tbuckley/cabot-search huggingface dataset:
Selective cleavage of nuclear autoantigens during CD95 (Fas/APO-1)-mediated T cell apoptosis.
Authors: C A Casiano, S J Martin, D R Green, E M Tan
Journal: The Journal of Experimental Medicine (1996)

Intracellular proteases appear to be important mediators of apoptosis. Substrates cleaved by proteases during apoptosis include nuclear autoantigens targeted in systemic autoimmune diseases. Using human autoantibodies as probes, we demonstrate here that T cell apoptosis mediated by CD95 (Fas/APO-1) is associated with substantial cleavage of a subset of nuclear autoantigens (7 of 33 examined). This subset included poly (ADP-ribose) polymerase, the 70-kD protein of the U1 small nuclear ribonucleoprotein particle, lamin B, the nuclear mitotic apparatus protein NuMA, DNA topoisomerases I and II, and the RNA polymerase I upstream binding factor UBF. Several of the cleaved autoantigens are involved in ensuring the integrity and proper conformation of DNA in the nucleus through interactions with the nuclear matrix, suggesting the possibility that their cleavage may contribute to the collapse of nuclear structure during apoptosis. The relative cleavage kinetics indicated that the autoantigens were targeted at various times after induction of apoptosis, suggesting either differential accessibility or activation of distinct proteases during the cell death process. These data reinforce the hypothesis that apoptosis is accompanied by selective cleavage of key substrates and not by a generalized degradation of intracellular material.
The chromosomal analysis of human oocytes. An overview of established procedures
Authors: F. Pellestor, T. Anahory, S. Hamamah
Journal: Human Reproduction Update (2004)

The cytogenetic survey of mature human oocytes has been and remains a subject of great interest because of the prevalence of aneuploidy of maternal origin in abnormal human conceptuses, and the lack of understanding about the non-disjunction processes in human meiosis. The first attempts to analyse the chromosomal content of human female gametes were made in the early 1970s, and led to limited data because of the paucity of materials and the inadequacy of the procedure used. The years to follow brought a resurgence of interest in this field, because of the development of human IVF techniques which made oocytes unfertilized in vitro available for cytogenetic analysis. Numerous studies have since been performed. However, the difficulties in obtaining good chromosome preparations and of performing accurate chromosome identification have reduced the viability of these studies, resulting in large variations in the reported incidences of chromosomal abnormalities. The further introduction of new procedures for oocyte fixation and the screening of large oocyte samples have allowed more reliable data to be obtained and to identify premature chromatid separation as a major mechanism in aneuploidy occurrence. The last decade has been privileged to witness the adaptation of molecular cytogenetic techniques to human oocytes, and thus various powerful procedures have been tried not only on female gametes, but also on polar bodies, involving sequential and multicolour fluorescent in situ hybridization (FISH) labelling, comparative genomic hybridization (CGH), spectral karyotyping and alternative methods such as primed in situ labelling (PRINS) and peptide nucleic acid (PNA) techniques. A large body of data has been obtained, but these studies also display a great variability in the frequency of abnormalities, which may be essentially attributable to the technical limitations of these in situ methods when applied to human oocytes. However, molecular cytogenetic approaches have also evidenced the co-existence of both whole chromosome non-disjunction and chromatid separation in maternal aneuploidy. In addition, the extension of these techniques to oocyte polar body materials has provided additional data on the mechanism of meiotic malsegregation. Improvements of some of these techniques have already been reported. The further development of new approaches for the in situ analysis of human meiosis will increase the impact of cytogenetic investigation of human oocytes in the understanding of aneuploidy processes in humans.
Ventricular pressure-volume curve indices change with end-diastolic pressure.
Authors: S A Glantz
Journal: Circulation Research (1976)

Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed indices has been shown convincingly to discriminate one group of patients from another. While this situation in part arises from the relatively large amount of noise introduced by the technical difficulties of measuring synchronous pressures and volumes during diastole in man, ther is a more fundamental difficulty. In practice, one can measure only a short segment of the entire pressure-volume curve, and the values of all diastolic pressure-volume curve parameters investigated change significantly when one uses different segments of the same pressure-volume curve to compute them. These results were derived from relatively noise-free pressure-volume curves obtained by filling nine excised dog left ventricles at a known rate and monitoring pressure-volume curve used to compute the parameter. Merely increasing measurement fidelity will not resolve this problem, because none of these parameters accurately characterizes the entire diastolic pressure-volume curbe from a segment like that which one can reasonably expect to obtain from humans.
Oxygen Sensing by Primary Cardiac Fibroblasts
Authors: Sashwati Roy, Savita Khanna, Alice A. Bickerstaff, Sukanya V. Subramanian, Mustafa Atalay, Michael Bierl, Srikanth Pendyala, Dana Levy, Nidhi Sharma, Mika Venojarvi, Arthur Strauch, Charles G. Orosz, Chandan K. Sen
Journal: Circulation Research (2003)

In mammalian organs under normoxic conditions, O2 concentration ranges from 12% to <0.5%, with O2 approximately 14% in arterial blood and <10% in the myocardium. During mild hypoxia, myocardial O2 drops to approximately 1% to 3% or lower. In response to chronic moderate hypoxia, cells adjust their normoxia set point such that reoxygenation-dependent relative elevation of PO2 results in perceived hyperoxia. We hypothesized that O2, even in marginal relative excess of the PO2 to which cardiac cells are adjusted, results in activation of specific signal transduction pathways that alter the phenotype and function of these cells. To test this hypothesis, cardiac fibroblasts (CFs) isolated from adult murine ventricle were cultured in 10% or 21% O2 (hyperoxia relative to the PO2 to which cells are adjusted in vivo) and were compared with those cultured in 3% O2 (mild hypoxia). Compared with cells cultured in 3% O2, cells that were cultured in 10% or 21% O2 demonstrated remarkable reversible G2/M arrest and a phenotype indicative of differentiation to myofibroblasts. These effects were independent of NADPH oxidase function. CFs exposed to high O2 exhibited higher levels of reactive oxygen species production. The molecular signature response to perceived hyperoxia included (1) induction of p21, cyclin D1, cyclin D2, cyclin G1, Fos-related antigen-2, and transforming growth factor-beta1, (2) lowered telomerase activity, and (3) activation of transforming growth factor-beta1 and p38 mitogen-activated protein kinase. CFs deficient in p21 were resistant to such O2 sensitivity. This study raises the vital broad-based issue of controlling ambient O2 during the culture of primary cells isolated from organs.
Growth differentiation factor 15 (<scp>GDF</scp>‐15) in patients admitted for acute heart failure: results from the <scp>RELAX‐AHF</scp> study
Authors: Gad Cotter, Adriaan A. Voors, Margaret F. Prescott, G. Michael Felker, Gerasimos Filippatos, Barry H. Greenberg, Peter S. Pang, Piotr Ponikowski, Olga Milo, Tsushung A. Hua, Min Qian, Thomas M. Severin, John R. Teerlink, Marco Metra, Beth A. Davison
Journal: European Journal of Heart Failure (2015)
The Bone Morphogenetic Protein Antagonist Noggin Regulates Mammalian Cardiac Morphogenesis
Authors: Murim Choi, Rolf W. Stottmann, Yu-Ping Yang, Erik N. Meyers, John Klingensmith
Journal: Circulation Research (2007)

Bone morphogenetic proteins (BMPs) play many roles in mammalian cardiac development. Here we address the functions of Noggin, a dedicated BMP antagonist, in the developing mouse heart. In early cardiac tissues, the Noggin gene is mainly expressed in the myocardial cells of the outflow tract, atrioventricular canal, and future right ventricle. The major heart phenotypes of Noggin mutant embryos are thicker myocardium and larger endocardial cushions. Both defects result from increased cell number. Cell proliferation is increased and cell cycle exit is decreased in the myocardium. Although we find evidence of increased BMP signal transduction in the myocardium and endocardium, we show that the cardiac defects of Noggin mutants are rescued by halving the gene dosage of Bmp4 . In culture, BMP increases the epithelial-to-mesenchymal transformation (EMT) of endocardial explant cells. Increased EMT likely accounts for the enlarged atrioventricular cushion. In the outflow tract cushion, we observed an increased contribution of cardiac neural crest cells to the mutant cushion mesenchyme, although many cells of the cushion were not derived from neural crest. Thus the enlarged outflow tract cushion of Noggin mutants likely arises by increased contributions both of endocardial cells that have undergone EMT as well as cells that have migrated from the neural crest. These data indicate that antagonism of BMP signaling by Noggin plays a critical role in ensuring proper levels of cell proliferation and EMT during cardiac morphogenesis in the mouse.
High-Yield Isolation of Mouse Mammary Tumor Virus
Authors: Howard E. Bond, William T. Hall
Journal: JNCI Journal of the National Cancer Institute (1969)

Rate-zonal centrifugation in fhe zonal ultracentrifuge with subsequent isopycnic banding in a Ficoll in heavy-water gradient was used on milk from mice with a high incidence of mammary cancer. This method provided a rapid means for isolating large quantities of mammary tumor virus (MTV) in a relatively high state of purity. The physical properties of the virus in these systems were investigated. The isopycnic banding density was 1.156 g/ml, and the corrected sedimentation coefficient (S20,w) was between 900 and 1000 for adequately dispersed B particles. Virions, apparently incompletely dispersed, had a broad range of sedimentation coefficients, most particles sedimenting with an S20,w of about 1400. When examined in the electron microscope, the isolated particles appeared nearly free of extraneous material, and frozen and thawed samples were tumorigenic at a dilution of 10−4. By a recently developed MTV hemagglutination immunoassay, virus preparations were shown to be free of interfering substances and consistently gave high liters.
Influence of Gastrin on Human Astrocytic Tumor Cell Proliferation
Authors: I. Camby, I. Salmon, A. Danguy, J.-L. Pasteels, J. Brotchi, J. Martinez, R. Kiss
Journal: JNCI Journal of the National Cancer Institute (1996)

Gastrin and cholecystokinin (CCK) mediate their effects through at least two types of receptors (CCK receptors A and B). While it has been hypothesized that gastrin, a stimulator of gastric acid secretion, is also a neurotransmitter and a stimulator of cell proliferation in various normal and neoplastic tissues, its effect on astrocytic brain tumors has not been actively investigated.Our goal was to determine the effects of gastrin and gastin and/or CCK antagonists on the proliferation in vitro of astrocytic tumor cells by use of both established cell lines and primary cell cultures of tumor tissue.Ten established astrocytic tumor cell lines, SW1088, SW1783, Hs683, H4, U87, U118, U138, U373, T98G, and A172, were studied. The effects of added gastrin (at 0.01, 0.1, and microM) and the gastrin/CCK antagonists L-365,260, CI-988, L-364,718, and JMV 234 (each at 0.01, 0.1, and 1 microM) on the cellular proliferation rates of the 10 cell lines were indirectly measured by use of the colorimetric tetrazolium assay. The influence of gastrin (at 0.01 microM) on the cellular proliferation of primary cultures from nine freshly explanted astrocytic tumors was assessed by means of tritiated thymidine uptake and autoradiography.At specific concentrations, added gastrin increased the cellular proliferation of three established astrocytic cell lines (A172, Hs683, and SW1088), decreased it in two (U373 and T98G), and was without effect on the remaining five. Gastrin decreased cellular proliferation in one primary astrocytic tumor cell culture, stimulated it in five, and had no apparent effect in the remaining three. L-365,260, a CCK receptor B antagonist used at 0.01 microM, increased cellular proliferation in seven cell lines (A172, H4, Hs683, SW1783, T98G, U118, and U138), decreased it in one (U87), and had no effect in the remaining two. CI-988, another CCK receptor B antagonist used at 0.01 microM, inhibited cellular proliferation in five cell lines (A172, H4, SW1783, U373, and U87), stimulated it in two (T98G and U138), and had no effect in three. The CCK receptor A antagonists L-364,718 and JMV 234, both used at 0.01 microM, affected the cellular proliferation of only three of the 10 cell lines.These results suggest that gastrin (and perhaps CCK that belongs to the same peptide family) may play a role in the growth of a substantial proportion of human astrocytic tumors.
Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial
Authors: Feng-Cai Zhu, Jun Zhang, Xue-Feng Zhang, Cheng Zhou, Zhong-Ze Wang, Shou-Jie Huang, Hua Wang, Chang-Lin Yang, Han-Min Jiang, Jia-Ping Cai, Yi-Jun Wang, Xing Ai, Yue-Mei Hu, Quan Tang, Xin Yao, Qiang Yan, Yang-Ling Xian, Ting Wu, Yi-Min Li, Ji Miao, Mun-Hon Ng, James Wai-Kuo Shih, Ning-Shao Xia
Journal: The Lancet (2010)
Prognosis in pulmonary arterial hypertension
Authors: R. Wensel, S. Gläser, C.F. Opitz, R. Ewert
Journal: European Respiratory Journal (2011)

To the Editors:

We read with interest the article by Humbert et al. 1 on the difference in prognosis in prevalent versus incident cohorts of patients with pulmonary arterial hypertension (PAH). The study highlights a survival bias in the prevalent cohort due to under-representation of more severely ill patients that might have died before inclusion in the registry. Humbert et al. 1 subsequently found a 1-yr and 3-yr survival rate of 89% and 69% for the prevalent cohort and 89% and 55% for the incident cohort of patients with idiopathic, familiar or anorexigen-associated PAH, respectively.

Although we acknowledge that prevalent cohorts have a selection bias, it is surprising that this does not refer to a difference in mortality at 1-yr but only later during follow-up. If selection of the sickest patients would account for better survival one would expect the same phenomenon in the incident cohort. This would lead to …
Hysteroscopic myomectomy: a comprehensive review of surgical techniques
Authors: Attilio Di Spiezio Sardo, Ivan Mazzon, Silvia Bramante, Stefano Bettocchi, Giuseppe Bifulco, Maurizio Guida, Carmine Nappi
Journal: Human Reproduction Update (2007)

Hysteroscopic myomectomy currently represents the standard minimally invasive surgical procedure for treating submucous fibroids, with abnormal uterine bleeding and reproductive issues being the most common indications. While hysteroscopic myomectomy has been shown to be safe and effective in the control of menstrual disorders, its effects on infertility remain unclear. The review provides a comprehensive survey of all hysteroscopic techniques used to treat fibroids found completely within the uterine cavity (G0) and those with intramural development (G1 and G2). MEDLINE and EMBASE searches identified published papers from 1970. The choice of the technique mostly depends on the intramural extension of the fibroid, as well as on personal experience and available equipment. 'Resectoscopic slicing' still represents the 'gold standard' technique for treating fibroids G0, even if several other effective techniques including ablation by neodymium-yttrium-aluminum-garnet laser, morcellation and office myomectomy have been proposed. On the other hand, the present review clearly indicates that there is still no single technique proven to be unequivocally superior for treating fibroids G1 and G2. Most techniques aim at the transformation of an intramural fibroid into a totally intracavitary lesion, thus avoiding a deep cut into the myometrium. At present, the 'cold loop' technique seems to represent the best option as it allows a safe and complete removal of such fibroids in just one surgical procedure, while respecting the surrounding healthy myometrium.
TLR9 Signaling in the Tumor Microenvironment Initiates Cancer Recurrence after Radiotherapy
Authors: Chan Gao, Anna Kozlowska, Sergey Nechaev, Haiqing Li, Qifang Zhang, Dewan M.S. Hossain, Claudia M. Kowolik, Peiguo Chu, Piotr Swiderski, Don J. Diamond, Sumanta K. Pal, Andrew Raubitschek, Marcin Kortylewski
Journal: Cancer Research (2013)

Abstract Cancer radiotherapy may be immunogenic, but it is unclear why its immunogenic effects are rarely sufficient to prevent tumor recurrence. Here, we report a novel Toll-like receptor 9 (TLR9)–dependent mechanism that initiates tumor regrowth after local radiotherapy. Systemic inhibition of TLR9, but not TLR4, delayed tumor recurrence in mouse models of B16 melanoma, MB49 bladder cancer, and CT26 colon cancer after localized high-dose tumor irradiation. Soluble factors in the microenvironment of regressing tumors triggered TLR9 signaling in freshly recruited myeloid cells appearing within four days of radiotherapy. The tumorigenic effects of TLR9 depended on MyD88/NF-κB–mediated upregulation of interleukin (IL)-6 expression, which in turn resulted in downstream activation of Jak/STAT3 signaling in myeloid cells. In comparing global gene expression in wild-type, TLR9-, or STAT3-deficient myeloid cells derived from irradiated tumors, we identified a unique set of TLR9/STAT3–regulated genes involved in tumor-promoting inflammation and revascularization. Blocking STAT3 function by two myeloid-specific genetic strategies corrected TLR9-mediated cancer recurrence after radiotherapy. Our results suggest that combining localized tumor irradiation with myeloid cell–specific inhibition of TLR9/STAT3 signaling may help eliminate radioresistant cancers. Cancer Res; 73(24); 7211–21. ©2013 AACR.
Amiodarone Improves Cardiac Sympathetic Nerve Function to Hold Norepinephrine in the Heart, Prevents Left Ventricular Remodeling, and Improves Cardiac Function in Rat Dilated Cardiomyopathy
Authors: Hitoshi Tachikawa, Makoto Kodama, Kenichi Watanabe, Toshihiro Takahashi, Meilei Ma, Takeshi Kashimura, Masahiro Ito, Satoru Hirono, Yuji Okura, Kiminori Kato, Haruo Hanawa, Yoshifusa Aizawa
Journal: Circulation (2005)

Background— It is unclear how amiodarone therapy exerts its effects on left ventricular remodeling and cardiac sympathetic nerve function in chronic heart failure. We investigated long-term effects of amiodarone on rat dilated cardiomyopathy after healing of cardiac myosin–induced autoimmune myocarditis. Methods and Results— Rats were treated with oral amiodarone or vehicle for 6 weeks. We determined cardiac function, left ventricular remodeling, and cardiac sympathetic nerve function with iodine-125–labeled metaiodobenzylguanidine ([I 125 ]MIBG). Amiodarone treatment improved left ventricular pressure, central venous pressure, and rate of isovolumetric contraction and decreased ventricular weight ( P &lt;0.005). Expression of cytokine mRNA was unchanged; expression of atrial natriuretic peptide, collagen III, and transforming growth factor-β 1 mRNA was decreased in amiodarone-treated rats ( P &lt;0.05). Phenotype of myosin heavy chain was moved toward that of normal rats by amiodarone. Initial myocardial uptake of MIBG decreased by 67% ( P &lt;0.001) and washout rate accelerated by 221% in rats with chronic heart failure compared with normal rats. Whereas amiodarone decreased the initial uptake by 71% in normal rats, amiodarone decelerated the early washout and the late washout and improved the late myocardial distribution of MIBG in rats with chronic heart failure (257% compared with vehicle-treated rats with chronic heart failure; P &lt;0.01). In proportion to MIBG distributions, cardiac tissue catecholamines were increased by amiodarone treatment. Conclusions— Long-term amiodarone treatment prevented left ventricular remodeling and improved cardiac function in rat dilated cardiomyopathy. Long-term amiodarone treatment also restored cardiac sympathetic tone to hold norepinephrine in the heart.
Mitigating Case Mix Factors by Choice of Glycemic Control Performance Measure Threshold
Authors: Kathleen E. Bainbridge, Catherine C. Cowie, Keith F. Rust, Judith E. Fradkin
Journal: Diabetes Care (2008)

OBJECTIVE—Performance measures are tools for assessing quality of care but may be influenced by patient factors. We investigated how currently endorsed performance measures for glycemic control in diabetes may be influenced by case mix composition. We assessed differences in A1C performance measure threshold attainment by case mix factors for A1C &amp;gt;9% and examined how lowering the threshold to A1C &amp;gt;8% or &amp;gt;7% changed these differences. RESEARCH DESIGN AND METHODS—Using data from the 1999–2002 National Health and Nutrition Examination Survey for 843 adults self-reporting diabetes, we computed the mean difference in A1C threshold attainment of &amp;gt;9, &amp;gt;8, and &amp;gt;7% by various case mix factors. The mean difference is the average percentage point difference in threshold attainment for population groups compared with that for the overall population. RESULTS—Diabetes medication was the only factor for which the difference in threshold attainment increased at lower thresholds, with mean differences of 5.7 percentage points at A1C &amp;gt;9% (reference), 10.1 percentage points at A1C &amp;gt;8% (P &amp;lt; 0.05), and 14.1 percentage points at A1C &amp;gt;7% (P &amp;lt; 0.001). CONCLUSIONS—As 87% of U.S. adults have A1C &amp;lt;9%, a performance measure threshold of &amp;gt;9% will not drive major improvements in glycemic control. Lower thresholds do not exacerbate differences in threshold attainment for most factors. Reporting by diabetes medication use may compensate for heterogeneous case mix when a performance measure threshold of A1C &amp;gt;8% or lower is used.