tbuckley/cabot-search huggingface dataset:
Abstract 17538: Nanoparticle-Mediated Targeting of a Mitochondria Division Inhibitor, Mdivi-1, to the Mitochondria Induces Cardioprotection from Ischemia-Reperfusion Injury
Authors: Ayako Ishikita, Tetsuya Matoba, Gentaro Ikeda, Yajing Mao, Kaku Nakano, Kenji Sunagawa, Kensuke Egashira
Journal: Circulation (2014)

Background: Mitochondria (MITO) injury plays a major role in the mechanism of myocardial ischemia-reperfusion (IR) injury. Intravenous administration of an inhibitor of MITO permeability transition pore (mPTP) opening, cyclosporine A, at the time of reperfusion can reduce IR injury in animals and patients with acute myocardial infarction (MI), however; the degrees of cardioprotection induced by cyclosporine A seem to be inadequate. Therefore, a more effective modality for inhibiting MITO injury must be developed for cardioprotection from IR injury in acute MI. Here we tested the hypothesis that nanoparticle-mediated targeting of mitochondrial division inhibitor-1 (mdivi-1) to MITO enhances cardioprotection from IR injury.

Methods and Results: We formulated poly(lactic acid/glycolic acid) (PLGA) nanoparticles containing mdivi-1 (Mdivi1-NP) or FITC (FITC-NP). In neonatal rat cardiomyocytes, mitochondrial-targeting of nanoparticles was noted after the addition of hydrogen peroxide (H2O2) that represents oxidative stress during IR (Fig. A). Treatment with Mdivi1-NP (containing 5 μM mdivi-1) markedly attenuated H2O2-induced MITO-division and cardiomyocyte death (Fig. B). In Langendorff perfused mouse heart, treatment with Mdivi1-NP (5 and 50 μM) at the time of reperfusion enhanced the cardioprotection against IR injury achieved by mdivi1 alone (Fig. C). In an in vivo murine model of IR, treatment with Mdivi1-NP (1.2 mg/kg) at the time of reperfusion also enhanced the cardioprotection against IR injury achieved by mdivi1 alone. Interestingly, treatment with Mdivi1-NP reduced IR injury and MITO swelling in mice lacking cyclophilin D (a key regulatory molecule for mPTP opening) (Fig. D).

Conclusions: Nanoparticle-mediated targeting of mdivi1 to the mitochondria enhanced cardioprotection against IR injury through mechanisms independent of mPTP opening. Mdivi1-NP can be developed as a new cardioprotective strategy in acute MI.

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Novel Biomarkers to Discriminate Between Primary Lung Squamous Cell Carcinoma and Adenocarcinoma Identified By the Cap Analysis of Gene Expression (Cage) Method
Authors: K. Takamochi, H. Omiya, Y. Yamanaka, M. Ito, H. Kawaji, S. Oh, Y. Hayashizaki, K. Suzuki
Journal: Annals of Oncology (2014)
Breast Cancer Cell Targeting by Prenylation Inhibitors Elucidated in Living Animals with a Bioluminescence Reporter
Authors: Sharon L. Chinault, Julie L. Prior, Kevin M. Kaltenbronn, Anya Penly, Katherine N. Weilbaecher, David Piwnica-Worms, Kendall J. Blumer
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Inhibitors of protein prenylation, including prenyltransferase inhibitors and aminobisphosphonates such as zoledronic acid, are being investigated intensively as therapeutics in cancer and other diseases. Determining whether prenylation inhibitors directly or indirectly target tumor and/or host cells is key to understanding therapeutic mechanisms. Experimental Design: To determine which cell types can be targeted directly by distinct classes of prenylation inhibitors in vivo, we describe herein the development and implementation of a sensitive and pharmacologically specific bioluminescence-based imaging reporter that is inducible by prenylation inhibitors. Results: In mouse xenograft models of breast cancer, using reporter-bearing mammary fat pad- or bone-localized tumor cells, we show that a prenyltransferase inhibitor robustly induces reporter activity in vivo. In contrast, zoledronic acid, a bone-associated aminobisphosphonate that exerts adjuvant chemotherapeutic activity in patients with breast cancer, fails to induce reporter activity in tumor cells of either model. Conclusions: Although a prenyltransferase inhibitor can directly target breast cancer cells in vivo, zoledronic acid and related aminobisphosphonates are likely to exert antitumor activity indirectly by targeting host cells. Accordingly, these findings shift attention toward the goal of determining which host cell types are targeted directly by aminobisphosphonates to exert adjuvant chemotherapeutic activity. Clin Cancer Res; 18(15); 4136–44. ©2012 AACR.
A New Anti-Inflammatory Compound, FR167653, Ameliorates Crescentic Glomerulonephritis in Wistar-Kyoto Rats
Authors: TAKASHI WADA, KENGO FURUICHI, NORIHIKO SAKAI, YASUNORI IWATA, KEIICHI YOSHIMOTO, MIHO SHIMIZU, KEN-ICHI KOBAYASHI, NAOFUMI MUKAIDA, KOUJI MATSUSHIMA, HITOSHI YOKOYAMA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The pathophysiologic effects of FR167653 were investigated in a model of crescentic glomerulonephritis induced by a small dose of nephrotoxic serum in Wistar-Kyoto rats. The rats developed crescentic glomerulonephritis by 6 d after the administration of serum. The subcutaneous administration of FR167653 (32 mg/kg) markedly decreased the severity of the renal damage. In a group of rats treated with FR167653 daily from day 0 to day 6, glomerular damage, including crescent formation and proteinuria, was virtually absent. FR167653 markedly decreased urinary levels of monocyte chemoattractant protein-1 (MCP-1). In addition, FR167653 reduced production of MCP-1 protein and transcripts in the diseased kidneys. In a group of rats for which treatment was initiated on day 3, shortly after the appearance of glomerular abnormalities, the progression of renal disease was appreciably retarded, with partial inhibition of MCP-1. In contrast, when rats were treated only on the first day, no beneficial effects were observed and severe proliferative and necrotizing glomerulonephritis, with crescent formation, was induced by day 6, with the upregulation of MCP-1. These results suggest that FR167653 may be effective against crescentic glomerulonephritis, possibly via the inhibition of MCP-1. In addition, there was marked reduction in renal injury even when FR167653 treatment was initiated after glomerular inflammation was established, suggesting that the therapeutic application of FR167653 may be clinically useful for human renal diseases.
Zea ribosomal repeat evolution and substitution patterns
Authors: E S Buckler, T P Holtsford
Journal: Molecular Biology and Evolution (1996)

Zea and Tripsacum nuclear ribosomal internal transcribed spacer (ITS) sequences were used to evaluate patterns of concerted evolution, rates of substitutions, patterns of methylation-induced deamination, and structural constraints of the ITS. ITS pseudogenes were identified by their phylogenetic position, differences in nucleotide composition, extensive deamination at ancestral methylation sites, and substitutions resulting in low-stability secondary RNA structures. Selection was important in shaping the kinds of polymorphisms and substitutions observed in the ITS. ITS substitution rates were significantly different among the Zea taxa. Deamination of cytosines at methylation sites was a potent mutation source, but selection appeared to maintain high methylation site density throughout the ribosomal repeat except for the gene promoter. Nucleotide divergence statistics identified selectively constrained regions at the 5' ends of the ITS1 and ITS2.
A Minute of Your Time
Authors: A. I. Holleb
Journal: CA A Cancer Journal for Clinicians (1983)

Through the years I've seen a number of surveys demonstrate consistently that in the United States, family physicians enjoy a uniquely high degree of public respect and confidence.Invariably, when the credibil ity of a number of business, government, and professional people is rated, physi cians receive the highest score.With this honor comes a formidable responsibility.Are we, as physicians, really doing everything we can to earn such pub
The Tumor Suppressor Gene <b> <i>WWOX</i> </b> at <b> <i>FRA16D</i> </b> Is Involved in Pancreatic Carcinogenesis
Authors: Tamotsu Kuroki, Sai Yendamuri, Francesco Trapasso, Ayumi Matsuyama, Rami I. Aqeilan, Hansjuerg Alder, Shashi Rattan, Rossano Cesari, Maria L. Nolli, Noel N. Williams, Masaki Mori, Takashi Kanematsu, Carlo M. Croce
Journal: Clinical Cancer Research (2004)

Abstract Purpose: WWOX (WW domain containing oxidoreductase) is a tumor suppressor gene that maps to the common fragile site FRA16D. We showed previously that WWOX is frequently altered in human lung and esophageal cancers. The purpose of this study was to delineate more precisely the role of WWOX in pancreatic carcinogenesis. Experimental Design: We analyzed 15 paired pancreatic adenocarcinoma samples and 9 pancreatic cancer cell lines for WWOX alterations. Colony assay and cell cycle analysis were also performed to evaluate the role of the WWOX as a tumor suppressor gene. Results: Loss of heterozygosity at the WWOX locus was observed in 4 primary tumors (27%). Methylation analysis showed that site-specific promoter hypermethylation was detected in 2 cell lines (22%) and treatment with the demethylating agent 5-aza-2′-deoxycytidine demonstrated an increase in the expression of WWOX. In addition, 2 primary tumor samples (13%) showed promoter hypermethylation including the position of site-specific methylation. Transcripts missing WWOX exons were detected in 4 cell lines (44%) and in 2 tumor samples (13%). Real-time reverse transcription PCR revealed a significant reduction of WWOX expression in all of the cell lines and in 6 primary tumors (40%). Western blot analysis showed a significant reduction of the WWOX protein in all of the cell lines. Furthermore, transfection with WWOX inhibited colony formation of pancreatic cancer cell lines by triggering apoptosis. Conclusion: These results indicate that the WWOX gene may play an important role in pancreatic tumor development.
Loss of Cardiac Phosphoinositide 3-Kinase p110α Results in Contractile Dysfunction
Authors: Zhongju Lu, Ya-Ping Jiang, Wei Wang, Xin-Hua Xu, Richard T. Mathias, Emilia Entcheva, Lisa M. Ballou, Ira S. Cohen, Richard Z. Lin
Journal: Circulation (2009)

Phosphoinositide 3-kinase (PI3K) p110alpha plays a key role in insulin action and tumorigenesis. Myocyte contraction is initiated by an inward Ca(2+) current (I(Ca,L)) through the voltage-dependent L-type Ca(2+) channel (LTCC). The aim of this study was to evaluate whether p110alpha also controls cardiac contractility by regulating the LTCC.Genetic ablation of p110alpha (also known as Pik3ca), but not p110beta (also known as Pik3cb), in cardiac myocytes of adult mice reduced I(Ca,L) and blocked insulin signaling in the heart. p110alpha-null myocytes had a reduced number of LTCCs on the cell surface and a contractile defect that decreased cardiac function in vivo. Similarly, pharmacological inhibition of p110alpha decreased I(Ca,L) and contractility in canine myocytes. Inhibition of p110beta did not reduce I(Ca,L).PI3K p110alpha but not p110beta regulates the LTCC in cardiac myocytes. Decreased signaling to p110alpha reduces the number of LTCCs on the cell surface and thus attenuates I(Ca,L) and contractility.
Nosocomial Transmission of Human Granulocytic Anaplasmosis in China
Authors: Lijuan Zhang
Journal: JAMA (2008)

Human granulocytic anaplasmosis (HGA) is an emerging tick-borne disease in China. A cluster of cases among health care workers and family members following exposure to a patient with fulminant disease consistent with HGA prompted investigation.To investigate the origin and transmission of apparent nosocomial cases of febrile illness in the Anhui Province.After exposure to an index patient whose fatal illness was characterized by fever and hemorrhage at a primary care hospital and regional tertiary care hospital's isolation ward, secondary cases with febrile illness who were suspected of being exposed were tested for antibodies against Anaplasma phagocytophilum and by polymerase chain reaction (PCR) and DNA sequencing for A. phagocytophilum DNA. Potential sources of exposure were investigated.Cases with serological or PCR evidence of HGA were compared with uninfected contacts to define the attack rate, relative risk of illness, and potential risks for exposure during the provision of care to the index patient.In a regional hospital of Anhui Province, China, between November 9 and 17, 2006, a cluster of 9 febrile patients with leukopenia, thrombocytopenia, and elevated serum aminotransferase levels were diagnosed with HGA by PCR for A. phagocytophilum DNA in peripheral blood and by seroconversion to A. phagocytophilum. No patients had tick bites. All 9 patients had contact with the index patient within 12 hours of her death from suspected fatal HGA while she experienced extensive hemorrhage and underwent endotracheal intubation. The attack rate was 32.1% vs 0% (P = .04) among contacts exposed at 50 cm or closer, 45% vs 0% (P = .001) among those exposed for more than 2 hours, 75% vs 0% (P < .001) among those reporting contact with blood secretions, and 87.5% vs 0% (P = .004) among those reporting contact with respiratory secretions from the index patient.We report the identification of HGA in China and likely nosocomial transmission of HGA from direct contact with blood or respiratory secretions.
HIV-1 suppression during acute scrub-typhus infection
Authors: George Watt, Pacharee Kantipong, Mark de Souza, Penprapa Chanbancherd, Krisada Jongsakul, Ronnatrai Ruangweerayud, Lawrence D Loomis-Price, Victoria Polonis, Khin Saw Myint, Deborah L Birx, Arthur E Brown, Sanjeev Krishna
Journal: The Lancet (2000)
1024 GALLBLADDER CANCER IN THE NETHERLANDS: CHANGES IN INCIDENCE, TREATMENT AND SURVIVAL DURING THE LAST TWO DECADES
Authors: C.D.M. Witjes, S.A.W. van den Akker, O. Visser, H.E. Karim-Kos, E. de Vries, J.N.M. Ijzermans, R.A. de Man, J.-W. Coebergh, C. Verhoef
Journal: Journal of Hepatology (2011)
Reply to F. Tomao et al
Authors: Eric Pujade-Lauraine, Felix Hilpert, Andres Poveda
Journal: Journal of Clinical Oncology (2014)

We would like to thank Tomao et al 1 for their comments regarding our report 1a of the AURELIA randomized phase III trial evaluating the addition of bevacizumab to single-agent chemotherapy in patients with platinum-resistant ovarian cancer.We agree with Tomao et al 1 that the risk of fatal adverse events with bevacizumab does not appear to be affected by the bevacizumab regimen or administration schedule.For this reason, we chose a pragmatic bevacizumab schedule when combined with chemotherapy with the aim of minimizing inconvenience and preserving patients' quality of life, that is, 15 mg/kg every 3 weeks if chemotherapy was administered every 3 weeks or 10 mg/kg every 2 weeks if chemotherapy was delivered on days 1, 8, and 15 every 4 weeks, to avoid bevacizumab administration during the chemotherapy-free week.Tomao et al 1 question the inclusion of a weekly paclitaxel-based cohort in addition to pegylated liposomal doxorubicin (PLD) and topotecan in AURELIA.They comment that paclitaxel may be less active in patients previously treated with a paclitaxel-based regimen and that the weekly paclitaxel-bevacizumab combination may be more toxic than other single-agent chemotherapies combined with bevacizumab.This view is in contrast to several reports suggesting that weekly paclitaxel is a highly active and well-tolerated regimen in relapsed ovarian cancer, inducing significant response rates in patients whose tumors are resistant to paclitaxel administered once every 3 weeks. 24][5] In line with these data, exploratory analyses in predefined subgroups (based on stratification factors) in AURELIA showed that weekly paclitaxel was associated with a high response rate (29% with paclitaxel alone) and long median progression-free survival (3.9 months [95% CI, 3.5 to 5.6]) compared with PLD or topotecan. 6None of the deaths in the bevacizumab plus chemotherapy combination arm occurred in the weekly paclitaxel cohort.A numerical increase in the overall incidence of peripheral sensory neuropathy was detected, but may be explained by the longer duration of chemotherapy exposure associated with the strikingly prolonged progression-free survival when bevacizumab was combined with weekly paclitaxel. 6lobally, the AURELIA results provide convincing evidence for the addition of bevacizumab to all three chemotherapy agents evalu-ated.This is important, considering that many patients may not be candidates for taxane therapy.Furthermore, no increase in fatal adverse events is observed when bevacizumab is combined with weekly paclitaxel, and efficacy data strongly support the use of the paclitaxelbevacizumab combination.These results should reassure Tomao et al 1 and encourage the use of weekly paclitaxel and bevacizumab in selected patients with platinum-resistant ovarian cancer.
Fine specificity of regulatory T cells. II. Suppressor and helper T cells are induced by different regions of hen egg-white lysozyme in a genetically nonresponder mouse strain.
Authors: L Adorini, M A Harvey, A Miller, E E Sercarz
Journal: The Journal of Experimental Medicine (1979)

We have examined the ability of two purified peptide fragments derived from hen (chicken) egg-white lysozyme (HEL); N-terminal, Co-terminal peptide (a.a. 1--17:cys 6--cys 127:120--129) and mixed disulfide LII peptide (LII) (a.a. 13--105) to induce antigen-specific suppression or help in B10 (H-2b) nonresponder and B10.A (H-2a) responder mice. An anti-HEL primary in vitro antibody response can be obtained in either strain by stimulation with HEL coupled to erythrocytes (RBC). Preimmunization with HEL-complete Freund's adjuvant-(CFA) or N-C-CFA-induced suppression of the anti-HEL PFC response to HEL-RBC in spleen cell cultures from B10 mice, whereas helper activity was demonstrated in cultures from B10.A mice similarly immunized. LII-CFA priming elicited helper cells in both C57BL/10 Sn (B10) and B10.A/SgSn (B10.A) mice. The genetic nonresponsiveness of B10 mice to HEL can therefore be attributed to the activation of suppressor T cells by a limited portion of the molecule (e.g., N-C) which prevent the potential response directed against other epitopes on the same molecule (e.g., LII). One manifestation of major histocompatibility complex gene activity appears to be the intramolecular selection of different antigenic determinants leading to activation of functionally different T-cell subpopulations.
Smoking and HDL-cholesterol in a population of young male adults; study of 1954 Greek army recruits
Authors: C. Pitsavos, I. Skoumas, V. Kouloulias, M. Toutouza, A. Doulalas, S. Paximadas, N. Giotsas, S. Vaina, S. Lambrou, C. Stefanadis, P. Toutouzas
Journal: Journal of the American College of Cardiology (1998)
Evaluation of genomic high-throughput sequencing data generated on Illumina HiSeq and Genome Analyzer systems
Authors: André E Minoche, Juliane C Dohm, Heinz Himmelbauer
Journal: Genome biology (2011)

Abstract Background The generation and analysis of high-throughput sequencing data are becoming a major component of many studies in molecular biology and medical research. Illumina's Genome Analyzer (GA) and HiSeq instruments are currently the most widely used sequencing devices. Here, we comprehensively evaluate properties of genomic HiSeq and GAIIx data derived from two plant genomes and one virus, with read lengths of 95 to 150 bases. Results We provide quantifications and evidence for GC bias, error rates, error sequence context, effects of quality filtering, and the reliability of quality values. By combining different filtering criteria we reduced error rates 7-fold at the expense of discarding 12.5% of alignable bases. While overall error rates are low in HiSeq data we observed regions of accumulated wrong base calls. Only 3% of all error positions accounted for 24.7% of all substitution errors. Analyzing the forward and reverse strands separately revealed error rates of up to 18.7%. Insertions and deletions occurred at very low rates on average but increased to up to 2% in homopolymers. A positive correlation between read coverage and GC content was found depending on the GC content range. Conclusions The errors and biases we report have implications for the use and the interpretation of Illumina sequencing data. GAIIx and HiSeq data sets show slightly different error profiles. Quality filtering is essential to minimize downstream analysis artifacts. Supporting previous recommendations, the strand-specificity provides a criterion to distinguish sequencing errors from low abundance polymorphisms.
Brain-Specific Phosphorylation of MeCP2 Regulates Activity-Dependent Bdnf Transcription, Dendritic Growth, and Spine Maturation
Authors: Zhaolan Zhou, Elizabeth J. Hong, Sonia Cohen, Wen-ning Zhao, Hsin-yi Henry Ho, Lauren Schmidt, Wen G. Chen, Yingxi Lin, Erin Savner, Eric C. Griffith, Linda Hu, Judith A.J. Steen, Charles J. Weitz, Michael E. Greenberg
Journal: Neuron (2006)
Profile of soluble cytokine receptors in Crohn's disease
Authors: T Gustot
Journal: Gut (2005)

<b>Introduction:</b> Soluble cytokine receptors (sCRs) modulate the in vivo activity of cytokines. Deficient sCR production could participate in the pathogenesis and course of Crohn's disease (CD). The aim of the study was to examine the profile of sCRs in CD patients and their modulation by infliximab and corticosteroids. <b>Methods:</b> We prospectively examined active CD patients (aCD) treated with either infliximab (n = 21) or corticosteroids (n = 9), CD patients in clinical remission (rCD, n = 20), ulcerative colitis patients (UC, n = 24), and healthy subjects (HS, n = 15). Cultures of colonic biopsies were also examined from CD inflamed (n = 8), CD non-inflamed (n = 7), and healthy mucosa (n = 8). Levels of tumour necrosis factor α (TNF-α), soluble TNF receptor I (sTNFRI), soluble TNF receptor II (sTNFRII), interleukin 1β (IL-1β), soluble IL-1 receptor I (sIL-1RI), soluble IL-1 receptor II (sIL-1RII), IL-6, soluble IL-6 receptor (sIL-6R), and sgp130 were measured using ELISA. <b>Results:</b> Higher levels of sTNFRI (p&lt;0.05, p&lt;0.01), sTNFRII (p&lt;0.01, p&lt;0.01), sIL-1RI (p&lt;0.05, NS), IL-6 (p&lt;0.01, p&lt;0.01), and sIL-6R (p&lt;0.05, NS) were observed in aCD compared with rCD and HS. Interestingly, sIL-1RII (p&lt;0.05, p&lt;0.01) and sgp130 (p&lt;0.01, p&lt;0.01) were profoundly decreased in aCD compared with rCD and HS, and were negatively correlated with CRP. Deficient production of sIL-1RII was specific to CD (not observed in ulcerative colitis), and was further confirmed at the mucosal level. Infliximab decreased sTNFRII at one and four weeks (p&lt;0.05) and enhanced sIL-6R levels at one week (p&lt;0.05). Corticosteroids increased sIL-1RII levels at one week (p&lt;0.05). <b>Conclusion:</b> CD is associated with dysregulated production of sCRs. Deficiency in sIL-1RII and sgp130 may be essential to CD pathogenesis. Their replacement through the use of fusion proteins could represent future alternative therapeutic strategies for CD.