tbuckley/cabot-search huggingface dataset:
Cisplatin Depletes TREX2 and Causes Robertsonian Translocations as Seen in TREX2 Knockout Cells
Authors: Ming-Jiu Chen, Lavinia C. Dumitrache, Danny Wangsa, Sheng-Mei Ma, Hesed Padilla-Nash, Thomas Ried, Paul Hasty
Journal: Cancer Research (2007)

Abstract Cisplatin, an anticancer drug, forms DNA interstrand cross-links (ICL) that interfere with replication, whereas TREX2 is a 3′→5′ exonuclease that removes 3′ mismatched nucleotides and promotes cellular proliferation. Here, we show that TREX2 is depleted in human cells derived from cancer after exposure to cisplatin but not other genotoxins including another cross-linking agent, mitomycin C (MMC), indicating a potential role for TREX2 depletion in cisplatin-induced cytotoxicity. To better understand TREX2 cellular function, we deleted TREX2 in mouse embryonic stem (ES) cells by gene targeting and find these cells exhibit reduced proliferation and gross chromosomal rearrangements including Robertsonian translocations (RbT). Quite interestingly, ES cells exposed to cisplatin also exhibit RbTs. By contrast, RbTs are not observed for ES cells exposed to MMC, indicating that RbTs are not caused by ICLs but instead TREX2 depletion by either cisplatin exposure or mutation. Taken together, our results show that cisplatin depletes TREX2 and causes genomic instability that is similarly observed in TREX2-mutant cells. Thus, cisplatin has two potential cytotoxic activities: (a) the generation of ICLs and (b) the depletion of TREX2. [Cancer Res 2007;67(19):9077–83]
The Interaction Between Signal Regulatory Protein Alpha (SIRPα) and CD47: Structure, Function, and Therapeutic Target
Authors: A. Neil Barclay, Timo K. van den Berg
Journal: Annual Review of Immunology (2013)

CD47 is a broadly expressed membrane protein that interacts with the myeloid inhibitory immunoreceptor SIRPα (also termed CD172a or SHPS-1). SIRPα is the prototypic member of the SIRP paired receptor family of closely related SIRP proteins. Engagement of SIRPα by CD47 provides a downregulatory signal that inhibits host cell phagocytosis, and CD47 therefore functions as a "don't-eat-me" signal. Here, we discuss recent structural analysis of CD47-SIRPα interactions and implications of this for the function and evolution of SIRPα and paired receptors in general. Furthermore, we review the proposed roles of CD47-SIRPα interactions in phagocytosis, (auto)immunity, and host defense, as well as its potential significance as a therapeutic target in cancer and inflammation and for improving graft survival in xenotransplantation.
Allograft Vasculopathy Versus Atherosclerosis
Authors: Maziar Rahmani, Rani P. Cruz, David J. Granville, Bruce M. McManus
Journal: Circulation Research (2006)

Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream therapy for heart failure. Approximately half of patients needing HTx have organ failure consequent to atherosclerosis. Despite advances in immunosuppressive drugs, long-term success of HTx is limited by the development of a particular type of coronary atherosclerosis, referred to as cardiac allograft vasculopathy (CAV). Although the exact pathogenesis of CAV remains to be established, there is strong evidence that CAV involves immunologic mechanisms operating in a milieu of nonimmunologic risk factors. The immunologic events constitute the principal initiating stimuli, resulting in endothelial injury and dysfunction, altered endothelial permeability, with consequent myointimal hyperplasia and extracellular matrix synthesis. Lipid accumulation in allograft arteries is prominent, with lipoprotein entrapment in the subendothelial tissue, through interactions with proteoglycans. The apparent endothelial “intactness” in human coronary arteries of the transplanted heart suggest that permeability and function of the endothelial barrier altered. Various insults to the vascular bed result in vascular smooth muscle cell (SMC) activation. Activated SMCs migrate from the media into the intima, proliferate, and elaborate cytokines and extracellular matrix proteins, resulting in luminal narrowing and impaired vascular function. Arteriosclerosis is a broad term that is used to encompass all diseases that lead to arterial hardening, including native atherosclerosis, postangioplasty restenosis, vein bypass graft occlusion, and CAV. These diseases exhibit many similarities; however, they are distinct from one another in numerous ways as well. The present review summarizes the current understanding of the risk factors and the pathophysiological similarities and differences between CAV and atherosclerosis.
Prospective Studies of Dairy Product and Calcium Intakes and Prostate Cancer Risk: A Meta-Analysis
Authors: Xiang Gao, Michael P. LaValley, Katherine L. Tucker
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: The Dietary Guidelines for Americans 2005 recommends that Americans increase their intake of dairy products. However, some studies have reported that increasing dairy product intake is associated with an increased risk of prostate cancer. We conducted a meta-analysis to examine associations between intakes of calcium and dairy products and the risk of prostate cancer. Methods: We searched Medline for prospective studies published in English-language journals from 1966 through May 2005. We identified 12 publications that used total, advanced, or fatal prostate cancer as end points and reported associations as relative risks (RRs) with 95% confidence intervals (CIs) by category of dairy product or calcium intake. Data were extracted using standardized data forms. Random-effects models were used to pool study results and to assess dose–response relationships between dairy product or calcium intakes and the risk of prostate cancer. We conducted sensitivity analyses by changing criteria for inclusion of studies or by using fixed-effects models. All statistical tests were two-sided. Results: Men with the highest intake of dairy products (RR =1.11 [95% CI = 1.00 to 1.22], P = .047) and calcium (RR = 1.39 [95% CI = 1.09 to 1.77], P = .018) were more likely to develop prostate cancer than men with the lowest intake. Dose–response analyses suggested that dairy product and calcium intakes were each positively associated with the risk of prostate cancer ( Ptrend = .029 and .014, respectively). Sensitivity analyses generally supported these associations, although the statistical significance was attenuated. The pooled relative risks of advanced prostate cancer were 1.33 (95% CI = 1.00 to 1.78; P = .055) for the highest versus lowest intake categories of dairy products and 1.46 (95% CI = 0.65 to 3.25; P >.2) for the highest versus lowest intake categories of calcium. Conclusions: High intake of dairy products and calcium may be associated with an increased risk of prostate cancer, although the increase appears to be small.
Environmental Particulate Matter and Genetic Alterations: Tarantini et al. Respond
Authors: Letizia Tarantini, Matteo Bonzini, Valeria Pegoraro, Valentina Bollati, Barbara Marinelli, Laura Cantone, Giovanna Rizzo, Pier Alberto Bertazzi, Andrea Baccarelli, Pietro Apostoli, Lifang Hou, Joel Schwartz
Journal: Environmental Health Perspectives (2009)
IL-6-mediated Th17 differentiation through RORγt is essential for the initiation of experimental autoimmune myocarditis
Authors: Tomomi Yamashita, Tomohiko Iwakura, Kazuki Matsui, Haruyo Kawaguchi, Masanori Obana, Akiko Hayama, Makiko Maeda, Yasukatsu Izumi, Issei Komuro, Yoshiyuki Ohsugi, Minoru Fujimoto, Tetsuji Naka, Tadamitsu Kishimoto, Hiroyuki Nakayama, Yasushi Fujio
Journal: Cardiovascular Research (2011)

Interleukin (IL)-17-producing helper T (Th17) cells have been proposed to participate in the pathogenesis of chronic inflammation, such as autoimmune myocarditis. IL-6 gene ablation confers the resistance to experimental autoimmune myocarditis (EAM). In this study, we have addressed the pathological roles of IL-6 in the regulation of Th17 cells in EAM. To induce EAM, mice were immunized twice with α-myosin heavy chain peptide. Three weeks after the first injection, the cardiac expression of the Th17-specific transcription factor, retinoic acid receptor-related orphan nuclear receptor (ROR γt), was up-regulated. Consistently, Th17 cells were recruited into EAM hearts, as analysed by flow cytometry. Using the mice with enhanced green fluorescence protein (eGFP) gene knocked-in at RORγt locus (RORγt-eGFP mice), we observed Th17 cell infiltration into inflamed lesions. Pre-treatment with IL-6 receptor (IL-6R)-blocking antibody (anti-IL-6R Ab) inhibited EAM induction in terms of disease severity score (3.5 ± 0.8; IgG vs. 0.5 ± 0.8; anti-IL-6R Ab, n = 6, P< 0.01) and suppressed the myocardial expression of IL-17 and RORγt. In contrast, the administration of anti-IL-6R Ab 7 days after the first immunization failed to show the inhibitory effects, suggesting that IL-6 plays important roles in EAM initiation. Finally, by generating RORγt-eGFP homozygous mice, we revealed that RORγt gene ablation conferred the resistance to EAM induction. IL-6-mediated induction of Th17 cells is critical for the onset of EAM, but not for its progression. IL-6/Th17 signalling could be a promising therapeutic target for the prevention of myocardial inflammation.
Maternal HIV Infection and Antibody Responses in Uninfected Infants—Reply
Authors: Christine E. Jones, Beate Kampmann, Anneke Hesseling
Journal: JAMA (2011)

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
Impedance pneumograph studies in left ventricular failure
Authors: A. R. Tanser
Journal: Thorax (1967)

Tidal volume can be measured by recording the change in impedance of the thorax caused by breathing. Thus breathing can be recorded quantitatively from two electrodes placed on each side of the chest. The method is especially useful in breathless patients and studies of breathing patterns during sleep. A patient with a long circulation time due to left ventricular failure had periodic breathing both awake and asleep. When asleep the respiratory minute volume was considerably reduced, and there were long apnoeic periods. This was associated with a rise in mean right atrial pressure until the patient woke with an attack of paroxysmal dyspnoea. The right atrial pressure dropped to normal when the patient breathed more regularly. Anoxia probably caused the rise in right atrial pressure. Periodic breathing disappeared when the circulation time shortened after treatment of the heart failure. The possible mechanism of these changes is discussed.
Health-Related Quality of Life and Tamoxifen in Breast Cancer Prevention: A Report From the National Surgical Adjuvant Breast and Bowel Project P-1 Study
Authors: Richard Day, Patricia A. Ganz, Joseph P. Costantino, Walter M. Cronin, D. Lawrence Wickerham, Bernard Fisher
Journal: Journal of Clinical Oncology (1999)

PURPOSE: This is the initial report from the health-related quality of life (HRQL) component of the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. This report provides an overview of HRQL findings, comparing tamoxifen and placebo groups, and advice to clinicians counseling women about the use of tamoxifen in a prevention setting. PATIENTS AND METHODS: This report covers the baseline and the first 36 months of follow-up data on 11,064 women recruited over the first 24 months of the study. Findings are presented from the Center for Epidemiological Studies–Depression Scale (CES-D), the Medical Outcomes Study 36-Item Short Form Health Status Survey (MOS SF-36) and sexual functioning scale, and a symptom checklist. RESULTS: No differences were found between placebo and tamoxifen groups for the proportion of participants scoring above a clinically significant level on the CES-D. No differences were found between groups for the MOS SF-36 summary physical and mental scores. The mean number of symptoms reported was consistently higher in the tamoxifen group and was associated with vasomotor and gynecologic symptoms. Significant increases were found in the proportion of women on tamoxifen reporting problems of sexual functioning at a definite or serious level, although overall rates of sexual activity remained similar. CONCLUSION: Women need to be informed of the increased frequency of vasomotor and gynecologic symptoms and problems of sexual functioning associated with tamoxifen use. Weight gain and depression, two clinical problems anecdotally associated with tamoxifen treatment, were not increased in frequency in this trial in healthy women, which is good news that also needs to be communicated.
Antioxidant Therapy: A New Pharmacological Approach in Shock, Inflammation, and Ischemia/Reperfusion Injury
Authors: Salvatore Cuzzocrea, Dennis P. Riley, Achille P. Caputi, Daniela Salvemini
Journal: Pharmacological Reviews (2001)

A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially superoxide and hydroxyl radical) and high-energy oxidants (such as peroxynitrite) as mediators of inflammation, shock, and ischemia/reperfusion injury. The aim of this review is to describe recent developments in the field of oxidative stress research. The first part of the review focuses on the roles of reactive oxygen species (ROS) in shock, inflammation, and ischemia/reperfusion injury. The second part of the review deals with the novel findings using recently identified pharmacological tools (e.g., peroxynitrite decomposition catalysts and selective superoxide dismutase mimetics (SODm) in shock, ischemia/reperfusion, and inflammation. 1) The role of ROS consists of immunohistochemical and biochemical evidence that demonstrates the production of ROS in shock, inflammation, and ischemia/reperfusion injury. ROS can initiate a wide range of toxic oxidative reactions. These include initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane sodium/potassium ATPase activity, inactivation of membrane sodium channels, and other oxidative modifications of proteins. All these toxicities are likely to play a role in the pathophysiology of shock, inflammation, and ischemia/reperfusion. 2) Treatment with either peroxynitrite decomposition catalysts, which selectively inhibit peroxynitrite, or with SODm, which selectively mimic the catalytic activity of the human superoxide dismutase enzymes, have been shown to prevent in vivo the delayed vascular decompensation and the cellular energetic failure associated with shock, inflammation, and ischemia/reperfusion injury. ROS (e.g., superoxide, peroxynitrite, hydroxyl radical, and hydrogen peroxide) are all potential reactants capable of initiating DNA single-strand breakage, with subsequent activation of the nuclear enzyme poly(ADP-ribose) synthetase, leading to eventual severe energy depletion of the cells and necrotic-type cell death. Antioxidant treatment inhibits the activation of poly(ADP-ribose) synthetase and prevents the organ injury associated with shock, inflammation, and ischemia/reperfusion.
<i>N</i> -Acetylcysteine Prevents the Deleterious Effect of Tumor Necrosis Factor-α on Calcium Transients and Contraction in Adult Rat Cardiomyocytes
Authors: Michel Cailleret, Aïssata Amadou, Nathalie Andrieu-Abadie, Artur Nawrocki, Christophe Adamy, Bouziane Ait-Mamar, François Rocaries, Martin Best-Belpomme, Thierry Levade, Catherine Pavoine, Françoise Pecker
Journal: Circulation (2004)

The negative effect of tumor necrosis factor-alpha (TNF-alpha) on heart contraction, which is mediated by sphingosine, is a major component in heart failure. Because the cellular level of glutathione may limit sphingosine production via the inhibition of the Mg-dependent neutral sphingomyelinase (N-SMase), we hypothesized that cardiac glutathione status might determine the negative contractile response to TNF-alpha.We examined the effects of TNF-alpha in isolated cardiomyocytes obtained from control rats or rats that were given the glutathione precursor N-acetylcysteine (NAC, 100 mg IP per animal). In cardiomyocytes obtained from control rats, 25 ng/mL TNF-alpha increased reactive oxygen species generation and N-SMase activity (500% and 34% over basal, respectively) and decreased the amplitude of [Ca(2+)](i) in response to electrical stimulation (22% below basal). NAC treatment increased cardiac glutathione content by 42%. In cardiomyocytes obtained from NAC-treated rats, 25 ng/mL TNF-alpha had no effect on reactive oxygen species production or N-SMase activity but increased the amplitude of [Ca(2+)](i) transients and contraction in response to electrical stimulation by 40% to 50% over basal after 20 minutes. This was associated with a hastened relaxation (20% reduction in t(1/2) compared with basal) and an increased phosphorylation of both Ser(16)- and Thr(17)-phospholamban residues (260% and 115% of maximal isoproterenol effect, respectively).It is concluded that cardiac glutathione status, by controlling N-SMase activation, determines the severity of the adverse effects of TNF-alpha on heart contraction. Glutathione supplementation may therefore provide therapeutic benefits for vulnerable hearts.
Automated 3D Analysis of Pre-Procedural MDCT to Predict Annulus Plane Angulation and C-Arm Positioning
Authors: Mariam Samim, Pieter R. Stella, Pierfrancesco Agostoni, Jolanda Kluin, Faiez Ramjankhan, Ricardo P.J. Budde, Gertjan Sieswerda, Emanuela Algeri, Camille van Belle, Ahmed Elkalioubie, Francis Juthier, Anouar Belkacemi, Michel E. Bertrand, Pieter A. Doevendans, Eric Van Belle
Journal: JACC. Cardiovascular imaging (2013)
The prevalence of antinuclear antibodies in patients with apparent polymorphic light eruption
Authors: G.M. MURPHY, J.L.M. HAWK
Journal: British Journal of Dermatology (1991)

Polymorphic light eruption (PLE) is a very common photosensitive disorder, the most important differential diagnosis of which is lupus erythematosus (LE). One-hundred and forty-two patients with PLE were screened for circulating antinuclear (ANA), Ro and La antibodies over a 2-year period. Results were negative in 66 patients. Sixty-two patients had low-titre ANA of various patterns, ranging from trace to 1/80 without evidence of LE although one later developed subacute cutaneous LE. Fourteen had more significant findings, six with ANA ranging from 1/160 to 1/1280 but no anti-Ro antibodies, four with ANA ranging from 1/160 to 1/1280 and also with anti-Ro antibodies and four patients with anti-Ro antibodies but low-titre ANA, one of whom later developed discoid LE. Three of these 14 patients fulfilled the American Rheumatism Association criteria for the diagnosis of systemic LE, but it was not certain in any of the patients whether the PLE-like rash represented cutaneous LE or coincidental PLE. However the overall 10% incidence of definite or possible LE in patients with suspected PLE suggests that all PLE patients should be screened for LE.
High prevalence of occult hepatitis B virus infection in children born to HBsAg-positive mothers despite prophylaxis with hepatitis B vaccination and HBIG
Authors: Sajad Shahmoradi, Yousef Yahyapour, Mahmood Mahmoodi, Seyed Moayed Alavian, Zeinab Fazeli, Seyed Mohammad Jazayeri
Journal: Journal of Hepatology (2012)
Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy
Authors: E. D. Abel, T. Doenst
Journal: Cardiovascular Research (2011)

Cardiac hypertrophy is a stereotypic response of the heart to increased workload. The nature of the workload increase may vary depending on the stimulus (repetitive, chronic, pressure, or volume overload). If the heart fully adapts to the new loading condition, the hypertrophic response is considered physiological. If the hypertrophic response is associated with the ultimate development of contractile dysfunction and heart failure, the response is considered pathological. Although divergent signalling mechanisms may lead to these distinct patterns of hypertrophy, there is some overlap. Given the close relationship between workload and energy demand, any form of cardiac hypertrophy will impact the energy generation by mitochondria, which are the key organelles for cellular ATP production. Significant changes in the expression of nuclear and mitochondrially encoded transcripts that impact mitochondrial function as well as altered mitochondrial proteome composition and mitochondrial energetics have been described in various forms of cardiac hypertrophy. Here, we review mitochondrial alterations in pathological and physiological hypertrophy. We suggest that mitochondrial adaptations to pathological and physiological hypertrophy are distinct, and we shall review potential mechanisms that might account for these differences.
Gene Flow and Natural Selection in Oceanic Human Populations Inferred from Genome-Wide SNP Typing
Authors: R. Kimura, J. Ohashi, Y. Matsumura, M. Nakazawa, T. Inaoka, R. Ohtsuka, M. Osawa, K. Tokunaga
Journal: Molecular Biology and Evolution (2008)

It is suggested that the major prehistoric human colonizations of Oceania occurred twice, namely, about 50,000 and 4,000 years ago. The first settlers are considered as ancestors of indigenous people in New Guinea and Australia. The second settlers are Austronesian-speaking people who dispersed by voyaging in the Pacific Ocean. In this study, we performed genome-wide single-nucleotide polymorphism (SNP) typing on an indigenous Melanesian (Papuan) population, Gidra, and a Polynesian population, Tongans, by using the Affymetrix 500K assay. The SNP data were analyzed together with the data of the HapMap samples provided by Affymetrix. In agreement with previous studies, our phylogenetic analysis indicated that indigenous Melanesians are genetically closer to Asians than to Africans and European Americans. Population structure analyses revealed that the Tongan population is genetically originated from Asians at 70% and indigenous Melanesians at 30%, which thus supports the so-called Slow train model. We also applied the SNP data to genome-wide scans for positive selection by examining haplotypic variation and identified many candidates of locally selected genes. Providing a clue to understand human adaptation to environments, our approach based on evolutionary genetics must contribute to revealing unknown gene functions as well as functional differences between alleles. Conversely, this approach can also shed some light onto the invisible phenotypic differences between populations.