome of their children.A double-blind, multicenter, randomized controlled trial (DHA to Optimize Mother Infant Outcome [DOMInO] trial) in 5 Australian maternity hospitals of 2399 women who were less than 21 weeks' gestation with singleton pregnancies and who were recruited between October 31, 2005, and January 11, 2008. Follow-up of children (n = 726) was completed December 16, 2009.Docosahexaenoic acid-rich fish oil capsules (providing 800 mg/d of DHA) or matched vegetable oil capsules without DHA from study entry to birth.High levels of depressive symptoms in mothers as indicated by a score of more than 12 on the Edinburgh Postnatal Depression Scale at 6 weeks or 6 months postpartum. Cognitive and language development in children as assessed by the Bayley Scales of Infant and Toddler Development, Third Edition, at 18 months.Of 2399 women enrolled, 96.7% completed the trial. The percentage of women with high levels of depressive symptoms during the first 6 months postpartum did not differ between the DHA and control groups (9.67% vs 11.19%; adjusted relative risk, 0.85; 95% confidence interval [CI], 0.70-1.02; P = .09). Mean cognitive composite scores (adjusted mean difference, 0.01; 95% CI, -1.36 to 1.37; P = .99) and mean language composite scores (adjusted mean difference, -1.42; 95% CI, -3.07 to 0.22; P = .09) of children in the DHA group did not differ from children in the control group.The use of DHA-rich fish oil capsules compared with vegetable oil capsules during pregnancy did not result in lower levels of postpartum depression in mothers or improved cognitive and language development in their offspring during early childhood.anzctr.org.au Identifier: ACTRN12605000569606.
Recent Advances in the Development of HIV-1 Vaccines Using Replication-Incompetent Adenovirus Vectors
Authors: John W. Shiver, Emilio A. Emini
Journal: Annual Review of Medicine (2004)

An increasing body of evidence suggests that a vaccine that elicits anti-HIV-1 cellular immunity could provide the basis for an effective AIDS vaccine. Comparative immunization experiments testing a variety of vaccine approaches have demonstrated that replication-incompetent adenovirus vectors are an effective means for eliciting cytotoxic T-lymphocyte (CTL) immune responses against HIV-1 antigens. These immune responses effectively control viremia in nonhuman primates following challenge with simian AIDS viruses. Such data, coupled with epidemiology studies that identify HIV-1 gag, pol, and nef as the best antigens for broadly directed cellular immune responses, provide guidance for the development of a potential AIDS vaccine.
Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD
Authors: Matthew Maddocks, Dinesh Shrikrishna, Simone Vitoriano, Samantha A. Natanek, Rebecca J. Tanner, Nicholas Hart, Paul R. Kemp, John Moxham, Michael I. Polkey, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2014)

Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy. We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population. In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190– -30 HU; skeletal muscle -29–150 HU. Mean± sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03). Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength. Combined with transfer factor of the lung for carbon monoxide, these variables could identify &gt;80% of patients with fibre type shift with &gt;65% specificity (area under the curve 0.83, 95% CI 0.72–0.95). Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes.
Efficient retrovirus-mediated PIG-A gene transfer and stable restoration of GPI-anchored protein expression in cells with the PNH phenotype
Authors: Jun-ichi Nishimura, Ken L. Phillips, Russell E. Ware, Sharon Hall, Lee Wilson, Tracy L. Gentry, Thad A. Howard, Yoshiko Murakami, Masaru Shibano, Takashi Machii, Eli Gilboa, Yuzuru Kanakura, Junji Takeda, Taroh Kinoshita, Wendell F. Rosse, Clay A. Smith
Journal: Blood (2001)
Oxidative stress and left ventricular remodelling after myocardial infarction
Authors: M. Hori, K. Nishida
Journal: Cardiovascular Research (2008)

In acute myocardial infarction (MI), reactive oxygen species (ROS) are generated in the ischaemic myocardium especially after reperfusion. ROS directly injure the cell membrane and cause cell death. However, ROS also stimulate signal transduction to elaborate inflammatory cytokines, e.g. tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and -6, in the ischaemic region and surrounding myocardium as a host reaction. Inflammatory cytokines also regulate cell survival and cell death in the chain reaction with ROS. Both ROS and inflammatory cytokines are cardiodepressant mainly due to impairment of intracellular Ca2+ homeostasis. Inflammatory cytokines stimulate apoptosis through a TNF-α receptor/caspase pathway, whereas Ca2+ overload induced by extensive ROS generation causes necrosis through enhanced permeability of the mitochondrial membrane (mitochondrial permeability transition). Apoptosis signal-regulating kinase-1 (ASK1) is an ROS-sensitive, mitogen-activated protein kinase kinase kinase that is activated by many stress signals and can activate nuclear factor κB and other transcription factors. ASK1-deficient mice demonstrate that the ROS/ASK1 pathway is involved in necrotic as well as apoptotic cell death, indicating that ASK1 may be a therapeutic target to reduce left ventricular (LV) remodelling after MI. ROS and inflammatory cytokines activate matrix metalloproteinases which degrade extracellular matrix, causing a slippage of myofibrils and hence LV dilatation. Consequently, collagen deposition is increased and tissue repair is enhanced with myocardial fibrosis and angiogenesis. Since the extent of LV remodelling is a major predictor of prognosis of the patients with MI, the therapeutic approach to attenuating LV remodelling is critically important.
Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial
Authors: J.-Y. Pierga, F.-C. Bidard, C. Cropet, P. Tresca, F. Dalenc, G. Romieu, M. Campone, C. Mahier Aït-Oukhatar, E. Le Rhun, A. Gonçalves, M. Leheurteur, J. Dômont, M. Gutierrez, H. Curé, J.-M. Ferrero, C. Labbe-Devilliers, T. Bachelot
Journal: Annals of Oncology (2013)
Complications at site of injection of depot neuroleptics
Authors: J. Hay
Journal: BMJ (1995)

Although depot preparations are used extensively in psychiatry, few published reports mention the occurrence of complications at the site of injection. There are occasional reports of subcutaneous lumps and indurations; muscle granulomas; medication oozing from, and fibrosis at, the injection site; abscess formation; and the accumulation of oil after repeated large volume injections.1 Such local complications can affect quality of life and adversely influence compliance. They are potentially dangerous and may alter the bioavailability. If severe they can prevent further injections.

The results of a number of recent studies suggest that the incidence of these local complications has been underestimated.2 I therefore undertook this prospective study to estimate the prevalence and type of injection complications and, if possible, to determine which variables were associated with local reactions.

Complications were divided into acute and chronic types. Acute problems occurred as discrete …
Vascular endothelial growth factor in pleural effusions of different origin
Authors: U. Sack, M. Hoffmann, X. J. Zhao, K. S. Chan, D. S. C. Hui, H. Gosse, L. Engelmann, J. Schauer, F. Emmrich, G. Hoheisel
Journal: European Respiratory Journal (2005)

This study aimed to determine the diagnostic relevance of vascular endothelial growth factor (VEGF) in the pleural fluid and serum of patients with pleural effusions of different aetiology. VEGF was quantified in the pleural effusion fluid and serum of 96 patients with malignancies (58 lung cancers (CA) and 38 tumours with secondaries to the lung (TM)), 45 with congestive heart failure (CHF), 28 with tuberculosis (TB), 45 with acute infections (INF), and in the serum of 20 healthy controls. VEGF pleural effusion concentrations were significantly different in the main diagnostic groups. VEGF was higher in effusions of patients with malignancies (CA as well as TM) in comparison with INF, TB or CHF. In serum, however, high VEGF concentrations indicated CA, TM or INF, but not TB or CHF. Despite significant differences of VEGF levels in different patient groups, receiver-operating characteristic analysis revealed insufficient diagnostic value of VEGF for differential diagnosis of pleural effusions. In conclusion, vascular endothelial growth factor serum concentration is highly suggestive of the presence of lung disease in general, except for tuberculosis. In effusion fluid, the presence of vascular endothelial growth factor clearly indicates inflammatory or malignant origin. However, for diagnostic use, additional parameters besides vascular endothelial growth factor are mandatory.
Feedback Inhibition of Purine Biosynthesis in Adenocarcinoma 755 and Sarcoma 180 Cells in Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G J Dixon, E A Dulmadge, R W Brockman, S C Shaddix
Journal: JNCI Journal of the National Cancer Institute (1970)

In vivo, Adenocarcinoma 755 (Ca 755) is much more sensitive to purine antagonists than is Sarcoma 180 (Sa 180). This difference in sensitivity apparently is unrelated to the capability of these two tumors to form ribonucleotides from purine bases, since both tumors possess essentially equal degrees of these enzymatic capacities. Experiments were performed with adenine, hypoxanthine, 6-mercaptopurine, and 6-thioguanine as possible feedback or pseudofeedback inhibitors of purine biosynthesis after their conversion to ribonucleotides in the intact cells. Purine synthesis de novo was blocked by azaserine, and the effectiveness of the candidate feedback inhibitors was measured by the decrease in 14C-labeled formylglycinamide ribonucleotide accumulating as a result of the azaserine block. Adenine and hypoxanthine at low concentrations were much more effective inhibitors of formylglycinamide ribonucleotide accumulation in Ca 755 cells than in Sa 180 cells. Similarly, 6-mercaptopurine and 6-thioguanine decreased formylglycinamide ribonucleotide accumulation to a greater extent in Ca 755 than in Sa 180 cells. The results indicate that feedback-type inhibition ofde novo purine synthesis is more pronounced in Ca 755 than in Sa 180 cells in culture.
Fibreoptic bronchoscopic electrosurgery under local anaesthesia for rapid palliation in patients with central airway malignancies: a preliminary report.
Authors: G Sutedja, K van Kralingen, F M Schramel, P E Postmus
Journal: Thorax (1994)

Obstruction of a major airway by tumour causes serious morbidity. There is still scope for a widely applicable, simple and effective treatment to provide rapid palliation.A fibreoptic bronchoscope prototype with an insulated inner sheath was used under local anaesthesia in 17 patients with locally advanced tracheobronchial malignancies. An insulated flexible electro-surgery probe was used to coagulate intraluminal tumour mass using standard electrosurgery equipment.Immediate reopening of the airway was obtained in 15 of the 17 patients. Two appeared to have extraluminal disease. Eleven patients had an obvious bronchoscopic response in whom a > 75% reopening of the normal airway diameter was achieved. Eight patients had subjective improvement of their dyspnoea, but only in four cases was there an objective improvement in physiological parameters. Haemoptysis resolved in four. There were no deaths resulting from treatment. Minor bleeding occurred in one patient and an aspiration pneumonia occurred in one. Three patients received additional treatment.Fibreoptic bronchoscopic electrosurgery is a simple technique for rapid palliation and immediate tumour debulking in patients with central tracheobronchial tumours. Further work is needed to compare its efficacy with other techniques.