tbuckley/cabot-search huggingface dataset:
Glycosylation Profile of IgG in Moderate Kidney Dysfunction
Authors: Clara Barrios, Jonas Zierer, Ivan Gudelj, Jerko Štambuk, Ivo Ugrina, Eva Rodríguez, María José Soler, Tamara Pavić, Mirna Šimurina, Toma Keser, Maja Pučić-Baković, Massimo Mangino, Julio Pascual, Tim D Spector, Gordan Lauc, Cristina Menni
Journal: Journal of the American Society of Nephrology (2015)

Glycans constitute the most abundant and diverse form of the post-translational modifications, and animal studies have suggested the involvement of IgG glycosylation in mechanisms of renal damage. Here, we explored the associations between IgG glycans and renal function in 3274 individuals from the TwinsUK registry. We analyzed the correlation between renal function measured as eGFR and 76 N-glycan traits using linear regressions adjusted for covariates and multiple testing in the larger population. We replicated our results in 31 monozygotic twin pairs discordant for renal function. Results from both analyses were then meta-analyzed. Fourteen glycan traits were associated with renal function in the discovery sample (P<6.5×10−4) and remained significant after validation. Those glycan traits belong to three main glycosylation features: galactosylation, sialylation, and level of bisecting N-acetylglucosamine of the IgG glycans. These results show the role of IgG glycosylation in kidney function and provide novel insight into the pathophysiology of CKD and potential diagnostic and therapeutic targets.
The Need for Global Action Against Multidrug-Resistant Tuberculosis
Authors: S J Heymann, T F Brewer, M E Wilson, H V Fineberg
Journal: JAMA (1999)

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Human Embryonic Stem Cell–Derived Cardiomyocytes and Cardiac Repair in Rodents
Authors: Linda W. van Laake, Robert Passier, Pieter A. Doevendans, Christine L. Mummery
Journal: Circulation Research (2008)

Cell transplantation may restore heart function in disease associated with loss or dysfunction of cardiomyocytes. Recently, Laflamme et al reported an improvement in cardiac function in immunodeficient rats 4 weeks after coronary artery ligation and injection of human embryonic stem cell-derived cardiomyocytes (hESC-CMs). We have recently carried out a comparable study transplanting hESC-CMs to the hearts of mice with myocardial infarction. Our findings were similar up to the 4-week time point, with significant improvements in cardiac function. However, our follow-up was longer, and, at 3 months, the difference between mice receiving cardiomyocytes and those receiving other cells was no longer significant. Hypothesizing that the improvement observed by Laflamme et al may have been more likely to be sustained long term because the grafts in their study appeared larger, we injected 3 times as many cells. Although this resulted in a significantly increased graft size, we again observed a functional improvement at 1 month but not at 3 months. Our results show that midterm data in these kinds of experiments must be interpreted with caution and longer-term follow-up is essential to draw conclusions on the efficacy of cardiac cell transplantation. Furthermore, our findings demonstrate the unlikely success of merely generating and injecting more cells of the same type to increase functional improvement.
Enhanced Tumor Cell Radiosensitivity and Abrogation of G2 and S Phase Arrest by the Hsp90 Inhibitor 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin
Authors: Elizabeth E. A. Bull, Hideaki Dote, Kristin J. Brady, William E. Burgan, Donna J. Carter, Michael A. Cerra, Kelli A. Oswald, Melinda G. Hollingshead, Kevin Camphausen, Philip J. Tofilon
Journal: Clinical Cancer Research (2004)

Because of the potential for affecting multiple signaling pathways, inhibition of Hsp90 may provide a strategy for enhancing tumor cell radiosensitivity. Therefore, we have investigated the effects of the orally bioavailable Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) on the radiosensitivity of human tumor cells in vitro and grown as tumor xenografts.The effect of 17-DMAG on the levels of three proteins (Raf-1, ErbB2, and Akt) previously implicated in the regulation of radiosensitivity was determined in three human solid tumor cell lines. A clonogenic assay was then used to evaluate cell survival after exposure to 17-DMAG followed by irradiation. For mechanistic insight, the G(2)- and S-phase checkpoints were evaluated in 17-DMAG-treated cells. Finally, the effect of in vivo administration of 17-DMAG in combination with radiation on the growth rate of xenograft tumors was determined.17-DMAG exposure reduced the levels of the three radiosensitivity-associated proteins in a cell line-specific manner with ErbB2 being the most susceptible. Corresponding concentrations of 17-DMAG enhanced the radiosensitivity of each of the tumor cell lines. This sensitization seemed to be the result of a 17-DMAG-mediated abrogation of the G(2)- and S-phase cell cycle checkpoints. The oral administration of 17-DMAG to mice bearing tumor xenografts followed by irradiation resulted in a greater than additive increase in tumor growth delay.These data indicate that 17-DMAG enhances the in vitro and in vivo radiosensitivity of human tumor cells. The mechanism responsible seems to involve the abrogation of radiation-induced G(2)- and S-phase arrest.
Bile salt–dependent efflux of cellular phospholipids mediated by ATP binding cassette protein B4
Authors: Shin-ya Morita, Aya Kobayashi, Yasukazu Takanezawa, Noriyuki Kioka, Tetsurou Handa, Hiroyuki Arai, Michinori Matsuo, Kazumitsu Ueda
Journal: Hepatology (2007)

Abstract Human ABCB4 (multidrug resistance [MDR]3 P-glycoprotein) is expressed in the canalicular membrane of the hepatocyte. ABCB4 has been shown to be required for phosphatidylcholine (PC) secretion into the bile and to translocate PC across the plasma membrane. To further investigate the function of ABCB4, we established a cell line stably expressing ABCB4 (human embryonic kidney [HEK]/ABCB4). The efflux of phospholipids from HEK/ABCB4 cells was remarkably increased by the addition of taurocholate. In addition, the cholesterol efflux from HEK/ABCB4 cells was also enhanced in the presence of taurocholate. Light scattering measurements suggested that the taurocholate monomer plays an important role in ABCB4-mediated lipid secretion. On the other hand, the efflux of phospholipids and cholesterol was not mediated by ABCB1 (MDR1) even in the presence of taurocholate. Taurocholate promoted the efflux of phospholipids and cholesterol from HEK/ABCB4 cells more efficiently than glycocholate and cholate. ABCB4-K435M and ABCB4-K1075M, Walker A lysine mutants, did not mediate the phospholipid and cholesterol efflux in the presence of taurocholate, suggesting that ATP hydrolysis is essential for the efflux. Verapamil completely inhibited the taurocholate-dependent efflux of phospholipids and cholesterol from HEK/ABCB4 cells. Mass spectrometry revealed that, in the presence of taurocholate, HEK/ABCB4 cells preferentially secreted PC compared to sphingomyelin. PC vesicles induced cholesterol diffusion from cell membrane, but did not accept cholesterol from ABCB4. Conclusion: ABCB4 mediates the efflux of phospholipids into the canalicular lumen in the presence of bile salts, and plays a crucial role in bile formation and lipid homeostasis. (HEPATOLOGY 2007.)
Highlights of the society for immunotherapy of cancer (SITC) 27th annual meeting
Authors: David F Stroncek, Cornelis JM Melief, Luciano Castiello, Alessandra Cesano, Martin A Cheever, Sara Civini, Begonya Comin-Anduix, Thomas F Gajewski, Philip D Greenberg, Pawel Kalinski, Howard L Kaufman, Michael H Kershaw, Samir N Khleif, Francesco Marincola, William Merritt, David H Munn, Daniel J Powell, Nicholas P Restifo, Steven A Rosenberg, Raj K Puri, Howard Streicher, Aladar A Szalay, Cassian Yee, Laurence Zitvogel, Antoni Ribas
Journal: Journal for ImmunoTherapy of Cancer (2013)

The 27<sup>th</sup> annual meeting of the Society for Immunotherapy of Cancer (SITC) was held on October 26–28, 2012 in North Bethesda, Maryland and the highlights of the meeting are summarized. The topics covered at this meeting included advances in cancer treatment using adoptive cell therapy (ACT), oncolytic viruses, dendritic cells (DCs), immune check point modulators and combination therapies. Advances in immune editing of cancer, immune modulation by cancer and the tumor microenvironment were also discussed as were advances in single cell analysis and the manufacture and potency testing of tumor infiltrating lymphocytes (TIL).
Comparing the Efficacy and Safety of a Novel Monophasic Waveform Delivered by the Passive Implantable Atrial Defibrillator With Biphasic Waveforms in Cardioversion of Atrial Fibrillation
Authors: Ganesh Manoharan, Noel Evans, Desmond Allen, John Anderson, Jennifer Adgey
Journal: Circulation (2004)

The passive implantable atrial defibrillator (PIAD) (with no battery or discharging capacitor and powered transcutaneously by radio-frequency energy) delivering a novel monophasic low-tilt waveform is more efficacious than the standard monophasic waveform at atrial defibrillation. Standard biphasic (STB) waveforms, however, are more efficacious and safer than monophasic waveforms. This study compared the efficacy and safety of the PIAD waveform with biphasic waveforms.Sustained atrial fibrillation (AF) was induced by rapid atrial pacing. Cardioversion was attempted via 2 atrial defibrillation leads. The efficacy of the PIAD was compared with 3 biphasic waveforms (standard, single rounded, and double rounded) at varying voltage settings in 10 pigs. After a synchronized shock, hemodynamic changes between the PIAD, standard biphasic, and monophasic waveforms were compared at 1.5 and 3.0 J in 12 pigs. Myocardial injury (biochemical and histological) after ten 5-J PIAD shocks was compared with a no-shock group in 14 pigs. The PIAD 100-V setting was significantly more efficacious than the STB (100/-50 V: 100% [1.88+/-0.02 J] versus 90% [0.89+/-0.0 J]; P=0.025). No arrhythmic, hemodynamic, or myocardial injury was observed with the PIAD waveform.Defibrillation with the PIAD is more efficacious than with the STB waveform and appears safe. This device could provide a more effective option for cardioversion.
A Study of the Process of Emergency Psychotherapy
Authors: THOMAS N. RUSK, ROBERT H. GERNER
Journal: American Journal of Psychiatry (1972)

The authors studied the relationship between the amount of therapist talk time during crisis session interviews and the relief of distress in 38 emergency room patients. They found that in the sessions judged as successful the therapists talked significantly less in the first third of the interviews and significantly more in the last third and had larger increases in the amount of talk time from the first to the last third.
Intensive livestock operations, health, and quality of life among eastern North Carolina residents.
Authors: S Wing, S Wolf
Journal: Environmental Health Perspectives (2000)

People who live near industrial swine operations have reported decreased health and quality of life. To investigate these issues, we surveyed residents of three rural communities, one in the vicinity of an approximately 6,000-head hog operation, one in the vicinity of two intensive cattle operations, and a third rural agricultural area without livestock operations that use liquid waste management systems. Trained interviewers obtained information about health symptoms and reduced quality of life during the previous 6 months. We completed 155 interviews, with a refusal rate of 14%. Community differences in the mean number of episodes were compared with adjustment for age, sex, smoking, and employment status. The average number of episodes of many symptoms was similar in the three communities; however, certain respiratory and gastrointestinal problems and mucous membrane irritation were elevated among residents in the vicinity of the hog operation. Residents in the vicinity of the hog operation reported increased occurrences of headaches, runny nose, sore throat, excessive coughing, diarrhea, and burning eyes as compared to residents of the community with no intensive livestock operations. Quality of life, as indicated by the number of times residents could not open their windows or go outside even in nice weather, was similar in the control and the community in the vicinity of the cattle operation but greatly reduced among residents near the hog operation. Respiratory and mucous membrane effects were consistent with the results of studies of occupational exposures among swine confinement-house workers and previous findings for neighbors of intensive swine operations. Long-term physical and mental health impacts could not be investigated in this study.
Prognostic Factors and Outcome of Human Herpesvirus 8–Associated Primary Effusion Lymphoma in Patients With AIDS
Authors: Emmanuelle Boulanger, Laurence Gérard, Jean Gabarre, Jean-Michel Molina, Christophe Rapp, Jean-François Abino, Jacques Cadranel, Sylvie Chevret, Eric Oksenhendler
Journal: Journal of Clinical Oncology (2005)

Primary effusion lymphoma (PEL) is a rare high-grade B-cell non-Hodgkin's lymphoma associated with Kaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) infection, and is mostly observed in the course of HIV infection. The prognosis is poor, with reported median survival time shorter than 6 months. To date, no prognostic factor has been identified in this subset of lymphoma.We describe here a large series of HIV-infected patients with PEL, including 28 cases diagnosed in six centers during an 11-year time period. Prognosis analysis was performed using a Cox proportional hazard regression model. Statistically significant covariates were further analyzed in a forward, stepwise multivariate model.After a median follow-up of 3.8 years (range, 10 months to 10.8 years), nine patients (32%) were still alive, and eight of them remained progression free. The median survival was 6.2 months, and the 1-year overall survival rate was 39.3%. Fourteen patients (50%) achieved complete remission, with a 1-year disease-free survival rate at 78.6%. In a multivariate analysis, only a performance status more than 2 (hazard ratio, 5.84; 95% CI, 1.76 to 19.33) and the absence of highly active antiretroviral therapy (HAART) before PEL diagnosis (hazard ratio, 3.26; 95% CI, 1.14 to 9.34) were found to be independent predictors for shorter survival.Based on a retrospective series of 28 patients, two prognostic factors were identified as being independently associated with impaired clinical outcome in HIV-related PEL--(1) a poor performance status and (2) the absence of HAART before PEL diagnosis.
Phase I Active Immunotherapy With Combination of Two Chimeric, Human Epidermal Growth Factor Receptor 2, B-Cell Epitopes Fused to a Promiscuous T-Cell Epitope in Patients With Metastatic and/or Recurrent Solid Tumors
Authors: Pravin T.P. Kaumaya, Kevin Chu Foy, Joan Garrett, Sharad V. Rawale, Daniele Vicari, Jennifer M. Thurmond, Tammy Lamb, Aruna Mani, Yahaira Kane, Catherine R. Balint, Donald Chalupa, Gregory A. Otterson, Charles L. Shapiro, Jeffrey M. Fowler, Michael R. Grever, Tanios S. Bekaii-Saab, William E. Carson
Journal: Journal of Clinical Oncology (2009)

PURPOSE To evaluate the maximum-tolerated dose (MTD), safety profile, and immunogenicity of two chimeric, B-cell epitopes derived from the human epidermal growth factor receptor (HER2) extracellular domain in a combination vaccine with a promiscuous T-cell epitope (ie, MVF) and nor-muramyl-dipeptide as adjuvant emulsified in SEPPIC ISA 720. PATIENTS AND METHODS Eligible patients with metastatic and/or recurrent solid tumors received three inoculations on days 1, 22, and 43 at doses of total peptide that ranged from 0.5 to 3.0 mg. Immunogenicity was evaluated by enzyme-linked immunosorbent assay, flow cytometry, and HER2 signaling assays. Results Twenty-four patients received three inoculations at the intended dose levels, which elicited antibodies able to recognize native HER2 receptor and inhibited both the proliferation of HER2-expressing cell lines and phosphorylation of the HER2 protein. The MTD was determined to be the highest dose level of 3.0 mg of the combination vaccine. There was a significant increase from dose level 1 (0.5 mg) to dose level 4 (3.0 mg) in HER2-specific antibodies. Four patients (one each with adrenal, colon, ovarian, and squamous cell carcinoma of unknown primary) were judged to have stable disease; two patients (one each with endometrial and ovarian cancer) had partial responses; and 11 patients had progressive disease. Patients with stable disease received 6-month boosts, and one patient received a 20-month boost. CONCLUSION The combination vaccines were safe and effective in eliciting antibody responses in a subset of patients (62.5%) and were associated with no serious adverse events, autoimmune disease, or cardiotoxicity. There was preliminary evidence of clinical activity in several patients.
Localized avascular necrosis of lesser curve of stomach complicating highly selective vagotomy.
Authors: J F Halvorsen, P Heimann, J H Solhaug, K B Jacobsen
Journal: BMJ (1975)

The fourth case of localized avascular necrosis of the lesser curve of the stomach after highly selective vagotomy is reported. The pathogeneses was probably related to the relative poverty of the submucosal blood supply along the lesser curve. This complication may be prevented by peritonealizing the lesser curve before closing the abdominal wall.
Ca <sup>2+</sup> /Calmodulin–Dependent Protein Kinase Modulates Cardiac Ryanodine Receptor Phosphorylation and Sarcoplasmic Reticulum Ca <sup>2+</sup> Leak in Heart Failure
Authors: Xun Ai, Jerry W. Curran, Thomas R. Shannon, Donald M. Bers, Steven M. Pogwizd
Journal: Circulation Research (2005)

Abnormal release of Ca from sarcoplasmic reticulum (SR) via the cardiac ryanodine receptor (RyR2) may contribute to contractile dysfunction and arrhythmogenesis in heart failure (HF). We previously demonstrated decreased Ca transient amplitude and SR Ca load associated with increased Na/Ca exchanger expression and enhanced diastolic SR Ca leak in an arrhythmogenic rabbit model of nonischemic HF. Here we assessed expression and phosphorylation status of key Ca handling proteins and measured SR Ca leak in control and HF rabbit myocytes. With HF, expression of RyR2 and FK-506 binding protein 12.6 (FKBP12.6) were reduced, whereas inositol trisphosphate receptor (type 2) and Ca/calmodulin–dependent protein kinase II (CaMKII) expression were increased 50% to 100%. The RyR2 complex included more CaMKII (which was more activated) but less calmodulin, FKBP12.6, and phosphatases 1 and 2A. The RyR2 was more highly phosphorylated by both protein kinase A (PKA) and CaMKII. Total phospholamban phosphorylation was unaltered, although it was reduced at the PKA site and increased at the CaMKII site. SR Ca leak in intact HF myocytes (which is higher than in control) was reduced by inhibition of CaMKII but was unaltered by PKA inhibition. CaMKII inhibition also increased SR Ca content in HF myocytes. Our results suggest that CaMKII-dependent phosphorylation of RyR2 is involved in enhanced SR diastolic Ca leak and reduced SR Ca load in HF, and may thus contribute to arrhythmias and contractile dysfunction in HF.
G.P. Merit Awards
Authors: S. Mark, K. Hardy, H. H. Goodman, S. G. Ashman, S. Steel, E. Silver, J. W. Miller, D. Kelly, R. I. S. Lewis, M. W. Johnston, E. C. Ramsey, D. C. Bell, N. H. Lawrence, R. Birk, S. Osborne, B. Cameron, J. H. Craig, M. J. Fry, W. H. Raine, J. Woolf, W. E. Hay, T. M. C. Saint, W. Sandford, H. C. Cowling, J. Wright, G. H. Cottrell, K. S. Dawes, A. J. G. Wilson, R. J. Dias
Journal: BMJ (1967)
Endoscopic retrograde cholangiography and endoscopic papillotomy in patients with a previous Billroth-II resection.
Authors: M Osnes, A R Rosseland, L Aabakken
Journal: Gut (1986)

Methods for endoscopic retrograde cholangiography (ERC) and endoscopic papillotomy (EPT) in patients with Billroth-II operations are described, and experience with their use during the last four years (since 1980) is presented. Endoscopic retrograde cholangiopancreatography was successful in 134 of 147 patients (92%) and endoscopic papillotomy was successful in 46 of 50 patients. The described methods were used in two different hospitals by two different endoscopists and there was no difference in the results. We conclude that patients with a Billroth-II operation may undergo endoscopic diagnostic as well as therapeutic procedures with a high rate of success, with similar results as in ordinary patients and with no greater risk of complications.