tbuckley/cabot-search huggingface dataset:
Mitochondria selective <i>S</i>‐nitrosation by mitochondria‐targeted <i>S</i>‐nitrosothiol protects against post‐infarct heart failure in mouse hearts
Authors: Carmen Methner, Edward T. Chouchani, Guido Buonincontri, Victoria R. Pell, Stephen J. Sawiak, Michael P. Murphy, Thomas Krieg
Journal: European Journal of Heart Failure (2014)

Recently it has been shown that the mitochondria-targeted S-nitrosothiol MitoSNO protects against acute ischaemia/reperfusion (IR) injury by inhibiting the reactivation of mitochondrial complex I in the first minutes of reperfusion of ischaemic tissue, thereby preventing free radical formation that underlies IR injury. However, it remains unclear how this transient inhibition of mitochondrial complex I-mediated free radicals at reperfusion affects the long-term recovery of the heart following IR injury. Here we determined whether the acute protection by MitoSNO at reperfusion prevented the subsequent development of post-myocardial infarction heart failure.Mice were subjected to 30 min left coronary artery occlusion followed by reperfusion and recovery over 28 days. MitoSNO (100 ng/kg) was applied 5 min before the onset of reperfusion followed by 20 min infusion (1 ng/kg/min). Infarct size and cardiac function were measured by magnetic resonance imaging (MRI) 24 h after infarction. MitoSNO-treated mice exhibited reduced infarct size and preserved function. In addition, MitoSNO at reperfusion improved outcome measures 28 days post-IR, including preserved systolic function (63.7 ±1.8% LVEF vs. 53.7 ± 2.1% in controls, P = 0.01) and tissue fibrosis.MitoSNO action acutely at reperfusion reduces infarct size and protects from post-myocardial infarction heart failure. Therefore, targeted inhibition of mitochondrial complex I in the first minutes of reperfusion by MitoSNO is a rational therapeutic strategy for preventing subsequent heart failure in patients undergoing IR injury.
Abstract 5523: High Glucose Promotes Intracellular Lipid Accumulation by Impairing the Balance between CD36 and ATP-Binding Cassette Transporter G1 in Vascular Smooth Muscle Cells
Authors: Jia H Xue, Zu Y Yuan, Yue Wu, Yan Zhao, Wei P Zhang, Yu L Tian, Wei M Liu, Chiharu Kishimoto
Journal: Circulation (2008)

Objective: Foam cell formation is a characteristic of atherosclerotic lesions. It’s known that high glucose promotes macrophage-derived foam cell formation involved in increased influx or reduced efflux of lipids. The aim of this study is to investigate the influence of hyperglycemia on foam cell transformation of vascular smooth muscle cells (VSMCs) and possible mechanisms contributing to these effects. Methods and Results: The results showed that high glucose in cultured human aortic SMCs increased the mRNA and protein expressions of CD36, a regulator of lipid influx, and suppressed the mRNA and protein expressions of ATP binding cassette (ABC) transporters ABCG1, a regulator of cholesterol efflux to HDL, in a dose- and time-dependent manner. However, the ability of cholesterol efflux to lipid-free apoAI was not impaired. VSMCs exposed to high glucose were easily developed into lipid-loaded cells as demonstrated by oil red O staining. Meanwhile, it had a maximum 2.3-fold increase in accumulation of esterified cholesterol compared to VSMCs cultured in normal glucose. Additionally, there was no change found in either liver X receptor (LXR)α or LXRβ, suggesting that high glucose-induced down-regulation of ABCG1 was LXR-independent. Down-regulation of ABCG1 induced by high glucose was almost totally reversed by the NF-κB inhibitors BAY 11–7085, tosyl-phenylalanine chloromethyl-ketone (TPCK) and by the antioxidant N-acetyl-L-cysteine(NAC). This reversal was accompanied by reduced intracellular lipid content. Furthermore, we also demonstrated that high glucose enhanced the binding of nuclear proteins extracted from human VSMCs to the NF-κB regulatory elements. This effect was abrogated by NAC and NF-κB inhibitors. Conclusions: These results suggested that hyperglycemia-induced foam cell formation in VSMCs was related to the imbalanced lipid flux by increasing CD36 mediated modified LDL uptake and reducing ABCG1 regulated intracellular cholesterol efflux. Moreover, this effect was associated with activated NF-κB pathway signaling.
Abstract 264: The Association of Chest Compression Fraction and Clinical Outcomes from Shockable Out-of-Hospital Cardiac Arrest During the Resuscitation Outcomes Consortium Primed Trial
Authors: Sheldon Cheskes, Robert H Schmicker, Tom Rea, Judy Powell, Ian R Drennan, Peter Kudenchuck, Christian Vaillancourt, William Conway, Ian Stiell, Dion Stubb, Dan Davis, Noah Alexander, Jim Christenson
Journal: Circulation (2014)

INTRODUCTION: The role of chest compression fraction (CCF) in resuscitation of shockable out-of-hospital cardiac arrest (OHCA) is uncertain. We evaluated the relationship between CCF and clinical outcomes in a secondary analysis of the Resuscitation Outcomes Consortium (ROC) PRIMED trial. METHODS: We included OHCA patients from the ROC PRIMED trial who suffered cardiac arrest prior to EMS arrival, presented with a shockable rhythm, and had cardiopulmonary resuscitation (CPR) process data for at least one shock. We used multivariable logistic regression adjusting for Utstein variables, CPR metrics of compression rate and perishock pause, and ROC site to determine the relationship between CCF and survival to hospital discharge, return of spontaneous circulation (ROSC), and neurologically intact survival defined with Modified Rankin Score (MRS) ≤ 3. Due to potential confounding between CCF and cases that achieved early ROSC, we also performed an analysis restricted to patients without ROSC in the first 10 minutes of EMS resuscitation. RESULTS: Among the 2,558 eligible patients, median (IQR) age was 65 (54, 76) years, 76.9% were male, and mean (SD) CCF was 0.70 (0.15). Compared to the reference group (CCF &lt; 0.60), the odds ratio (OR) for survival was 0.57 (95%CI: 0.42, 0.78) for CCF 0.60-0.79 and 0.32 (95%CI: 0.22, 0.48) for CCF ≥0.80. Results were similar for outcomes of ROSC and neurologically intact survival. Conversely, when restricted to the cohort who did not achieve ROSC during the first 10 minutes (n=1,660), the relationship between CCF and survival was no longer significant. Compared to the reference group (CCF &lt; 0.60), the OR for survival was 0.85 (95 %CI: 0.58, 1.26) for CCF 0.60-0.79 and OR 0.87 (95%CI: 0.58, 1.36) for CCF ≥0.80. CONCLUSIONS: In this observational cohort study of OHCA patients presenting in a shockable rhythm, CCF when adjusted for Utstein predictors, CPR metrics and ROC site was paradoxically associated with lower odds of survival. The relationship between CCF and clinical outcomes was null in a sensitivity analysis restricted to patients without ROSC in the first 10 minutes. CCF is a complex measure and taken by itself may not be a consistent predictor of clinical outcome.
Protection of rhesus macaques against disease progression from pathogenic SHIV-89.6PD by vaccination with phage-displayed HIV-1 epitopes
Authors: Xueni Chen, Giuseppe Scala, Ileana Quinto, Weimin Liu, Tae-Wook Chun, J. Shawn Justement, Oren J. Cohen, Tom C. vanCott, Marcin Iwanicki, Mark G. Lewis, Jack Greenhouse, Todd Barry, David Venzon, Anthony S. Fauci
Journal: Nature Medicine (2001)
A memorable patient: Repeating the tests
Authors: E. Lavendar
Journal: BMJ (1999)

Three months ago my patient had a rash on his right lower leg, which was treated initially as fungal without effect, but cleared rapidly after treatment for allergy. Two months ago, he had severe stabbing pains “like glass digging in” on his left inner arm and right shin. These pains got worse, especially at night, and became agonising. One month ago his hands and feet blew up, became red, and subsided with a scaly rash; there was a preceeding sore throat and a raised antistreptolysin O test. He had seen various doctors over the months and had now come to me.

His medical history included syphilis in the distant past; numerous negative results for VDRL …
Abstract 1841: A miR551b/catalase/MUC1/EGFR cascade for acquired apoptosis resistance and chemoresistance in lung cancer cells
Authors: Xiuling Xu, Alexandria Wells, Mabel T. Padilla, Kwang Chul Kim, Yong Lin
Journal: Cancer Research (2014)

Abstract The oncoprotein Mucin-1 (MUC1) plays multiple roles in the development of different human tumors. However, whether MUC1 is involved in acquired chemoresistance, a major challenge in cancer therapy, has not been determined. Using a lung cancer cell model with acquired apoptosis resistance (AR)-associated chemoresistance, we investigated the role and mechanism of MUC1 in acquired chemoresistance. MUC1 expression was substantially increased in cells with acquired apoptosis resistance and knockdown of MUC1 expression effectively increased sensitivity of the AR cells to apoptotic cytotoxicity induced by anticancer therapeutics, substantiating a role for MUC1 in acquired chemoresistance. Decreased hydrogen peroxide-reducing enzyme catalase and increased cellular reactive oxygen species (ROS) were found to be associated with MUC1 overexpression. Pharmacological ROS scavengers or exogenous catalase dramatically suppressed MUC1 expression, suggesting catalase suppression-mediated ROS accumulation contributes to MUC1 overexpression. Further, we found miR-551b expression was increased in the AR cells. Knockdown of miR-551b restored catalase expression, and suppressed ROS accumulation and MUC1 expression. Finally, with manipulation of MUC1 expression, we found MUC1 promotes EGFR-mediated activation of the cell survival Akt/c-FLIP/Cox2/Mcl-1 cascade and stabilization of anti-apoptosis factors c-IAP1 and c-IAP2. Thus, our results establish a role for MUC1 in acquired chemoresistance and a pathway consisting of miR-551b/catalase/ROS for MUC1overexpression, and interventions against this pathway may be exploited for overcoming acquired chemoresistance. Citation Format: Xiuling Xu, Alexandria Wells, Mabel T. Padilla, Kwang Chul Kim, Yong Lin. A miR551b/catalase/MUC1/EGFR cascade for acquired apoptosis resistance and chemoresistance in lung cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1841. doi:10.1158/1538-7445.AM2014-1841
Abstract 18980: N-terminal Region of Cardiac Myosin Binding Protein-C Regulates Sarcomeric and Cardiac Function
Authors: Diederik W Kuster, Ramzi J Khairallah, Namthip Witayavanitkul, David Barefield, Mohit Kumar, Suresh Govindan, Sivaguru Mayandi, Kyounghwan Lee, Roger Craig, Pieter P de Tombe, Sakthivel Sadayappan
Journal: Circulation (2014)

Rationale:  Cardiac myosin binding protein-C (cMyBP-C) is a trans-filament protein that can bind both the thick and thin filaments and regulate contraction. Previously we showed that decreased cMyBP-C phosphorylation is directly associated with catalytic cleavage of the first 271 residues of the N-terminal (N’) and, as a consequence, contractile dysfunction. This region has been shown to be largely responsible for the actin-myosin interacting properties of cMyBP-C and was postulated to regulate sarcomere sliding velocity. However, it is unknown whether it is necessary to regulate contractile function.   Hypothesis:  N’-region of cMyBP-C is essential for sarcomeric and cardiac function.   Methods and Results:  To determine the necessity of N’-region, we generated transgenic mice (C57BL/6) expressing a truncated 110kDa cMyBP-C lacking the first 271 amino acids (Tg110). Compared to non-transgenic litter-mates (NTG), Tg110 mice demonstrate high replacement levels of native cMyBP-C (>95%). Truncated cMyBP-C localized properly to the C-zone and there were no difference in cardiac sarcomere structure between Tg110 and NTG mice. Despite normal localization and sarcomere structure, Tg110 mouse hearts displayed overt chamber dilation and depressed ejection fraction as measured by echocardiography, with little evidence of fibrosis. Cardiac permeabilized myofilament preparations demonstrate depressed maximal force generation in Tg110 compared to NTG, with unchanged Ca 2+  sensitivity and cooperativity. Interestingly, Tg110 myofilaments displayed increased rate of cross-bridge cycling, supporting the hypothesis that the N’-region is responsible for actin interaction and acts as a viscous load on myosin heads.   Conclusion:  We show that the N’-region of cMyBP-C is indispensable for proper cardiac function. Further, we successfully demonstrate that cMyBP-C is a regulator of cardiac contractility and specifically fulfills that role via its N’-region.
Retinoids induce apoptosis in cultured keratinocytes
Authors: T.C. Islam, T. Skarin, S. Sumitran, R. Toftgård
Journal: British Journal of Dermatology (2000)

Background Apoptosis is a genetically controlled process linked to growth and differentiation, involving specific molecular and cellular events activated as a result of a variety of internal and external stimuli. Objectives To examine the ability of physiological and synthetic retinoids to induce apoptosis in the BALB/MK mouse keratinocyte cell line. Methods Cell viability was assessed by flow cytometry, various staining techniques and the TUNEL method. Results When keratinocytes were simultaneously exposed to retinoids and stimulated to differentiate at a high (1·5 mmol L−1) extracellular Ca2+ concentration over 48 h, apoptosis was induced. Of the retinoids tested, 3,4-didehydroretinoic acid and 3-methyl-tetrahydro-tetramethyl-naphthylenyl-propenyl benzoic acid were more potent than the others. In this system, the apoptosis induced by retinoids could not be correlated to the expression of tissue transglutaminase or epidermal transglutaminase. Furthermore, expression of antiapoptotic bcl-2 or proapoptotic Bax did not change significantly under the experimental conditions used, indicating that the regulation of apoptosis is complex and may be influenced by different factors. Conclusions The results suggest that retinoids activating either retinoic acid receptors or retinoid X receptors can induce apoptosis in cultured keratinocytes. Moreover, the well-established inhibitory effect of retinoids on keratinocyte differentiation implies that the apoptotic programme represents a distinct biological process.
585. Anti-Angiogenic Drugs Synergize with a Membrane Macrophage Colony Stimulating Factor (mM-CSF) Based Tumor Vaccine to Therapeutically Treat Rats with an Established Intracranial Glioma
Authors: Martin R. Jadus, Edward W. B. Jeffes, Ramon Sanchez, Christina Delgado, Jian G. Zhang, Sakineh Khalaghizadeh, Tetyana Khomenko, Animesh Petkar, Chirag Shah, Brandon Knight, Seema Vohra, Reza Jahroudi, Terry Wepsic
Journal: Molecular Therapy (2004)
Chemistry Inorganic and Organic with Experiments.
Authors: Charles Loudon Bloxam
Journal: JAMA (1923)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Maternal HIV-1 envelope–specific antibody responses and reduced risk of perinatal transmission
Authors: Sallie R. Permar, Youyi Fong, Nathan Vandergrift, Genevieve G. Fouda, Peter Gilbert, Robert Parks, Frederick H. Jaeger, Justin Pollara, Amanda Martelli, Brooke E. Liebl, Krissey Lloyd, Nicole L. Yates, R. Glenn Overman, Xiaoying Shen, Kaylan Whitaker, Haiyan Chen, Jamie Pritchett, Erika Solomon, Emma Friberg, Dawn J. Marshall, John F. Whitesides, Thaddeus C. Gurley, Tarra Von Holle, David R. Martinez, Fangping Cai, Amit Kumar, Shi-Mao Xia, Xiaozhi Lu, Raul Louzao, Samantha Wilkes, Saheli Datta, Marcella Sarzotti-Kelsoe, Hua-Xin Liao, Guido Ferrari, S. Munir Alam, David C. Montefiori, Thomas N. Denny, M. Anthony Moody, Georgia D. Tomaras, Feng Gao, Barton F. Haynes
Journal: Journal of Clinical Investigation (2015)

Despite the wide availability of antiretroviral drugs, more than 250,000 infants are vertically infected with HIV-1 annually, emphasizing the need for additional interventions to eliminate pediatric HIV-1 infections. Here, we aimed to define humoral immune correlates of risk of mother-to-child transmission (MTCT) of HIV-1, including responses associated with protection in the RV144 vaccine trial. Eighty-three untreated, HIV-1–transmitting mothers and 165 propensity score–matched nontransmitting mothers were selected from the Women and Infants Transmission Study (WITS) of US nonbreastfeeding, HIV-1–infected mothers. In a multivariable logistic regression model, the magnitude of the maternal IgG responses specific for the third variable loop (V3) of the HIV-1 envelope was predictive of a reduced risk of MTCT. Neutralizing Ab responses against easy-to-neutralize (tier 1) HIV-1 strains also predicted a reduced risk of peripartum transmission in secondary analyses. Moreover, recombinant maternal V3–specific IgG mAbs mediated neutralization of autologous HIV-1 isolates. Thus, common V3-specific Ab responses in maternal plasma predicted a reduced risk of MTCT and mediated autologous virus neutralization, suggesting that boosting these maternal Ab responses may further reduce HIV-1 MTCT.
Syphilis and gonorrhoea in men who have sex with men: a European overview
Authors: E  J Savage, G Hughes, C Ison, C  M Lowndes, Collective the European Surveillance of Sexual
Journal: Eurosurveillance (2009)

This paper describes recent trends in the epidemiology of syphilis and gonorrhoea infections in Europe among men who have sex with men (MSM). Routine surveillance data submitted to the European Surveillance of Sexually Transmitted Infections (ESSTI) network from 24 European countries for the period 1998-2007 were analysed. Data on whether syphilis and gonorrhoea infections were in MSM were available for 12 and 10 countries respectively. The number of syphilis cases reported to be MSM increased considerably in all Western European countries. While in some Central and Eastern European countries the male to female ratio remained relatively stable at around 1:1, in Slovenia and the Czech Republic the proportion of male cases increased and so did the percentage of cases reported to be MSM. More cases of gonorrhoea were seen in men than women, but the percentage of male cases reported to be MSM was lower than for syphilis. The findings suggest MSM are at high risk of STI in Western Europe and appear to be an increasingly important risk group in Central Europe. Despite this, data on infections among MSM are not collected routinely in many countries. The introduction of standardised data collection including data on diagnoses in MSM should be prioritised for monitoring STI in this population.
Ovarian Cancer Inspires Art Exhibit
Authors: Lynne Lamberg
Journal: JAMA (2005)

such damage can cause deleterious effects in the offspring, such as birth defects or childhood cancers (Aiken and Sawyer. Adv Exp Med Biol. 2003;518: 85-98). Zini noted that pregnancy is possible despite some degree of DNA damage, but little work has been done to evaluate the potential influence of sperm DNA damage on the health of resultant offspring. This may be particularly relevant for ICSI because this technique removes the natural barriers to fertilization and infertile men have higher levels of sperm DNA damage compared with fertile men. In addition, there is increasing concern regarding the safety of ICSI, which has been associated with significant increases in chromosomal abnormalities. Several studies have noted that an association may exist between ICSI and Beckwith-Wiedemann and Angelman syndromes. These are rare disorders arising fromabnormalgenetic imprinting,which is the process that silences either the maternal or paternal copy of a gene early in development (Powell. Nature. 2003;422: 656-658). “What is the implication of a successful ISCI pregnancy if you have damaged sperm DNA?” said Zini. “We don’t know the answer.”
Untitled (#B-125)
Authors: M. Therese Southgate
Journal: JAMA (2001)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Release of Fc gamma RIIa2 by activated platelets and inhibition of anti- CD9-mediated platelet aggregation by recombinant Fc gamma RIIa2
Authors: C Gachet, A Astier, H de la Salle, C de la Salle, WH Fridman, JP Cazenave, D Hanau, JL Teillaud
Journal: Blood (1995)
285. Evidence of Antiangiogenic and Antimetastatic Activities of the Recombinant Disintegrin Domain of Metargidin
Authors: Ta-Chiang Liu, Yaohe Wang, Gunnel Hallden, Jennelle Francis, Gabriel Brooks, Nick Lemoine, David Kirn
Journal: Molecular Therapy (2004)

Replication-selective oncolytic adenoviruses hold promise as a new cancer treatment platform, but novel mechanisms must be identified to maximize virus safety, potency and exogenous therapeutic gene-carrying capacity. The E1B-19kD and E3B proteins independently antagonize tumor necrosis factor (TNF-α)-mediated cell death, but their functional interactions have not been previously described. Since tumors have numerous blocks in apoptotic pathways, we hypothesized that deletion of one or both gene regions would result in cancer-selectivity in the presence of TNF-α. We therefore compared the potency and selectivity of E1B-19kD(-), E3B(-) and E1B-19kD(-)/E3B(-) mutants to wildtype adenovirus in vitro and in vivo. In cancer cells in vitro, the E1B-19kD(-) mutant had superior replication, spread and cytolysis (+) or (-) TNF-α; deletion of both E1B-19kD and E3B was relatively antagonistic. In normal cells without TNF-α, similar results were obtained. In contrast, all three mutants were dramatically inhibited in the presence of TNF-α. In immunocompetent mice, all three mutants were significantly inhibited in normal tissue compared to wildtype adenovirus. In tumors, only the E1B-19kD(-) mutant demonstrated enhanced replication, spread and antitumoral efficacy versus wildytpe. In summary, E1B-19kD-deletion plus E3B retention results in both enhanced potency and tumor necrosis factor-mediated selectivity.