tbuckley/cabot-search huggingface dataset:
Coagulation defects in cyclosporine a treated allogeneic bone marrow transplant patients
Authors: Roy E. Smith, Dale D. Berg
Journal: American Journal of Hematology (1988)

CSA toxicity includes renal impairment, microangiopathic hemolytic anemia (MAHA), thrombocytopenia (T), and consumptive coagulopathy (CC). We report five BMT patients who developed CSA-associated hematological toxicity. All were conditioned with Ara-C, Cyclophosphamide, Methylprednisolone, TBI, and in two cases busulfan. IV CSA was started the day after marrow infusion and, when practicable, changed to the enteral route. Five patients developed MAHA and T resulting in significantly increased transfusion requirements. All patients had renal impairment and red cell fragmentation. In all patients fragmentation was noted before renal impairment. All developed disproportionate increases in BUN relative to serum creatinine consistent with decreased renal perfusion. Hypertension followed renal impairment in four cases and occurred at the same time as the renal impairment in one case. Two developed CC, prolongation in APTT, and marked decreases in plasma fibrinogen. All patients improved on reduction of the CSA dose. BMT recipients receiving CSA at variable doses may develop evidence of a TTP-like syndrome and/or CC.
P159 Validation of the VitaloJAK™ 24 Hour Ambulatory Cough Monitor: Abstract P159 Table 1
Authors: K McGuinness, K Holt, R Dockry, J Smith
Journal: Thorax (2012)

<h3>Introduction</h3> Development of novel treatments for cough and its management are hampered by the lack of well validated objective cough frequency methodologies. Previous validations have been performed over limited time periods or in laboratory conditions not always representative of typical usage. We describe the rigorous validation of a semi-automated 24 hour ambulatory cough monitoring system (Vitalojak; Vitalograph; Buckinghamshire, England) operating in a manner which completely replicates routine practise. <h3>Methods</h3> In total 10 (4 female) patients (mean age 60.4 years [SD ±14.1] including 6 chronic cough, 2 asthma, 1 COPD and 1 healthy control underwent full 24 Hour ambulatory monitoring (VitaloJAK™). These recordings were manually counted by trained cough counters who also recorded the time at which each cough occurred. These 24 hour recordings were then compressed using custom designed compression software and the sensitivity to cough and the reduced file times were determined. Importantly in each case we confirmed that cough sounds identified in the compressed files were the same sounds identified by the trained manual cough counters in the full 24 hour recording. We tested the software algorithm using three distinct compression levels (1, 2 and 3). <h3>Results</h3> All results are presented as median (IQR). Sensitivities to cough (%) for compression levels 1, 2 and 3 are 100(100, 100), 100(99.53, 100) and 99.92(99.33, 100) and for reduced file times (minutes) 65.89 (62.40, 83.07), 43.21 (35.94, 57.23) and 26.30 (25.07,46.81) respectively (Table 1). <h3>Conclusions</h3> The vitaloJAK™ is a reliable, robust and efficient tool for the objective measurement of cough frequency. Importantly it reduces 24 hour recordings by up to 98% whilst preserving close to 100% of recorded cough sounds. This development facilitates efficient and speedy manual cough counting and the level of compression achieved represents significant progress towards fully automated cough monitoring.
Improved dendritic cell-based immunization against hepatitis C virus using peptide inhibitors of interleukin 10
Authors: Nancy Díaz-Valdés, Lorea Manterola, Virginia Belsúe, José I. Riezu-Boj, Esther Larrea, Itziar Echeverria, Diana Llópiz, Jacinto López-Sagaseta, Hervé Lerat, Jean-Michel Pawlotsky, Jesús Prieto, Juan J. Lasarte, Francisco Borrás-Cuesta, Pablo Sarobe
Journal: Hepatology (2010)

The high levels of interleukin 10 (IL-10) present in chronic hepatitis C virus (HCV) infection have been suggested as responsible for the poor antiviral cellular immune responses found in these patients. To overcome the immunosuppressive effect of IL-10 on antigen-presenting cells such as dendritic cells (DCs), we developed peptide inhibitors of IL-10 to restore DC functions and concomitantly induce efficient antiviral immune responses. Two IL-10-binding peptides (p9 and p13) were selected using a phage-displayed library and their capacity to inhibit IL-10 was assessed in a bioassay and in STAT-3 (signal transducer and activator of transcription 3) phosphorylation experiments in vitro . In cultures of human leukocytes where HCV core protein induces the production of IL-10, p13 restored the ability of plasmacytoid DC to produce interferon alpha (IFN-α) after Toll-like receptor 9 (TLR9) stimulation. Similarly, when myeloid DCs were stimulated with CD40L in the presence of HCV core, p9 enhanced IL-12 production by inhibiting HCV core-induced as well as CD40L-induced IL-10. Moreover, in vitro , p13 potentiated the effect of maturation stimuli on human and murine DC, increasing their IL-12 production and stimulatory activity, which resulted in enhanced proliferation and IFN-γ production by responding T-cells. Finally, immunization with p13-treated murine DC induced stronger anti-HCV T-cell responses not only in wildtype mice but also in HCV transgenic mice and in mice transiently expressing HCV core in the liver. Conclusion: These results suggest that IL-10 inhibiting peptides may have important applications to enhance anti-HCV immune responses by restoring the immunostimulatory capabilities of DC. (Hepatology 2011.)
Local and global dynamical control parameters are not so easily separated
Authors: David T. J. Liley
Journal: Behavioral and Brain Sciences (2000)

Hierarchical systems such as cortical tissue will indeed exhibit dynamics that are scale-dependent, but Nunez's conjecture that theoretically independent transfer functions for each level can be specified and then combined ignores the fact that, in cortex, the same excitatory neuronal populations will contribute to both local and global dynamics.
Evolutionary History of Arabidopsis thaliana Aminoacyl-tRNA Synthetase Dual-Targeted Proteins
Authors: M. M. Brandao, M. C. Silva-Filho
Journal: Molecular Biology and Evolution (2010)

Aminoacyl-transfer RNA (tRNA) synthetases (aaRS) are key players in translation and act early in protein synthesis by mediating the attachment of amino acids to their cognate tRNA molecules.In plants, protein synthesis may occur in three subcellular compartments (cytosol, mitochondria, and chloroplasts), which requires multiple versions of the protein to be correctly delivered to its proper destination.The organellar aaRS are nuclear encoded and equipped with targeting information at the N-terminal sequence, which enables them to be specifically translocated to their final location.Most of the aaRS families present organellar proteins that are dual targeted to mitochondria and chloroplasts.Here, we examine the dual targeting behavior of aaRS from an evolutionary perspective.Our results show that Arabidopsis thaliana aaRS sequences are a result of a horizontal gene transfer event from bacteria.However, there is no evident bias indicating one single ancestor (Cyanobacteria or Proteobacteria).The dual-targeted aaRS phylogenetic relationship was characterized into two different categories (paralogs and homologs) depending on the state recovered for both dual-targeted and cytosolic proteins.Taken together, our results suggest that the dual-targeted condition is a gain-of-function derived from gene duplication.Selection may have maintained the original function in at least one of the copies as the additional copies diverged.
H-2D (Rfv-1) gene influence on recovery from Friend virus leukemia is mediated by nonleukemic cells of the spleen and bone marrow.
Authors: W J Britt, B Chesebro
Journal: The Journal of Experimental Medicine (1980)

H-2D (Rfv-1)-associated control of recovery from FV leukemia was studied in congenic mice. In irradiation chimeras, the high recovery phenotype was transferred by cells of the spleen, bone marrow, and fetal liver. Furthermore, in cell transfers using unirradiated recipients, spleen and bone marrow cells of the high-recovery genotype were able to mediate recovery from leukemia in mice of the low-recovery genotype. Thus, the H-2D (Rfv-1) influence on recovery appeared to operate via nonleukemic cells of the spleen and bone marrow rather than via leukemic cells. The specific nonleukemic cell type(s) involved in recovery remains unknown. However, the mechanism appears to be complex and probably involves both anti-FV antibody and FV-specific cytotoxic T lymphocytes.
Primary Repair and Autotransplantation of Cardiac Valves
Authors: R McKay, D N Ross
Journal: Annual Review of Medicine (1993)

The aortic valve is a beautifully designed and balanced structure with precise opening and closing mechanisms. Its design probably cannot be improved upon by man-made mechanical devices, no matter how ingenious. It is logical to use human valves as replacements because of their superior structural configuration. Their chief difficulties are in the troubles of the learning curve of the surgeon to achieve a competent mechanism and the hazard of infection. The pulmonary autograft or translocation of the pulmonary valve to the aortic position offers many advantages, and the long-term results are good. Conservative repair and reconstruction of the aortic valve are increasing in popularity but have a relatively limited application. The mitral valve has a less precise and more adjustable type of mechanism and generous leaflet coaptation. These features make it more amenable to repair, as demonstrated in the clinical series of the technique. Repair is clearly preferable to replacement at present. The tricuspid valve is eminently suitable for reconstruction, but late results are not very good. The disappointing outcome, however, reflects more the severity of underlying cardiac pathology than the effectiveness of the repair.
Interleukin-11 induces Th2 polarization of human CD4+ T cells
Authors: Antonio Curti, Marina Ratta, Silvia Corinti, Giampiero Girolomoni, Francesca Ricci, Pierluigi Tazzari, Michela Siena, Alexis Grande, Miriam Fogli, Sante Tura, Roberto M. Lemoli
Journal: Blood (2001)
Sleep and daytime sleepiness in upper airway resistance syndrome compared to obstructive sleep apnoea syndrome
Authors: C. Guilleminault, Y. Do Kim, S. Chowdhuri, M. Horita, M. Ohayon, C. Kushida
Journal: European Respiratory Journal (2001)

This study has investigated differences in the nocturnal sleep and daytime sleepiness among patients with obstructive sleep apnoea syndrome (OSAS), upper airway resistance (UARS), sleep hypopnoea syndrome, and normal control subjects, using sleep scoring and spectral activity analysis of the electroencephalogram (EEG). Twelve nonobese males with UARS aged 30–60 yrs were recruited. These subjects were strictly matched for age and body mass index with twelve OSAS patients, 12 sleep hypopnoea syndrome patients, and 12 normal controls, all male. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS) and the Multiple Sleep Latency Test (MSLT). The macrostructure of sleep was determined using international criteria and spectral analysis of the sleep EEG was obtained from a central lead. The sleep macrostructure of OSAS and UARS patients was significantly different from that of controls. These patients were also sleepier during the daytime than controls. Complaints of tiredness and daytime sleepiness, ESS and MSLT scores were similar in the different patient groups. Mild dysmorphia was present in all three patient groups. However, nocturnal sleep was significantly different among the different groups. OSAS patients had significantly more awake time during sleep than the UARS patients. The spectral activity of the total sleep time of the patient groups also differed significantly from that of controls. When the sleep spectral activity of UARS and OSAS patients were compared, OSAS patients had less slow wave sleep activity than UARS patients. UARS patients had a significantly higher absolute power in the 7–9 Hz bandwidth than OSAS patients. The absolute delta power over the different sleep cycles was also different between controls and patients, and between UARS and OSAS patients. There are clear differences in the macrostructure and spectral activity of sleep between upper airway resistance and obstructive sleep apnoea syndrome patients, demonstrated by differences in the cortical activity recorded in the central lead during sleep. Despite these nocturnal sleep differences, the tests of subjective daytime sleepiness are not significantly different.
Interaction of Baroreceptor and Chemoreceptor Reflexes MODULATION OF THE CHEMORECEPTOR REFLEX BY CHANGES IN BARORECEPTOR ACTIVITY
Authors: Donald D. Heistad, Francois M. Abboud, Allyn L. Mark, Phillip G. Schmid
Journal: Journal of Clinical Investigation (1974)

The purpose of this study was to determine whether the level of arterial pressure and degree of baroreceptor activation affect responses to stimulation of chemoreceptors. Chemoreceptors were stimulated by injecting nicotine into the common carotid artery of anesthetized and paralyzed dogs. Responses were observed in the innervated gracilis muscle, perfused at constant flow while perfusion pressure was measured. Arterial pressure was lowered by bleeding the animals and raised by transient occlusion of the descending aorta. Vasoconstrictor responses to stimulation of chemoreceptors were enhanced by hypotension and inhibited by elevation of arterial pressure. Potentiation of the chemoreceptor reflex by hemorrhagic hypotension was not the result of altered vascular resistance in the gracilis muscle, sensitization of chemoreceptors by catecholamines or acidosis, or changes in cerebral perfusion pressure. Additional studies were done in which we excluded the possibility that the changes resulted from direct effects of changes in arterial pressure on chemoreceptors. Both carotid bifurcations were isolated and perfused. On one side, pressure was raised to stimulate the carotid sinus baroreceptors. On the other side, the carotid body chemoreceptors were stimulated by nicotine or by hypoxic and hypercapnic blood. Activation of baroreceptors on one side attenuated the vasoconstrictor response to chemoreceptor stimulation on the other side. This excludes a direct effect of changes in arterial pressure on the chemoreceptors and suggests a central interaction of these reflexes. We conclude that vasoconstrictor responses to stimulation of chemoreceptors are potentiated by hypotension and inhibited by transient hypertension. These effects appear to result at least in part from a central interaction of chemoreceptor and baroreceptor reflexes.
A monoclonal antibody to sialophorin (CD43) induces homotypic adhesion and activation of human monocytes.
Authors: Y H Nong, E Remold-O'Donnell, T W LeBien, H G Remold
Journal: The Journal of Experimental Medicine (1989)

Treatment of human monocytes for 24-48 h with the anti-CD43 mAb L10 caused five- to sevenfold stimulation of hydrogen peroxide-producing capacity, an established characteristic of activated monocytes. Peroxide-producing capacity induced by L10 antibody (1.6 +/- 0.3 nmol H2O2/micrograms DNA/h) was comparable with that induced by IFN-gamma (1.3 +/- 0.4 nmol H2O2/micrograms DNA/h), but appeared more rapidly (maximal at 24 h) than in the IFN-gamma-treated monocytes (maximal at 48 h). Treatment of monocytes with L10 mAb also caused dramatic increase in aggregation (homotypic adhesion). Induction of monocyte aggregation by L10 mAb required incubation for 1-8 h in the presence of Mg2+ and was abrogated by TA-1, an anti-LFA-1-alpha mAb. Thus, L10-induced monocyte activation proceeds via a Mg2+-requiring aggregation stage involving LFA-1. Whereas the extent of monocyte aggregation induced by L10 mAb and by IFN-gamma were comparable, the L10-induced aggregation occurred more rapidly (maximal at 8 h) than the IFN-gamma-induced aggregation (maximal at 24 h). The more rapid appearance of aggregation and increased hydrogen peroxide capacity in L10-treated monocytes suggests that the L10-induced activation pathway is independent of IFN-gamma-and IFN-gamma-R dependent events. These findings suggest that the surface molecule CD43 is the receptor of an independent activation pathway that leads in lymphocytes to proliferation and in monocytes to activation.
Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged ≥70 years with advanced ovarian cancer—a study by the AGO OVAR Germany
Authors: F. Hilpert, A. du Bois, E.R. Greimel, J. Hedderich, G. Krause, L. Venhoff, S. Loibl, J. Pfisterer
Journal: Annals of Oncology (2006)
Detection and HER2 Expression of Circulating Tumor Cells: Prospective Monitoring in Breast Cancer Patients Treated in the Neoadjuvant GeparQuattro Trial
Authors: Sabine Riethdorf, Volkmar Müller, Liling Zhang, Thomas Rau, Sibylle Loibl, Martina Komor, Marc Roller, Jens Huober, Tanja Fehm, Iris Schrader, Jörn Hilfrich, Frank Holms, Hans Tesch, Holger Eidtmann, Michael Untch, Gunter von Minckwitz, Klaus Pantel
Journal: Clinical Cancer Research (2010)

This study was aimed at detecting and characterizing circulating tumor cells (CTC) before and after neoadjuvant therapy (NT) in the peripheral blood of patients with breast cancer.The clinical trial GeparQuattro incorporated NT approaches (epirubicin/cyclophosphamide prior to randomization to docetaxel alone, docetaxel in combination with capecitabine, or docetaxel followed by capecitabine) and additional trastuzumab treatment for patients with HER2-positive tumors. We used the Food and Drug Administration-approved CellSearch system for CTC detection and evaluation of HER2 expression and developed HER2 immunoscoring for CTC.We detected > or =1 CTC/7.5 mL in 46 of 213 patients (21.6%) before NT and in 22 of 207 patients (10.6%) after NT (P = 0.002). Twenty (15.0%) initially CTC-positive cases were CTC-negative after NT, whereas 11 (8.3%) cases were CTC-positive after NT, although no CTC could be found before NT. CTC detection did not correlate with primary tumor characteristics. Furthermore, there was no association between tumor response to NT and CTC detection. HER2-overexpressing CTC were observed in 14 of 58 CTC-positive patients (24.1%), including 8 patients with HER2-negative primary tumors and 3 patients after trastuzumab treatment. CTC scored HER2-negative or weakly HER2-positive before or after NT were present in 11 of 21 patients with HER2-positive primary tumors. HER2 overexpression on CTC was restricted to ductal carcinomas and associated with high tumor stage (P = 0.002).CTC number was low in patients with primary breast cancer. The decrease in CTC incidence during treatment was not correlated with standard clinical characteristics and primary tumor response. Information on the HER2 status of CTC might be helpful for stratification and monitoring of HER2-directed therapies.
The family and disease management in Hispanic and European-American patients with type 2 diabetes.
Authors: L Fisher, C A Chesla, M M Skaff, C Gilliss, J T Mullan, R J Bartz, R A Kanter, C P Lutz
Journal: Diabetes Care (2000)

To determine the relationship between the characteristics of families involved in disease management and the self-care practices of Hispanic and European-American (EA) patients with type 2 diabetes.A total of 74 Hispanic patients and 113 EA patients with type 2 diabetes recruited from managed care settings were assessed on three domains of family life (family structure/organization, family world view, and family emotion management [four scales]) and five areas of disease management (biological, general health and function status, emotional tone, quality of life, and behavioral [seven scales]). Analyses assessed the independent associations of patient sex, family, and sex by family interactions with disease management.Both sex and the three domains of family life were related to disease management, but the results varied by ethnic group. For EA patients, sex, family world view, and family emotion management were related to disease management (scores for Family Coherence were negatively associated with HbA1c level and depression, and poor scores for Conflict Resolution were linked with high depression); for Hispanic patients, sex and family structure/organization were related to disease management (high scores for Organized Cohesiveness were associated with good diet and exercise, and high scores for Family Sex-Role Traditionalism were related to high quality of life). No significant interactions with sex occurred.Characteristics of the family setting in which disease management takes place are significantly linked to patient self-care behavior, and these linkages vary by patient ethnicity. A family's multiple independent dimensions provide multiple targets for intervention, and differences in family norms, structures, and emotion management should be considered to ensure that interventions are compatible with the setting of disease management.
Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry.
Authors: Y Fujimura, R Kamoi, M Iida
Journal: Gut (1996)

BACKGROUND--The mechanism of ulceration in Crohn9s disease remains unknown. AIMS--To clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn9s disease. METHODS--After identification of colonic lymphoid nodules and aphthoid lesions by magnifying colonoscopy, 76 biopsy specimens were obtained from 10 patients with Crohn9s disease and three patients with colonic lymphoid hyperplasia. This study correlated magnifying colonoscopic, electron microscopic, and immunohistochemical findings of biopsy specimens. RESULTS--In Crohn9s disease, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy, showed surface erosions 150-200 microns in size. These lymphoid nodules with red halos had small erosions either light microscopically or electron microscopically in 18 of 21 specimens (86%). Correlation of scanning and transmission electron microscopy showed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was limited in M cells of FAE in the patients with lymphoid hyperplasia without inflammatory bowel disease. In Crohn9s disease patients in remission, however, HLA-DR antigen was strongly expressed over the entire FAE of lymphoid nodules with a red halo endoscopically, while the expression was weak and irregular in the mucosa surrounding the lymphoid nodules. HLA-DR was strongly expressed in the entire inflamed colonic mucosa in the active stage. CONCLUSION--The red halo appearance surrounding lymphoid follicles seems to precede visible aphthoid ulcers and suggests that ulcerations in Crohn9s disease originate from FAE, possibly related to its physiological role as a portal of entry for potentially pathogenic agents.