tbuckley/cabot-search huggingface dataset:
New catheter technique for recording left free-wall accessory atrioventricular pathway activation. Identification of pathway fiber orientation.
Authors: W M Jackman, K J Friday, J A Yeung-Lai-Wah, D M Fitzgerald, B Beck, A J Bowman, P Stelzer, L Harrison, R Lazzara
Journal: Circulation (1988)

The ability to record accessory atrioventricular (AV) pathway activation consistently may be uniquely beneficial in improving pathway localization, identifying anatomic relations, and providing insight into unusual conduction properties. For the purpose of recording left AV accessory pathway activation, an electrode catheter was specially designed for use in the coronary sinus. The orthogonal catheter has three sets of four electrodes spaced evenly around the circumference. Electrograms were recorded at low gain (less than 1 cm/mV) between adjacent electrodes on the same set (interelectrode distance, 1.5 mm, center to center). This provides a recording dipole perpendicular to the atrioventricular groove to enhance recording of accessory pathway activation while minimizing overlapping atrial or ventricular potentials. The orthogonal electrode catheter was used in the electrophysiological study of 48 consecutive patients with 59 left AV accessory pathways. The catheter could be advanced along the coronary sinus beyond the site of earliest retrograde atrial activation in 49 of the 59 accessory pathways. Activation potentials were recorded from 45 of the 49 (92%) accessory pathways accessible to the catheter (5 of 5 anterior, 8 of 8 anterolateral, 15 of 16 lateral, 5 of 5 posterolateral, 5 of 5 posterior, and 7 of 10 posteroseptal). Accessory pathway potentials were validated by dissociating them from both atrial and ventricular activation by programmed-stimulation techniques. During surgery, accessory pathway potentials were identified from orthogonal catheter electrodes in the coronary sinus in 14 of 16 accessory pathways (12 patients). Epicardial mapping confirmed the location of the accessory pathway, and direct pressure over the orthogonal catheter electrode that recorded the accessory pathway potential resulted in transient conduction block in nine of the 14 accessory pathways. Orthogonal electrode maps of the coronary sinus identified an oblique course in 39 of 45 recorded accessory pathways. Thirty-two of 38 left free-wall accessory pathways were oriented with atrial insertion 4-30 mm (median, 14 mm) proximal (posterior) to the ventricular insertion. In the remaining six free-wall accessory pathways, the lateral excursion could not be determined because either only the atrial end of the accessory pathway was recorded or activation of multiple pathway fibers prevented tracking of individual strands. The seven recorded posteroseptal pathways exhibited accessory pathway potentials throughout an 8-18-mm (median, 10 mm) length of the proximal coronary sinus, but fiber orientation was difficult to determine.(ABSTRACT TRUNCATED AT 400 WORDS)
Overproduction of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis–like lesions
Authors: Christian Vestergaard, Hiroyuki Yoneyama, Masako Murai, Kohichiro Nakamura, Kunihiko Tamaki, Yuya Terashima, Toshio Imai, Osamu Yoshie, Tatsuro Irimura, Hitoshi Mizutani, Kouji Matsushima
Journal: Journal of Clinical Investigation (1999)

We have examined the expression of chemokines and their receptors in the atopic dermatitis–like (AD-like) lesions of NC/Nga mice. Such lesions develop when the mice are kept in conventional conditions, but not when they are kept isolated from specific pathogens. The thymus- and activation-regulated chemokine TARC is unexpectedly highly expressed in the basal epidermis of 14-week-old mice with lesions, whereas it is not expressed in the skin without lesions. Production of TARC by keratinocytes was confirmed by culturing murine keratinocytic cell line cells (PAM212) with TNF-α, IFN-γ, or IL-1β. Expression of another Th2 chemokine, macrophage-derived chemokine (MDC), was observed in the skin from mice kept in both conventional and pathogen-free conditions, but expression of MDC was increased severalfold in the skin with lesions. The cellular origin of MDC was identified to be dermal dendritic cells. Infiltration of the skin by IL-4–producing T cells and mast cells, and the increase of CCR4 mRNA in the skin, coincided with the development of AD lesions. These observations indicate that TARC and MDC actively participate in the pathogenesis of AD-like lesions in NC/Nga mice and that these Th2 chemokines could be novel targets for intervention therapy of AD in humans.
Clinical and Biomarker Outcomes of the Phase II Vandetanib Study from the BATTLE Trial
Authors: Anne S. Tsao, Suyu Liu, J. Jack Lee, Christine M. Alden, George R. Blumenschein, Roy Herbst, Suzanne E. Davis, Edward Kim, Scott Lippman, John Heymach, Hai Tran, XiMing Tang, Ignacio Wistuba, Waun Ki Hong
Journal: Journal of Thoracic Oncology (2013)
A comparison of safety profiles of tumour necrosis factor α inhibitors and rituximab therapy in patients with rheumatoid arthritis and chronic hepatitis C
Authors: Yi-Ming Chen, Hsin-Hua Chen, Yi-Hsing Chen, Tsu-Yi Hsieh, Chia-Wei Hsieh, Wei-Ting Hung, Joung-Liang Lan, Der-Yuan Chen
Journal: Annals of the Rheumatic Diseases (2014)

Hepatitis C virus (HCV) infection is prevalent worldwide and is associated with cirrhosis and hepatocellular carcinoma. Although antitumour necrosis factor (anti-TNF) α agents may affect the competence of the immune system against viral infection,1 some studies have demonstrated that TNF-α inhibitors may be safe in patients with chronic HCV infection.2 ,3 A recent randomised clinical trial showed that rheumatoid arthritis (RA) patients with chronic HCV were treated successfully with etanercept without elevation of transaminases and HCV viral load.4 However, rituximab (RTX) is associated with increasing HCV RNA levels in lymphoma patients undergoing RTX combined with chemotherapy.5 ,6 RTX-related HCV reactivation was also observed in RA patients.7 Therefore, biological therapies of different mechanism of action may influence on HCV replication differently. To test this hypothesis, we conducted a retrospective safety profile review of RA patients with concomitant HCV infection treated …
Inhibition of Pancreatic Glucagon Responses to Arginine by Human Insulin (recombinant DNA) and Purified Porcine Insulin in Normal and Diabetic Subjects
Authors: Sotos Raptis, Dimitrios Hadjidakis, Franz Enzmann, Athanassios Raptis, Emmanuel Diamantopoulos, Julian Rosenthal
Journal: Diabetes Care (1982)

This study investigates and compares human insulin (recombinant DNA) and purified porcine insulin (PPI) in healthy volunteers and in type II diabetic patients, in terms of whether both these insulins were capable of influencing in a different manner pancreatic glucagon, C-peptide, and free fatty acids (FFA) concentrations. The findings reveal that the β-cell of human pancreas apparently recognizes human insulin more readily than PPI, as assessed by the inhibition of C-peptide, and a similar conclusion follows for the α-cell; this conclusion is underscored by the inhibited glucagon values. The delayed increments of glucagon under human insulin following arginine stimulation may be the result of a more rapid insulin absorption from subcutaneous tissue and a greater biologic action of this insulin in comparison with the PPI. Finally, human insulin has additional properties as demonstrated by its stronger antilipolytic effects.
Characterization of the protective capacity and immunogenicity of the 69-kD outer membrane protein of Bordetella pertussis.
Authors: R D Shahin, M J Brennan, Z M Li, B D Meade, C R Manclark
Journal: The Journal of Experimental Medicine (1990)

Immunization with the 69-kD outer membrane protein (OMP) of Bordetella pertussis protected neonatal mice against lethal respiratory challenge with B. pertussis 18323. Active immunization elicited a serum IgG anti-69-kD OMP response at the time of challenge, with IgG anti-69-kD OMP antibodies detected in bronchoalveolar lavage fluid after challenge. Intravenous administration of BPE8, a monoclonal IgG1 anti-69-kD OMP, also protected young mice against B. pertussis challenge. Intravenously injected BPE8 was detected in the lungs of mice at the time of aerosol challenge, suggesting that the presence of specific antibody in the lungs may mediate protection. Thus the 69-kD OMP of B. pertussis is a protective antigen in mice that elicits specific serum antibody that can transude to the lung. The 69-kD OMP was detected in a preparation of a Takeda acellular vaccine by immunoblot analysis and a serum antibody response to the 69-kD OMP was observed in 18-mo-old children boosted with this preparation of Japanese acellular vaccine. Our results demonstrate that the B. pertussis 69-kD OMP is a protective antigen in animals, is immunogenic in humans, and is present in a preparation of acellular pertussis vaccine that is widely used in Japan. These findings indicate that the 69-kD OMP should be seriously considered as a candidate for inclusion in new formulations of antigenically defined acellular pertussis vaccines.
Environmental Factors and Type 1 Diabetes
Authors: Gisela Dahlquist
Journal: Diabetes Care (2001)

In the July 2000 issue of Diabetes Care , Hummel et al. (1) reported a 2-year follow-up of the German BABYDIAB Study. Indeed, the BABYDIAB Study is an interesting and comparably large prospective study that follows infants of mothers or fathers with type 1 diabetes. So far, 10 children have developed diabetes and an additional 21 have developed islet cell antibodies. In the present article, Hummel et al. (2) attempted to study the possible effects of environmental risk factors, such as breast-feeding and vaccination, as well as measles, mumps, and rubella infections, to determine the likelihood of genetically susceptible children to develop diabetes or β-cell autoimmunity, as mirrored by islet autoantibodies. The authors found no significant effect of breast-feeding prevalence, duration of vaccinations, or reported childhood viral infections, and they concluded that these environmental factors are unlikely to have a major causal influence on initiating islet autoimmunity in genetically susceptible children. Nevertheless, it is important to identify what is meant by …
CD8+ T Cell–Mediated Skin Disease in Mice Lacking IRF-2, the Transcriptional Attenuator of Interferon-α/β Signaling
Authors: Shigeaki Hida, Kouetsu Ogasawara, Kojiro Sato, Masaaki Abe, Hiroshi Takayanagi, Taeko Yokochi, Takeo Sato, Sachiko Hirose, Toshikazu Shirai, Shinsuke Taki, Tadatsugu Taniguchi
Journal: Immunity (2000)
Global Histone Modifications in Breast Cancer Correlate with Tumor Phenotypes, Prognostic Factors, and Patient Outcome
Authors: Somaia E. Elsheikh, Andrew R. Green, Emad A. Rakha, Des G. Powe, Rabab A. Ahmed, Hilary M. Collins, Daniele Soria, Jonathan M. Garibaldi, Claire E. Paish, Amr A. Ammar, Matthew J. Grainge, Graham R. Ball, Magdy K. Abdelghany, Luisa Martinez-Pomares, David M. Heery, Ian O. Ellis
Journal: Cancer Research (2009)

Post-translational histone modifications are known to be altered in cancer cells, and loss of selected histone acetylation and methylation marks has recently been shown to predict patient outcome in human carcinoma. Immunohistochemistry was used to detect a series of histone lysine acetylation (H3K9ac, H3K18ac, H4K12ac, and H4K16ac), lysine methylation (H3K4me2 and H4K20me3), and arginine methylation (H4R3me2) marks in a well-characterized series of human breast carcinomas (n = 880). Tissue staining intensities were assessed using blinded semiquantitative scoring. Validation studies were done using immunofluorescence staining and Western blotting. Our analyses revealed low or absent H4K16ac in the majority of breast cancer cases (78.9%), suggesting that this alteration may represent an early sign of breast cancer. There was a highly significant correlation between histone modifications status, tumor biomarker phenotype, and clinical outcome, where high relative levels of global histone acetylation and methylation were associated with a favorable prognosis and detected almost exclusively in luminal-like breast tumors (93%). Moderate to low levels of lysine acetylation (H3K9ac, H3K18ac, and H4K12ac), lysine (H3K4me2 and H4K20me3), and arginine methylation (H4R3me2) were observed in carcinomas of poorer prognostic subtypes, including basal carcinomas and HER-2-positive tumors. Clustering analysis identified three groups of histone displaying distinct pattern in breast cancer, which have distinct relationships to known prognostic factors and clinical outcome. This study identifies the presence of variations in global levels of histone marks in different grades, morphologic types, and phenotype classes of invasive breast cancer and shows that these differences have clinical significance.
Coronary vasospasm and sumatriptan: Authors' reply
Authors: M. Armitage, N. Curzen, F. Willett
Journal: BMJ (1992)

metal's angina are both given as contraindications in the datasheet for sumatriptan; the datasheet also includes advice against the concomitant use of ergotamine.Willett and colleagues' report there- fore clearly highlights the need for these warnings and emphasises that sumatriptan should be avoided if there is a history of ischaemic heart disease or undiagnosed chest pain.
O32 PROSPECTIVE EVALUATION OF THE CORRELATION BETWEEN HEMOSTATIC ALTERATIONS AND INCIDENCE OF PORTAL VEIN THROMBOSIS IN PATIENTS WITH LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA
Authors: A. Zanetto, A. Ferrarese, A. Vitale, U. Cillo, K.-I. Rodriguez, M. Fadin, S. Gavasso, C. Radu, P. Zerbinati, P. Simioni, F. Farinati, G. Germani, F.P. Russo, P. Burra, M. Senzolo
Journal: Journal of Hepatology (2014)
H <sub>2</sub> O <sub>2</sub> Is the Transferrable Factor Mediating Flow-Induced Dilation in Human Coronary Arterioles
Authors: Yanping Liu, Aaron H. Bubolz, Suelhem Mendoza, David X. Zhang, David D. Gutterman
Journal: Circulation Research (2011)

Endothelial derived hydrogen peroxide (H(2)O(2)) is a necessary component of the pathway regulating flow-mediated dilation (FMD) in human coronary arterioles (HCAs). However, H(2)O(2) has never been shown to be the endothelium-dependent transferrable hyperpolarization factor (EDHF) in response to shear stress.We examined the hypothesis that H(2)O(2) serves as the EDHF in HCAs to shear stress.Two HCAs were cannulated in series (a donor intact vessel upstream and endothelium-denuded detector vessel downstream). Diameter changes to flow were examined in the absence and presence of polyethylene glycol catalase (PEG-CAT). The open state probability of large conductance Ca(2+)-activated K(+) (BK(Ca)) channels in smooth muscle cells downstream from the perfusate from an endothelium-intact arteriole was examined by patch clamping. In some experiments, a cyanogen bromide-activated resin column bound with CAT was used to remove H(2)O(2) from the donor vessel. When flow proceeds from donor to detector, both vessels dilate (donor:68±7%; detector: 45±11%). With flow in the opposite direction, only the donor vessel dilates. PEG-CAT contacting only the detector vessel blocked FMD in that vessel (6±4%) but not in donor vessel (61±13%). Paxilline inhibited dilation of endothelium-denuded HCAs to H(2)O(2). Effluent from donor vessels elicited K(+) channel opening in an iberiotoxin- or PEG-CAT-sensitive fashion in cell-attached patches but had little effect on channel opening on inside-out patches. Vasodilation of detector vessels was diminished when exposed to effluent from CAT-column.Flow induced endothelial production of H(2)O(2), which acts as the transferrable EDHF activating BK(Ca) channels on the smooth muscle cells.
Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review
Authors: E.B. Janssen, A.C.M. Rijkers, K. Hoppenbrouwers, C. Meuleman, T.M. D'Hooghe
Journal: Human Reproduction Update (2013)

Endometriosis associated with pain symptoms in adolescents has been extensively reported, but the exact prevalence is unclear because pain symptoms may be atypical and endometriosis can only be diagnosed by laparoscopy. The aim of this paper is to provide a systematic review of the prevalence of endometriosis diagnosed by laparoscopy in adolescents. A systematic literature search was carried out for relevant articles published between 1980 and 2011 in the databases PUBMED and EMBASE, based on the keywords ‘endometriosis’, ‘laparoscopy’, ‘adolescents’ and ‘chronic pelvic pain (CPP)’. In addition, the reference lists of the selected articles were examined. Based on 15 selected studies, the overall prevalence of visually confirmed endometriosis was 62% (543/880; range 25–100%) in all adolescent girls undergoing laparoscopic investigation, 75% (237/314) in girls with CPP resistant to treatment, 70% (102/146) in girls with dysmenorrhea and 49% (204/420) in girls with CPP that is not necessarily resistant to treatment. Among the adolescent girls with endometriosis, the overall prevalence of American Society of Reproductive Medicine classified moderate–severe endometriosis was 32% (82/259) in all girls, 16% (17/108) in girls with CPP resistant to treatment, 29% (21/74) in girls with dysmenorrhea and 57% (44/77) in girls with CPP that is not necessarily resistant to treatment. Due to the quality of the included papers an overestimation of the prevalence and/or severity of endometriosis is possible. About two-thirds of adolescent girls with CPP or dysmenorrhea have laparoscopic evidence of endometriosis. About one-third of these adolescents with endometriosis have moderate–severe disease. The value of early detection of endometriosis in symptomatic adolescents and the indications for laparoscopic investigation in adolescents require more research.
Reinvigorating exhausted HIV-specific T cells via PD-1–PD-1 ligand blockade
Authors: Gordon J. Freeman, E. John Wherry, Rafi Ahmed, Arlene H. Sharpe
Journal: The Journal of Experimental Medicine (2006)

The programmed death (PD)-1–PD-1 ligand (PD-L) pathway, which is part of the B7–CD28 family, consists of the PD-1 receptor and its two ligands PD-L1 and PD-L2. Engagement of PD-1 by its ligands inhibits immune responses, and recent work has shown that PD-1 is highly expressed on exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Blockade of this pathway reinvigorates the exhausted T cells, allowing them to expand and produce effector cytokines, raising the issue of whether this pathway has been exploited by a variety of viruses during chronic infection. New studies now extend these observations to HIV infection and human disease.
Contractile and morphological impairment of cultured fetal mouse myocytes induced by oxygen radicals and oxidants. Correlation with intracellular Ca2+ concentration.
Authors: T Y Nakamura, K Goda, T Okamoto, T Kishi, T Nakamura, K Goshima
Journal: Circulation Research (1993)

There is evidence that reperfusion injury of cardiac tissue may be caused by the generation of oxygen-derived free radicals and oxidants and by the induction of intracellular calcium overload, although the relation between these two mechanisms of injury is uncertain. In addition, the relation between the types of cellular injury and specific active species is unclear. In an attempt to resolve these problems, we investigated the effects of oxygen radicals and oxidants, which are purportedly generated during reperfusion after prolonged ischemia, and various antioxidants on contractility and morphology of cultured fetal mouse cardiac myocytes. Xanthine oxidase in the presence of xanthine, H2O2, HOCl, and NH2Cl induced cessation of spontaneous beating followed by cessation of electrical stimulation-elicited beating but did not induce an increase in [Ca2+]i. After prolonged incubation with xanthine oxidase + xanthine and H2O2, the cardiac myocytes showed morphological degeneration (at least 80% of the cells developed hypercontraction) with a concomitant increase in [Ca2+]i. These observations suggest that contractile impairment does not result in an increase of [Ca2+]i, but hypercontraction does. Catalase, but not superoxide dismutase, protected the cultured cardiac myocytes against xanthine oxidase + xanthine- and H2O2-induced contractile and morphological impairment. In the light of this observation, we hypothesize that the superoxide anion is not responsible for these types of impairment. Addition of dimethylthiourea (an .OH scavenger) and intracellular preloading with deferoxamine (an iron chelator) protected the myocytes against H2O2-induced contractile and morphological damage, but intracellular preloading with iron enhanced it. These observations led us to hypothesize that intracellularly generated .OH may be a mediator of H2O2-induced injury to cultured cardiac myocytes. In addition, we observed that H2O2 itself induced cessation of spontaneous but not electrical stimulation-elicited beating.
Tunable Plasmonic Nanoprobes for Theranostics of Prostate Cancer
Authors: Ekaterina Y. Lukianova-Hleb, Alexander O. Oginsky, Adam P. Samaniego, Derek L. Shenefelt, Daniel S. Wagner, Jason H. Hafner, Mary C. Farach-Carson, Dmitri O. Lapotko
Journal: Theranostics (2011)

Theranostic applications require coupling of diagnosis and therapy, a high degree of specificity and adaptability to delivery methods compatible with clinical practice.The tunable physical and biological effects of selective targeting and activation of plasmonic nanobubbles (PNB) were studied in a heterogeneous biological microenvironment of prostate cancer and stromal cells.All cells were targeted with conjugates of gold nanoparticles (NPs) through an antibody-receptor-endocytosis-nanocluster mechanism that produced NP clusters.The simultaneous pulsed optical activation of intracellular NP clusters at several wavelengths resulted in higher optical contrast and therapeutic selectivity of PNBs compared with those of gold NPs alone.The developed mechanism was termed "rainbow plasmonic nanobubbles."The cellular effect of rainbow PNBs was tuned in situ in target cells, thus supporting a theranostic algorithm of prostate cancer cell detection and follow-up guided destruction without damage to collateral cells.The specificity and tunability of PNBs is promising for theranostic applications and we discuss a fiber optic platform that will capitalize on these features to bring theranostic tools to the clinic.
Chromatin Immunoprecipitation–on-Chip Reveals Stress-Dependent p53 Occupancy in Primary Normal Cells but Not in Established Cell Lines
Authors: Helena Shaked, Idit Shiff, Miriam Kott-Gutkowski, Zahava Siegfried, Ygal Haupt, Itamar Simon
Journal: Cancer Research (2008)

Abstract The p53 tumor suppressor protein is a transcription factor that plays a key role in the cellular response to stress and cancer prevention. Upon activation, p53 regulates a large variety of genes causing cell cycle arrest, apoptosis, or senescence. We have developed a p53-focused array, which allows us to investigate, simultaneously, p53 interactions with most of its known target sequences using the chromatin immunoprecipitation (ChIP)-on-chip methodology. Applying this technique to multiple cell types under various growth conditions revealed a profound difference in p53 activity between primary cells and established cell lines. We found that, in peripheral blood mononuclear cells, p53 exists in a form that binds only a small subset of its target regions. Upon exposure to genotoxic stress, the extent of targets bound by p53 significantly increased. By contrast, in established cell lines, p53 binds to essentially all of its targets irrespective of stress and cellular fate (apoptosis or arrest). Analysis of gene expression in these established lines revealed little correlation between DNA binding and the induction of gene expression. Our results suggest that nonactivated p53 has limited binding activity, whereas upon activation it binds to essentially all its targets. Additional triggers are most likely required to activate the transcriptional program of p53. [Cancer Res 2008;68(23):9671–7]