tbuckley/cabot-search huggingface dataset:
Adult gliosarcoma: epidemiology, natural history, and factors associated with outcome
Authors: Kevin R. Kozak, Anand Mahadevan, John S. Moody
Journal: Neuro-Oncology (2008)

The epidemiology and natural history of adult gliosarcomas (GSMs), as well as patient and treatment factors associated with outcome, are ill defined. Patients over 20 years of age with GSM diagnosed from 1988 to 2004 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier survival analysis and Cox models were used to examine outcomes. Similar analyses were conducted for patients diagnosed with glioblastoma (GBM) over the same time period. GSM represented 2.2% of the 16,388 patients identified with either GSM or GBM. No significant differences between GSM and GBM were identified with respect to age, gender, race, tumor size, or use of adjuvant radiation therapy (RT). Patients with GSM were more likely to have temporal lobe involvement and undergo some form of tumor resection. The most important analyzed factors influencing GSM overall survival were age, extent of resection, and use of adjuvant RT. After adjusting for factors impacting overall survival, the prognosis for GSM appears slightly worse than for GBM (HR = 1.17, 95% CI, 1.05-1.31). GSM is a rare malignancy that presents very similarly to GBM with a slightly greater propensity for temporal lobe involvement. Optimal treatment remains to be defined. However, these retrospective findings suggest tumor excision, as opposed to biopsy only, and adjuvant RT may improve outcome. Despite therapy, prognosis remains dismal and outcomes may be inferior to those seen in GBM patients.
A Fatal Trip with Ecstasy: A Case of 3,4-Methylene-Dioxymethamphetamine/ 3,4-Methylenedioxy-Amphetamine Toxicity
Authors: J R Coore
Journal: Journal of the Royal Society of Medicine (1996)

Since the late 1980s there have been a number of reports about the complications associated with using the designer drug 3,4-methylenedioxymeth-amphetamine (MDMA) or ‘ecstasy’ 1-3 . Although this drug has been widely abused in the past, the potentially fatal complications have arisen recently mainly due to the circumstances of its use at all-night dance sessions or ‘raves’. A combination of direct toxicity and strenuous physical exertion can lead to hyperthermia and its attendant complications. The following case illustrates some of the possible consequences following ingestion of ‘ecstasy’, and reiterates the importance of prompt recognition and treatment in preventing the development of irreversible sequelae.
Evolution of the Xenopus piggyBac Transposon Family TxpB: Domesticated and Untamed Strategies of Transposon Subfamilies
Authors: Akira Hikosaka, Toshihiro Kobayashi, Yumiko Saito, Akira Kawahara
Journal: Molecular Biology and Evolution (2007)

A new family, termed TxpB, of DNA transposons belonging to the piggyBac superfamily was found in 3 Xenopus species (Xenopus tropicalis, Xenopus laevis, and Xenopus borealis). Two TxpB subfamilies of Kobuta and Uribo1 were found in all the 3 species, and another subfamily termed Uribo2 was found in X. tropicalis. Molecular phylogenetic analyses of their open reading frames (ORFs) revealed that TxpB transposons have been maintained for over 100 Myr. Both the Uribo1 and the Uribo2 ORFs were present as multiple copies in each genome, and some of them were framed by terminal inverted repeat sequences. In contrast, all the Kobuta ORFs were present as a single copy in each genome and exhibited high evolutionary conservation, suggesting domestication of Kobuta genes by the host. Genomic insertion polymorphisms of the Uribo1 and Uribo2 transposons (nonautonomous type) were observed in a single species of X. tropicalis, indicating recent transposition events. Transfection experiments in cell culture revealed that an expression vector construct for the intact Uribo2 ORF caused precise excision of a nonautonomous Uribo2 element from the target vector construct but that for the Kobuta ORF did not. The present results support our viewpoint that some Uribo2 members are naturally active autonomous transposons, whereas Kobuta members may be domesticated by hosts.
Increased Medial Orbitofrontal and Amygdala Activation: Evidence for a Systems-Level Endophenotype of Bipolar I Disorder
Authors: Julia Linke, Andrea Victoria King, Marcella Rietschel, Jana Strohmaier, Michael Hennerici, Achim Gass, Andreas Meyer-Lindenberg, Michèle Wessa
Journal: American Journal of Psychiatry (2012)

Bipolar I disorder is highly heritable, but endophenotypes of the disorder mediating genetic risk are only beginning to be defined. The authors investigate state- and trait-related neural mechanisms related to motivation in euthymic bipolar patients and unaffected first-degree relatives of bipolar patients to define the status of motivational processing as a neural systems-level endophenotype. Our study comprised two samples; the first consisted of 19 euthymic bipolar patients and 19 matched comparison subjects, and the second included 22 relatives and 22 matched comparison subjects. Motivational processing was assessed with a probabilistic reversal learning task during event-related functional MRI. Data were analyzed using a region-of-interest approach restricting analysis to the medial and lateral orbitofrontal cortex, the amygdala, the anterior cingulate cortex, and the striatum. The authors observed increased activation in response to reward and reward reversal contingencies in the left medial orbitofrontal cortex in patients with bipolar disorder and in the right medial orbitofrontal cortex in their relatives. Activation of the amygdala in response to reward reversal was increased in patients and relatives. In response to reward, activation of the amygdala was greater only in relatives, but there was a significant negative correlation between medication and amygdala activation in patients. These results identify increased activity of the orbitofrontal cortex and the amygdala, related to heightened sensitivity to reward and deficient prediction error signal, as a candidate endophenotype of bipolar disorder. The results support a role of motivational processing in the risk architecture of bipolar disorder and identify a new systems-level therapeutic target for the illness.
Dysphagia following fish bone ingestion
Authors: Y.-Y. Chen, H.-H. Yen, C.-D. Yao, C.-W. Yang, M.-S. Soon, H.-K. Wu
Journal: Gut (2007)

A 43-year-old woman was admitted to our emergency department with dysphagia and chest pain that developed soon after swallowing a fish bone. Her medical history was unremarkable as …
Dendritic cell subsets in blood and lymphoid tissue of rhesus monkeys and their mobilization with Flt3 ligand
Authors: P. Toby H. Coates, Simon M. Barratt-Boyes, Linyou Zhang, Vera S. Donnenberg, Peta J. O'Connell, Alison J. Logar, F. Jason Duncan, Michael Murphey-Corb, Albert D. Donnenberg, Adrian E. Morelli, Charles R. Maliszewski, Angus W. Thomson
Journal: Blood (2003)
Susceptibility to type 1 autoimmune hepatitis is associated with shared amino acid sequences at positions 70–74 of the HLA-DRB1 molecule
Authors: Young-Suk Lim, Heung-Bum Oh, Sung-Eun Choi, Oh-Joong Kwon, Yong-Seok Heo, Han Chu Lee, Dong Jin Suh
Journal: Journal of Hepatology (2007)
Therapy of murine leukemia with monoclonal antibody against a normal differentiation antigen.
Authors: C C Badger, I D Bernstein
Journal: The Journal of Experimental Medicine (1983)

The ability of monoclonal antibodies against the Thy-1.1 differentiation antigen to inhibit the growth of transplanted syngeneic AKR/J SL2 leukemic cells has been previously demonstrated. In the present study we further examined therapy with monoclonal antibody of the IgG2a isotype, which was the most effective isotype studied. Intravenous infusion of ascites fluid containing the anti-Thy-1.1 monoclonal antibody 19-E12 1-2 h after tumor implantation led to inhibition of the growth of 3 X 10(5) but not 3 X 10(6) syngeneic SL2 leukemic cells. The achievement of the maximal therapeutic effect required the infusion of a dose containing 3.2 mg of antibody, which inhibited the growth of a subcutaneous inoculum of 3 X 10(5) SL2 leukemic cells in 83% of treated mice. Multiple doses of antibody were no more effective than a single dose given shortly after tumor implantation. The infusion of this relatively large 3.2-mg dose of antibody was required to infiltrate the subcutaneous space and saturate surface Thy-1.1 sites on leukemic cells in a subcutaneous tumor nodule. The failure of antibody to inhibit larger numbers of tumor cells was investigated. Growth of a subcutaneous tumor nodule in mice challenged with more than 3 X 10(5) cells resulted from the growth of Thy-1.1-bearing cells in spite of the presence of the infused anti-Thy-1.1 antibody on their surfaces. In contrast, metastatic growth was due to the emergence of variant leukemic cells lacking the Thy-1.1 antigen. Thus, treatment of transplanted T leukemic cells with an IgG2a anti-Thy-1.1 monoclonal antibody was effective in eliminating 3 X 10(5) antigen-bearing leukemic cells from the subcutaneous space and was very effective in preventing metastasis of leukemic cells expressing the target Thy-1.1 antigen. Therapy was limited by the failure of host mechanisms to eliminate larger numbers of subcutaneous leukemic cells coated with the infused antibody and by the emergence of variant leukemic cells lacking the target antigen.
Tumor necrosis factor/cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis.
Authors: P F Piguet, M A Collart, G E Grau, Y Kapanci, P Vassalli
Journal: The Journal of Experimental Medicine (1989)

The role of TNF-alpha/cachectin in the pneumopathy elicited by bleomycin has been investigated. After a single intratracheal bleomycin instillation, an increase of the lung TNF-alpha mRNA level was evident, from days 5 to 15, as shown by Northern gel analysis of whole lung RNA. In contrast, lung IL-1-alpha and GM-CSF mRNA were not detectable. In mice passively immunized with rabbit anti-mouse TNF-alpha IgG, the bleomycin-induced collagen deposition, evaluated by the total lung hydroxyproline assay on day 15, was prevented. Depletion of the CD4 and CD8 T lymphocytes by an in vivo treatment with mAb prevented the bleomycin-induced increase of TNF mRNA level and fibrosis. After an administration of bleomycin in continuous intraperitoneal perfusion, the diffuse alveolar damage observed by light and electron microscopy was almost completely prevented by anti-TNF antibody. These results indicate that in response to bleomycin, the T lymphocytes induce, by an undefined mechanism, an increase of the pulmonary TNF production, which leads to alveolar damage, growth of fibroblast, and collagen deposition.
Talin is required for integrin-mediated platelet function in hemostasis and thrombosis
Authors: Brian G. Petrich, Patrizia Marchese, Zaverio M. Ruggeri, Saskia Spiess, Rachel A.M. Weichert, Feng Ye, Ralph Tiedt, Radek C. Skoda, Susan J. Monkley, David R. Critchley, Mark H. Ginsberg
Journal: The Journal of Experimental Medicine (2007)

Integrins are critical for hemostasis and thrombosis because they mediate both platelet adhesion and aggregation. Talin is an integrin-binding cytoplasmic adaptor that is a central organizer of focal adhesions, and loss of talin phenocopies integrin deletion in Drosophila. Here, we have examined the role of talin in mammalian integrin function in vivo by selectively disrupting the talin1 gene in mouse platelet precursor megakaryocytes. Talin null megakaryocytes produced circulating platelets that exhibited normal morphology yet manifested profoundly impaired hemostatic function. Specifically, platelet-specific deletion of talin1 led to spontaneous hemorrhage and pathological bleeding. Ex vivo and in vitro studies revealed that loss of talin1 resulted in dramatically impaired integrin αIIbβ3-mediated platelet aggregation and β1 integrin–mediated platelet adhesion. Furthermore, loss of talin1 strongly inhibited the activation of platelet β1 and β3 integrins in response to platelet agonists. These data establish that platelet talin plays a crucial role in hemostasis and provide the first proof that talin is required for the activation and function of mammalian α2β1 and αIIbβ3 integrins in vivo.
Phase I Clinical Pharmacology Study of F14512, a New Polyamine-Vectorized Anticancer Drug, in Naturally Occurring Canine Lymphoma
Authors: Dominique Tierny, François Serres, Zacharie Segaoula, Ingrid Bemelmans, Emmanuel Bouchaert, Aurélie Pétain, Viviane Brel, Stéphane Couffin, Thierry Marchal, Laurent Nguyen, Xavier Thuru, Pierre Ferré, Nicolas Guilbaud, Bruno Gomes
Journal: Clinical Cancer Research (2015)

F14512 is a new topoisomerase II inhibitor containing a spermine moiety that facilitates selective uptake by tumor cells and increases topoisomerase II poisoning. F14512 is currently in a phase I/II clinical trial in patients with acute myeloid leukemia. The aim of this study was to investigate F14512 potential in a new clinical indication. Because of the many similarities between human and dog lymphomas, we sought to determine the tolerance, efficacy, pharmacokinetic/pharmacodynamic (PK/PD) relationship of F14512 in this indication, and potential biomarkers that could be translated into human trials.Twenty-three dogs with stage III-IV naturally occurring lymphomas were enrolled in the phase I dose-escalation trial, which consisted of three cycles of F14512 i.v. injections. Endpoints included safety and therapeutic efficacy. Serial blood samples and tumor biopsies were obtained for PK/PD and biomarker studies.Five dose levels were evaluated to determine the recommended dose. F14512 was well tolerated, with the expected dose-dependent hematologic toxicity. F14512 induced an early decrease of tumoral lymph node cells, and a high response rate of 91% (21/23) with 10 complete responses, 11 partial responses, 1 stable disease, and 1 progressive disease. Phosphorylation of histone H2AX was studied as a potential PD biomarker of F14512.This trial demonstrated that F14512 can be safely administered to dogs with lymphoma resulting in strong therapeutic efficacy. Additional evaluation of F14512 is needed to compare its efficacy with standards of care in dogs, and to translate biomarker and efficacy findings into clinical trials in humans.
Psychological and social aspects of pregnancy, childbirth and early parenting after assisted conception: a systematic review
Authors: K. Hammarberg, J.R.W. Fisher, K.H. Wynter
Journal: Human Reproduction Update (2008)

It is known that infertility affects emotional well-being, satisfaction with life and self-esteem and that failed assisted reproductive technology (ART) treatment is associated with diminished life satisfaction, reduced self-confidence and substantial psychological distress. Investigations of whether these persist when treatment results in a pregnancy and live birth have been undertaken. A systematic search for English-language research articles on psychological and social aspects of pregnancy, childbirth and the first post-partum year after ART conception. Of 466 retrieved papers, 46 met inclusion criteria. These reported data from 28 studies. There is consistent evidence that marital satisfaction, emotional well-being and self-regard in pregnancy, attachment to the fetus and parent–infant relationship in ART groups are similar to comparison groups. Anxiety about the survival of the fetus and early parenting difficulties appear to be higher and post-natal self-confidence lower. Evidence about adjustment to pregnancy and parenthood and the experience of childbirth is inconclusive and reports of parental perceptions of infant temperament and behaviour are contradictory. Between-study methodological differences may explain the lack of consistency in findings of the influence of infertility and ART on some aspects of the transition to parenthood. Overall, this body of evidence is best described as emergent. It is possible that in pregnancy after ART, parenthood might be idealized and this might then hinder adjustment and the development of a confident parental identity.
Controlled-analysis of the effects of inhaled lignocaine in exercise-induced asthma.
Authors: M P Griffin, E R McFadden, R H Ingram, S Pardee
Journal: Thorax (1982)

To determine whether anaesthesia of the intrathoracic airways would attenuate the development of exercise-induced asthma, we studied eight symptomless asthmatic patients by cycle ergometry after saline or lignocaine pretreatment while they were breathing air at 24 degrees C with 9.1 mg of H2O/l. Pulmonary mechanics were measured before and after the administration of each agent, and again five minutes after cessation of exercise. Sufficient lignocaine was administered to abolish the gag reflex and the cough response to aerosols of citric acid. Before exercise there were no significant differences for any lung function variable between the saline and lignocaine results. Equally, there were no significant differences between these agents for minute ventilation (VE) during exercise (VE lignocaine = 71.0 +/- 7.4 (SEM) l/min; VE saline 67.2 +/- 8.1 l/min;), or in the severity of the subsequent bronchospastic response (for example, the FEV1 with saline was 22.6 +/- 2.9% decrease, and with lignocaine 23.6 +/- 8.5%). Thus these results do not support the idea that there are thermally sensitive neural receptors in intrathoracic airways that play a role in the pathogenesis of exercise-induced asthma.
Vasoactive intestinal peptide receptor in failing human ventricular myocardium exhibits increased affinity and decreased density.
Authors: R E Hershberger, F L Anderson, M R Bristow
Journal: Circulation Research (1989)

We investigated vasoactive intestinal peptide (VIP)-receptor pharmacology in failing and nonfailing human ventricular myocardium by examining [125I]VIP binding in membrane fractions of left ventricle and inotropic effects of VIP in isolated right ventricular trabeculae mounted in tissue baths. [125I]VIP binding demonstrated upwardly concave, curvilinear Scatchard plots consistent with two classes of binding sites. Only the high-affinity (dissociation constant [Kd] 400-800 pM) site could be regulated by guanine nucleotides. Compared with nonfailing heart, membranes derived from failing heart exhibited a twofold reduction in the Kd of the high-affinity VIP binding site, whereas the receptor density (Bmax) was decreased by 62%. In concordance with this decreased receptor density and increased affinity, the maximal contractile response of right ventricular trabeculae from failing right ventricles was decreased by 61%, and the dose-response curve to VIP was left-shifted approximately threefold. We conclude that the VIP receptor in failing human ventricular myocardium exhibits novel regulatory behavior consisting of increased receptor affinity and decreased receptor density.
Studies of Hemodynamic Changes in Humans Following Induction of Low and High Spinal Anesthesia
Authors: SALVATORE M. SANCETTA, R. BEVERLEY LYNN, FIORINDO A. SIMEONE, ROY W. SCOTT, GLADYS HECKMAN, HANNA JANOUSKOVEC
Journal: Circulation (1952)

After a lapse of some years, surgeons and anesthesiologists alike are re-exploring the use of high spinal anesthesia, which is designed to produce a "useful" hypotension coupled with maximal relaxation. In the present study the hemodynamic changes induced by low and high spinal anesthesia, the latter arbitrarily defined as ablation of sympathetic, sensory and somatic nerves fibers above the fourth dermatomic segment, have been investigated in a series of waking patients not undergoing surgery.
High-strength pancreatic enzymes
Authors: CarlosE. Milla, CatherineL. Wielinski, WarrenJ. Warwick, J.Alastair Innes, AndrewP. Greening, Kevin Webb, M.J. Mahony, M. Corcoran, G.L. Briars, D.M. Griffiths, I.E. Moore, P.H. Williams, K. Johnson, C.J. Rolles
Journal: The Lancet (1994)
Influence of cervical sympathetic nerves on ventilation and upper airway resistance in the rat
Authors: KD O'Halloran, AK Curran, A Bradford
Journal: European Respiratory Journal (1998)

The cervical sympathetic trunks innervate the carotid bodies, carotid baroreceptors, thyroid gland and the upper airway mucosa, structures which can influence breathing and upper airway resistance. However, their role in the control of ventilation and upper airway patency is poorly understood. A constant airflow was applied to the upper airway through a high-cervical tracheostomy in anaesthetized rats breathing spontaneously through a low-cervical tracheostomy. The peripheral ends of the cut cervical sympathetic trunks were stimulated electrically and airflow resistance and ventilation were measured. The effects of cervical sympathetic trunk section on ventilation were also measured in conscious rats. In conscious rats, cutting the sympathetic trunks caused a decrease in ventilation during normoxia but only slightly affected ventilatory responses to hypoxia and hypercapnia. In anaesthetized rats, sympathetic trunk stimulation caused an inhibition of breathing which was sometimes followed by excitation. These responses were unaffected by alpha- or beta-adrenoceptor blockade but were abolished by cutting the carotid sinus nerves. Sympathetic stimulation also caused a fall in upper airway resistance which was reduced by bypassing the nose, unaffected by propranolol or carotid sinus nerve section and abolished by phentolamine. It was concluded that the cervical sympathetic nerves exert important influences on ventilation and upper airway resistance.
Genetic Adaptation of the Hypoxia-Inducible Factor Pathway to Oxygen Pressure among Eurasian Human Populations
Authors: Lin-dan Ji, Yu-qing Qiu, Jin Xu, David M. Irwin, Siu-Cheung Tam, Nelson L.S. Tang, Ya-ping Zhang
Journal: Molecular Biology and Evolution (2012)

Research into the mechanisms of human adaptation to the hypoxic environment of high altitude is of great interest to the fields of human physiology and clinical medicine. Recently, the gene EGLN1, from the hypoxia-inducible factor (HIF) pathway, was identified as being involved in the hypoxic adaptation of highland Andeans and Tibetans. Both highland Andeans and Tibetans have adapted to an extremely hypoxic habitat and less attention has been paid to populations living in normoxic conditions at sea level and mild-hypoxic environments of moderate altitude, thus, whether a common adaptive mechanism exists in response to quantitative variations of environmental oxygen pressure over a wide range of residing altitudes is unknown. Here, we first performed a genome-wide association study of 35 populations from the Human Genome Diversity-CEPH Panel who dwell at sea level to moderate altitude in Eurasia (N = 691; 0-2,500 m) to identify the genetic adaptation profile of normoxic and mild-hypoxic inhabitants. In addition, we systematically compared the results from the present study to six previously published genome-wide scans of highland Andeans and Tibetans to identify shared adaptive signals in response to quantitative variations of oxygen pressure. For normoxic and mild-hypoxic populations, the strongest adaptive signal came from the mu opioid receptor-encoding gene (OPRM1, 2.54 × 10(-9)), which has been implicated in the stimulation of respiration, while in the systematic survey the EGLN1-DISC1 locus was identified in all studies. A replication study performed with highland Tibetans (N = 733) and sea level Han Chinese (N = 748) confirmed the association between altitude and SNP allele frequencies in OPRM1 (in Tibetans only, P < 0.01) and in EGLN1-DISC1 (in Tibetans and Han Chinese, P < 0.01). Taken together, identification of the OPRM1 gene suggests that cardiopulmonary adaptation mechanisms are important and should be a focus in future studies of hypoxia adaptation. Furthermore, the identification of the EGLN1 gene from the HIF pathway suggests a common adaptive mechanism for Eurasian human populations residing at different altitudes with different oxygen pressures.