tbuckley/cabot-search huggingface dataset:
Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial
Authors: Jane F. Apperley, Jorge E. Cortes, Dong-Wook Kim, Lydia Roy, Gail J. Roboz, Gianantonio Rosti, Eduardo O. Bullorsky, Elisabetta Abruzzese, Andreas Hochhaus, Dominik Heim, Carmino A. de Souza, Richard A. Larson, Jeffrey H. Lipton, H. Jean Khoury, Hyeoung-Joon Kim, Christian Sillaber, Timothy P. Hughes, Philipp Erben, Jan Van Tornout, Richard M. Stone
Journal: Journal of Clinical Oncology (2009)

Purpose Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. Patients and Methods Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). Conclusion Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
Salt-sensitive hypertension in circadian clock–deficient Cry-null mice involves dysregulated adrenal Hsd3b6
Authors: Masao Doi, Yukari Takahashi, Rie Komatsu, Fumiyoshi Yamazaki, Hiroyuki Yamada, Shogo Haraguchi, Noriaki Emoto, Yasushi Okuno, Gozoh Tsujimoto, Akihiro Kanematsu, Osamu Ogawa, Takeshi Todo, Kazuyoshi Tsutsui, Gijsbertus T J van der Horst, Hitoshi Okamura
Journal: Nature Medicine (2009)
A clustering of epidural abscesses in chronic hemodialysis patients
Authors: E C Kovalik, J R Raymond, F J Albers, M Berkoben, D W Butterly, B Montella, P J Conlon
Journal: Journal of the American Society of Nephrology (1996)

The objective of this study was to investigate factors that might increase the risk of epidural abscesses in hemodialysis patients. The charts of all hemodialysis patients presenting with an epidural abscess over a period of 5 yr at Duke University Hospital and the Durham Veterans Administration Medical Center were reviewed for patient demographics, months on dialysis, vascular access, recently treated infections, signs and symptoms at presentation, and results of any surgical intervention. Ten patients developed an epidural abscess during a 5-yr period. Severe, debilitating back pain was the only consistent initial complaint. Eight patients had dual-lumen intravenous catheters for hemodialysis access, and five patients had or were receiving parenteral antibiotics for catheter salvage. There were no consistent physical, clinical, or laboratory findings. Surgical drainage of the abscess with removal of the hemodialysis catheters and parenteral antibiotics were required for cure in six patients. It was concluded that attempts at catheter salvage with parenteral antibiotics has significant risks for complications. Hemodialysis patients with recently treated or ongoing bacteremia who complain about severe and debilitating back pain with or without neurologic findings should raise the suspicion of an occult epidural abscess.
Microdomain Switch of cGMP-Regulated Phosphodiesterases Leads to ANP-Induced Augmentation of β-Adrenoceptor-Stimulated Contractility in Early Cardiac Hypertrophy
Authors: Ruwan K. Perera, Julia U. Sprenger, Julia H. Steinbrecher, Daniela Hübscher, Stephan E. Lehnart, Marco Abesser, Kai Schuh, Ali El-Armouche, Viacheslav O. Nikolaev
Journal: Circulation Research (2015)

Cyclic nucleotides are second messengers that regulate cardiomyocyte function through compartmentalized signaling in discrete subcellular microdomains. However, the role of different microdomains and their changes in cardiac disease are not well understood.To directly visualize alterations in β-adrenergic receptor-associated cAMP and cGMP microdomain signaling in early cardiac disease.Unexpectedly, measurements of cell shortening revealed augmented β-adrenergic receptor-stimulated cardiomyocyte contractility by atrial natriuretic peptide/cGMP signaling in early cardiac hypertrophy after transverse aortic constriction, which was in sharp contrast to well-documented β-adrenergic and natriuretic peptide signaling desensitization during chronic disease. Real-time cAMP analysis in β1- and β2-adrenergic receptor-associated membrane microdomains using a novel membrane-targeted Förster resonance energy transfer-based biosensor transgenically expressed in mice revealed that this unexpected atrial natriuretic peptide effect is brought about by spatial redistribution of cGMP-sensitive phosphodiesterases 2 and 3 between both receptor compartments. Functionally, this led to a significant shift in cGMP/cAMP cross-talk and, in particular, to cGMP-driven augmentation of contractility in vitro and in vivo.Redistribution of cGMP-regulated phosphodiesterases and functional reorganization of receptor-associated microdomains occurs in early cardiac hypertrophy, affects cGMP-mediated contractility, and might represent a previously not recognized therapeutically relevant compensatory mechanism to sustain normal heart function.
Concerted gene recruitment in early plant evolution
Authors: Jinling Huang, J Peter Gogarten
Journal: Genome biology (2008)

Abstract Background Horizontal gene transfer occurs frequently in prokaryotes and unicellular eukaryotes. Anciently acquired genes, if retained among descendants, might significantly affect the long-term evolution of the recipient lineage. However, no systematic studies on the scope of anciently acquired genes and their impact on macroevolution are currently available in eukaryotes. Results Analyses of the genome of the red alga Cyanidioschyzon identified 37 genes that were acquired from non-organellar sources prior to the split of red algae and green plants. Ten of these genes are rarely found in cyanobacteria or have additional plastid-derived homologs in plants. These genes most likely provided new functions, often essential for plant growth and development, to the ancestral plant. Many remaining genes may represent replacements of endogenous homologs with a similar function. Furthermore, over 78% of the anciently acquired genes are related to the biogenesis and functionality of plastids, the defining character of plants. Conclusion Our data suggest that, although ancient horizontal gene transfer events did occur in eukaryotic evolution, the number of acquired genes does not predict the role of horizontal gene transfer in the adaptation of the recipient organism. Our data also show that multiple independently acquired genes are able to generate and optimize key evolutionary novelties in major eukaryotic groups. In light of these findings, we propose and discuss a general mechanism of horizontal gene transfer in the macroevolution of eukaryotes.
X-Linkage in Manic-Depressive Illness
Authors: R J Cadoret, G Winokur
Journal: Annual Review of Medicine (1975)

Postpartum depression (PPD) is common, disabling, and treatable. The strongest risk factor is a history of mood or anxiety disorder, especially having active symptoms during pregnancy. As PPD is one of the most common complications of childbirth, it is ...Read More
Screening for Sudden Cardiac Death in the Young
Authors: Jonathan R. Kaltman, Paul D. Thompson, John Lantos, Charles I. Berul, Jeffrey Botkin, Joshua T. Cohen, Nancy R. Cook, Domenico Corrado, Jonathan Drezner, Kevin D. Frick, Stuart Goldman, Mark Hlatky, Prince J. Kannankeril, Laurel Leslie, Silvia Priori, J. Philip Saul, Carrie K. Shapiro-Mendoza, David Siscovick, Victoria L. Vetter, Robin Boineau, Kristin M. Burns, Richard A. Friedman
Journal: Circulation (2011)

udden cardiac death (SCD) in the young (SCDY) has a devastating impact on families, care providers, and the community and attracts significant public and media attention.Sudden cardiac death is defined as an abrupt and unexpected death due to a cardiovascular cause, typically occurring Ͻ1 hour from the onset of symptoms.Depending on the source, "young" is variably defined as those less than 25, 30, 35, or 40 years of age.][3] Sudden infant death syndrome (SIDS) may be related to SCD in some infants.Sudden infant death syndrome is defined as the sudden death of an infant Ͻ1 year of age that cannot be explained after a thorough investigation is conducted, including an autopsy, death scene evaluation, and review of the clinical history.The incidence of SIDS ranges from 50 to 100 in 100 000, 4 and emerging data suggest that as many as 10% to 15% of SIDS deaths are associated with functional cardiac ion channelopathy gene variants. 5he most common diagnoses that increase risk for SCDY include hypertrophic cardiomyopathy (HCM), coronary artery anomalies of wrong sinus origin, myocarditis, arrhythmogenic right ventricular cardiomyopathy, and ion channelopathies. 6The latter category includes hereditary diseases such as the congenital long-QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome, among other less common channelopathies.These diseases are typically undetected before the SCD event.Estimated prevalence
Antiretroviral Drug–Based Microbicides to Prevent HIV-1 Sexual Transmission
Authors: Per Johan Klasse, Robin Shattock, John P. Moore
Journal: Annual Review of Medicine (2007)

The development of a vaginal (and perhaps a rectal) microbicide would be of major benefit for slowing the global spread of human immunodeficiency virus type 1 (HIV-1). A microbicide is a gel or related device that, when inserted vaginally or rectally, acts to prevent infection of a woman or a man by HIV-1 during sexual intercourse. A practical microbicide must be not only effective, safe, and user-friendly but also economically affordable in the developing world. To date, the performance of microbicide candidates in efficacy trials has been disappointing, but next-generation concepts now in or approaching clinical trials offer improved prospects for efficacy. The most plausible approaches involve topical application of antiretroviral agents with specific activity against HIV-1, compounds similar to drugs used to treat HIV-1 infection. How these inhibitors are applied may also be critical, with sustained-release formulations and vaginal ring delivery systems now becoming a high priority.
Nursing-home-acquired pneumonia in Germany: an 8-year prospective multicentre study
Authors: Santiago Ewig, Benjamin Klapdor, Mathias W Pletz, Gernot Rohde, Hartwig Schütte, Tom Schaberg, Torsten T Bauer, Tobias Welte
Journal: Thorax (2011)

<h3>Objective</h3> To determine differences in aetiologies, initial antimicrobial treatment choices and outcomes in patients with nursing-home-acquired pneumonia (NHAP) compared with patients with community-acquired pneumonia (CAP), which is a controversial issue. <h3>Methods</h3> Data from the prospective multicentre Competence Network for Community-acquired pneumonia (CAPNETZ) database were analysed for hospitalised patients aged ≥65 years with CAP or NHAP. Potential differences in baseline characteristics, comorbidities, physical examination findings, severity at presentation, initial laboratory investigations, blood gases, microbial investigations, aetiologies, antimicrobial treatment and outcomes were determined between the two groups. <h3>Results</h3> Patients with NHAP presented with more severe pneumonia as assessed by CRB-65 (confusion, respiratory rate, blood pressure, 65 years and older) score than patients with CAP but received the same frequency of mechanical ventilation and less antimicrobial combination treatment. There were no clinically relevant differences in aetiology, with <i>Streptococcus pneumoniae</i> the most important pathogen in both groups, and potential multidrug-resistant pathogens were very rare (&lt;5%). Only <i>Staphylococcus aureus</i> was more frequent in the NHAP group (n=12, 2.3% of the total population, 3.1% of those with microbial sampling compared with 0.7% and 0.8% in the CAP group, respectively). Short-term and long-term mortality in the NHAP group was higher than in the CAP group for patients aged ≥65 years (26.6% vs 7.2% and 43.8% vs 14.6%, respectively). However, there was no association between excess mortality and potential multidrug-resistant pathogens. <h3>Conclusions</h3> Excess mortality in patients with NHAP cannot be attributed to a different microbial pattern but appears to result from increased comorbidities, and consequently, pneumonia is frequently considered and managed as a terminal event.
Structural and Phylogenetic Analysis of TRAS, Telomeric Repeat-Specific Non-LTR Retrotransposon Families in Lepidopteran Insects
Authors: Yoko Kubo, Satoshi Okazaki, Tomohiro Anzai, Haruhiko Fujiwara
Journal: Molecular Biology and Evolution (2001)

TRAS1 is a non-LTR retrotransposon inserted specifically into the telomeric repeat (TTAGG)(n) in the silkworm, Bombyx mori. To characterize the evolutionary origin of TRAS-like elements, we identified seven TRAS families (TRAS3, TRAS4, TRAS5, TRAS6, TRASY, TRASZ, and TRASW) from B. mori and four elements from two Lepidoptera, Dictyoploca japonica (TRASDJ) and Samia cynthia ricini (TRASSC3, TRASSC4, and TRASSC9). More than 2,000 copies of various Bombyx TRAS elements accumulated within (TTAGG)(n) sequences as unusual but orderly tandem repeats. The 5' and 3' regions were highly conserved within each class of Bombyx TRAS elements without truncation. This suggests that distinct classes of TRAS have been maintained independently by retrotransposition into (TTAGG)(n). The phylogenetic tree of site-specific retroelements showed that nine TRAS families in Lepidoptera constitute a single phylogenetic group that is closely related to the R1 family that inserts specifically into arthropod 28S rDNA. The higher amino acid sequence identity from endonuclease (EN) to reverse transcriptase (RT) domains between TRAS groups (about 37%-70%) than among TRAS elements and R1Bm (about 25%-30%), may reflect the presence of some DNA structure responsible for their target specificity. Sequence comparison from EN to RT domains among non-LTR elements revealed several regions conserved only within TRAS elements. We found a highly conserved region that resembles the Myb-like DNA-binding structure, between the EN and RT domains. These regions may be involved in site-specific integration of TRAS elements into the (TTAGG)(n) telomeric repeats.
Lecture Notes on Respiratory Disease
Journal: Thorax (1986)

pneumonia is rarely associated with spontaneous pneumo- thorax.8Clearly, however, we cannot be certain that the pneumothorax was not caused by the underlying disease process in our second case.The safety of fibreoptic bronchoscopy, when performed as an outpatient procedure in carefully selected patients, has been clearly documented.7 Hospital admission of patients having transbronchial biopsies is, however, recommended.'We agree with this and suggest that all patients should be assessed for the presence of delayed pneumothorax just before discharge from hospital.Patients should in addition be informed of the possibility of this complication and advised to seek medical assistance early in the event of symptoms that suggest its occurrence.
Activation of intrinsic laryngeal muscles during cough.
Authors: G Sant'Ambrogio, S T Kuna, C R Vanoye, F B Sant'Ambrogio
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

We studied the pattern of discharge of the posterior cricoarytenoid (PCA), cricothyroid (CT), thyroarytenoid (TA), and arytenoideus transversus (AR) muscles during cough in 12 anesthetized dogs. Diaphragm electromyographic (EMG) activity was also recorded, together with subglottic and esophageal pressures. Trains of repetitive coughs were induced by mechanically stimulating the tracheobronchial airway. Trials with the upper airway isolated from and connected to the lower airway were performed before and following bilateral sectioning of the internal branch of the superior laryngeal nerve (SLN). The immediate effect of tracheal stimulation was an "apneic" period at FRC, during which the PCA, a laryngeal abductor, showed a progressive increase in activity accompanied by small, variable increases in the activity of the CT and the laryngeal adductors, the TA and AR. The subsequent cough efforts were divided into three phases: inspiration, glottic narrowing, and forced expiration. PCA activity was greatest during the inspiratory phase and CT activity was greatest during the expiratory phase. Peak subglottic pressure occurred during glottic narrowing and coincided with the greatest activation of the TA and AR during the cough effort, and suppression of the PCA and CT. The patterns of EMG activation were not affected by the route of breathing or SLN section. The results suggest the presence of a uniquely central process controlling laryngeal muscles during cough, independent of laryngeal sensory feedback.
Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study
Authors: Chantal BEM Reusken, Bart L Haagmans, Marcel A Müller, Carlos Gutierrez, Gert-Jan Godeke, Benjamin Meyer, Doreen Muth, V Stalin Raj, Laura Smits-De Vries, Victor M Corman, Jan-Felix Drexler, Saskia L Smits, Yasmin E El Tahir, Rita De Sousa, Janko van Beek, Norbert Nowotny, Kees van Maanen, Ezequiel Hidalgo-Hermoso, Berend-Jan Bosch, Peter Rottier, Albert Osterhaus, Christian Gortázar-Schmidt, Christian Drosten, Marion PG Koopmans
Journal: The Lancet Infectious Diseases (2013)
Phase III Study of Concurrent Versus Sequential Thoracic Radiotherapy in Combination With Cisplatin and Etoposide for Limited-Stage Small-Cell Lung Cancer: Results of the Japan Clinical Oncology Group Study 9104
Authors: Minoru Takada, Masahiro Fukuoka, Masaaki Kawahara, Takahiko Sugiura, Akira Yokoyama, Soichiro Yokota, Yutaka Nishiwaki, Koshiro Watanabe, Kazumasa Noda, Tomohide Tamura, Haruhiko Fukuda, Nagahiro Saijo
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To evaluate the optimal timing for thoracic radiotherapy (TRT) in limited-stage small-cell lung cancer (LS-SCLC), the Lung Cancer Study Group of the Japan Clinical Oncology Group conducted a phase III study in which patients were randomized to sequential TRT or concurrent TRT. PATIENTS AND METHODS: We treated 231 patients with LS-SCLC. TRT consisted of 45 Gy over 3 weeks (1.5 Gy twice daily), and the patients were randomly assigned to receive either sequential or concurrent TRT. All patients received four cycles of cisplatin plus etoposide every 3 weeks (sequential arm) or 4 weeks (concurrent arm). TRT was begun on day 2 of the first cycle of chemotherapy in the concurrent arm and after the fourth cycle in the sequential arm. RESULTS: Concurrent radiotherapy yielded better survival than sequential radiotherapy (P = .097 by log-rank test). The median survival time was 19.7 months in the sequential arm versus 27.2 months in the concurrent arm. The 2-, 3-, and 5-year survival rates for patients who received sequential radiotherapy were 35.1%, 20.2%, and 18.3%, respectively, as opposed to 54.4%, 29.8% and 23.7%, respectively, for the patients who received concurrent radiotherapy. Hematologic toxicity was more severe in the concurrent arm. However, severe esophagitis was infrequent in both arms, occurring in 9% of the patients in the concurrent arm and 4% in the sequential arm. CONCLUSION: This study strongly suggests that cisplatin plus etoposide and concurrent radiotherapy is more effective for the treatment of LS-SCLC than cisplatin plus etoposide and sequential radiotherapy.
Volumetric Aerobiological Survey of Conidial Fungi in the North‐East Netherlands
Authors: F. Beaumont, H. F. Kauffman, J. G. R. de Monchy, H. J. Sluiter, K. de Vries
Journal: Allergy (1985)

A study was undertaken to see whether the principal airborne fungi in the North‐East Netherlands were also found to be the most reactive in skin testing. Atmospheric samples were taken weekly with the Andersen sampler, from April 1981, up to and including, June 1983, At the same time skin tests of 833 patients referred to the outpatient Departments of Pulmonology and Allergology, because of recurrent bronchial obstructive complaints and a suspected allergy, were studied for strongly positive skin reactivity to fungi. 4.6% of the patients reacted with a wheal of 10 mm diameter or more to one or more of the tested fungi. Almost three‐quarters of the airborne fungal “flora” was composed of seven genera, namely (in order of occurrence); 1) Cladosporium (42,6 %), 2) Botrytis (8.6 %), 3) Yeasts (7 %), 4) Penicillium (5.8%), 5) Basidiomycetes (5.7%), 6) Aspergillus (3.7%), and 7) Altenaria (0.9%), In skin‐testing, however, a different order of occurrence existed; namely: 1) Beauveria (6.8%), 2) Botrytis (6.1%), 3) Aspergillus (4.7%), 4) Mucor (3.8%), 5) Epicoccum (3%), 6) Cladosporium (2.3%), and 7) Altenaria (1.1%), It is concluded that the most prevailing airborne moulds are not necessarily the most potent allergens, at least in skin testing. Aspergillus and Botrytis showed a high sensitization rate, while Cladosporium and Altenaria did not. Botrytis deserves further study because of its frequent airborne occurrence and marked allergenic properties.
Dual activation of STAT-3 and Akt is required during the trigger phase of ischaemic preconditioning
Authors: N. Suleman, S. Somers, R. Smith, L. H. Opie, S. C. Lecour
Journal: Cardiovascular Research (2008)

During preconditioning by tumour necrosis factor-alpha (TNFalpha), activation of the signal transducer and activator of transcription-3 (STAT-3) but not Akt, is essential, whereas ischaemic cardiac preconditioning (IPC) requires both STAT-3 and Akt at the time of reperfusion. However, it is not known whether the same signalling pattern occurs during the preconditioning stimulus (trigger phase) and whether links exist between STAT-3 and Akt. Hence, our hypothesis is that concomitant activation or co-interaction between these two key signals is required during the trigger phase for IPC. Conversely, we proposed that there would be no such interaction when preconditioning was induced by TNFalpha (TNF-PC).Cardiomyocytes, isolated from adult wild-type (WT) and cardiac-specific STAT-3 knockout (KO) mice, were exposed to simulated ischaemia (SI) reperfusion. Cells were preconditioned either by 30 min SI or by 30 min TNFalpha (0.5 ng/mL) in the presence or absence of AG490 (100 nM) or wortmannin (100 nM) to inhibit STAT-3 or Akt, respectively. Cell viability was evaluated by trypan blue, and phosphorylation levels of STAT-3 and Akt were measured by Western blot analysis. Similar experiments were conducted in isolated rat hearts subjected to an ischaemia-reperfusion insult. Both preconditioning stimuli failed to protect KO cardiomyocytes, and addition of AG490 abolished preconditioning in WT cardiomyocytes or isolated hearts. Wortmannin abolished the protection afforded by IPC, but did not affect TNF-PC in both models. Western blot analysis demonstrated that added wortmannin during IPC stimulus decreased STAT-3 phosphorylation while, conversely, AG490 reduced Akt phosphorylation.STAT-3 activation could be achieved independent of Akt during TNF-PC. In contrast, during an IPC stimulus, both prosurvival signalling molecule cascades acted in concert so that inhibiting activation of STAT-3 also inhibited that of Akt and vice versa.