tbuckley/cabot-search huggingface dataset:
Protein Acetylation in the Cardiorenal Axis
Authors: Erik W. Bush, Timothy A. McKinsey
Journal: Circulation Research (2010)

Abstract : Acetylation of histone and nonhistone proteins provides a key mechanism for controlling signaling and gene expression in heart and kidney. Pharmacological inhibition of protein deacetylation with histone deacetylase (HDAC) inhibitors has shown promise in preclinical models of cardiovascular and renal disease. Efficacy of HDAC inhibitors appears to be governed by pleiotropic salutary actions on a variety of cell types and pathophysiological processes, including myocyte hypertrophy, fibrosis, inflammation and epithelial-to-mesenchymal transition, and occurs at compound concentrations below the threshold required to elicit toxic side effects. We review the roles of acetylation/deacetylation in the heart and kidney and provide rationale for extending HDAC inhibitors into clinical testing for indications involving these organs.
Abstract 4469: Carbamoylating activity associated with the antitumor prodrug Laromustine inhibits angiogenesis in vitro by inducing ASK1-dependent endothelial cell death
Authors: Roxanne Ghazvinian, V. Alexandra Praggastis, Xianghong Li, Wei Zhang, Edmund J. Klinkerch, Cassandra J. Coleman, Alexendar T. Boches, Joseph A. Bellairs, Wang Min, Kevin P. Rice
Journal: Cancer Research (2011)

Abstract The prodrug Laromustine (1,2-bis[methylsulfonyl]-1-[2-chloroethyl]-2-[(methylamino) carbonyl] hydrazine; Cloretazine; VNP40101M) yields methyl isocyanate and a chloroethylating species (90CE) upon decomposition in situ. Laromustine's cytotoxicity is principally attributed to 90CE via a proposed mechanism that involves interstrand DNA cross-linking. However, the role of methyl isocyanate in the antineoplastic function has not been fully defined. A derivative of Laromustine that generates only methyl isocyanate and not the chloroethylating species, 1,2-bis[methylsulfonyl]-1-[(methylamino) carbonyl] hydrazine (101MDCE), is reported here to induce endothelial cell (EC) death through a non-apoptotic pathway at both relatively low (50 μM) and relatively high (200 μM) concentrations. 90CE, which lacks carbamoylating activity, did not induce this cell fate. 101MDCE, but not 90CE, also inhibited EC tube formation in vitro, a process involved in angiogenesis, which is critical for tumor growth and metastases. To understand the molecular mechanism for 101MDCE-induced EC death, we examined signaling pathways activated by 101DMCE in ECs. We found that 101DMCE, but not 90CE, activated JNK/p38 pathways and their upstream apoptosis activator signal-regulating kinase 1 (ASK1) using Western blot analyses. In resting ECs, ASK1 forms a complex with the reduced form of thioredoxin (Trx). The single cysteine residue in ASK1 (C250) and C32 or C35 in Trx are critical for this interaction. 101MDCE effected ASK1 dissociation from Trx, but not from the phosphoserine-binding inhibitor 14-3-3, in vitro and in vivo, consistent with the known reactivity of methyl isocyanate with the sulfhydryl groups of cysteine residues. We previously reported that the carbamoylating activity of Laromustine inhibits the enzyme Trx reductase from leukemia cell extracts. We conclude that carbamoylating agents induce ASK1-dependent EC death through dissociation of ASK1 from Trx either directly by targeting the critical Cys groups in the ASK1-Trx complex or indirectly by inhibiting Trx reductase. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4469. doi:10.1158/1538-7445.AM2011-4469
Insulin Therapy and Weight Change in Native-American NIDDM patients
Authors: Martin E Hickey, Terri R Hall
Journal: Diabetes Care (1993)

OBJECTIVE— To determine whether NIDDM patients exposed to insulin therapy in a clinical setting gain weight. RESEARCH DESIGN AND METHODS— This study, an historical cohort chart review, was conducted at the IHS clinic on the Navajo Reservation in Northern Arizona. We studied 27 Native Americans with NIDDM and 102 Native-American nondiabetic control subjects. RESULTS— Insulin therapy consisting of a mean of 105 U/day was associated with a mean weight gain of 3.0 ± 2.2 kg/yr. When insulin was discontinued or decreased, a mean weight loss of 5.2 ± 2.7 kg/yr was observed in the same patients. No significant weight gain was noted in 102 nondiabetic control subjects, nor in 20 of 27 insulin-treated patients given oral hypoglycemic agents before initial insulin therapy. CONCLUSIONS— Insulin therapy appeared to be associated with weight gain in this group of NIDDM patients. This suggests that observations for weight gain be undertaken when treating NIDDM patients with insulin, because it may exacerbate the underlying pathophysiology of the disease.
Protein Kinase R Contributes to Immunity against Specific Viruses by Regulating Interferon mRNA Integrity
Authors: Oliver Schulz, Andreas Pichlmair, Jan Rehwinkel, Neil C. Rogers, Donalyn Scheuner, Hiroki Kato, Osamu Takeuchi, Shizuo Akira, Randal J. Kaufman, Caetano Reis e Sousa
Journal: Cell Host & Microbe (2010)
Weapons of mass destruction: the greatest threat to public health
Authors: V. W. Sidel
Journal: JAMA (1989)

The role of physicians and other health workers in the preservation and promotion of peace is the most significant factor for the attainment of health for all. This 1981 resolution of the World Health Assembly (resolution WHA 34.38) recognizes that the greatest threats to the health of the people of the world lie not in specific forms of acute or chronic disease, not even in poverty, hunger, or homelessness, but rather in the consequences of war. Any war, and even preparation for war, 1 can of course lead to poverty, hunger, homelessness, and disease. Indeed, these consequences make even victory, or the quest for national security through massive arms expenditures, seem hollow. Among the dangers of war, the greatest single threat lies in weapons of indiscriminate mass destruction, whichThe Journalrecognizes annually with its Hiroshima anniversary issue.  Nuclear Weapons  Nuclear weapons remain the most potentially destructive of all these
A theoretically and practically more effective method for interruption of ventricular tachycardia: self-adapting autodecremental overdrive pacing.
Authors: G S Charos, C I Haffajee, R L Gold, R L Bishop, B V Berkovits, J S Alpert
Journal: Circulation (1986)

The efficacy and safety of a new antitachycardia pacing technique, self-adapting decremental overdrive pacing, was assessed in patients with clinical ventricular tachyarrhythmias who underwent programmed ventricular stimulation and serial drug testing. The three phases of this study involved a learning/experience phase, followed by intrapatient comparison of decremental overdrive pacing with conventional antitachycardia pacing modalities of overdrive burst ventricular pacing, and diastolic scanning with single (S2) and double (S2S3) ventricular extrastimuli. The final phase involved an intrapatient comparison of automated decremental overdrive pacing with overdrive burst ventricular pacing in patients with ventricular tachycardia (VT) cycle lengths of 280 msec or greater. Decremental overdrive pacing was superior to overdrive burst pacing and diastolic scanning (S2S3 and S2) (83% vs 38%, 50%, 9%) in patients with VT cycle lengths of 280 msec or greater. Automated decremental overdrive pacing as applied in the final phase was the most efficacious modality, terminating 92% of VT episodes compared with 56% for overdrive burst pacing in the same patients.
Physiologically based toxicokinetic modeling of 1,3-butadiene lung metabolism in mice becomes more important at low doses.
Authors: C T Evelo, J G Oostendorp, W F ten Berge, P J Borm
Journal: Environmental Health Perspectives (1993)

This paper describes a physiologically based toxicokinetic model for 1,3-butadiene uptake, distribution, and metabolic clearance in mice. Model parameters for metabolic activity were estimated from the correspondence between computer simulation studies and experimental results as published in the literature. The parameterized model was validated with independent literature data. With the resulting model, the relative importance of lung metabolism as compared to metabolism in the liver increased with decreasing ambient air concentrations. This was due to saturation of metabolism in the alveolar area of the lung, which occurred in the simulations at ambient air concentrations well below current threshold limit values. At higher air concentration, liver metabolism became relatively more important. The tendency toward increased importance of lung metabolism at low doses indicates the necessity of careful extrapolation of in vivo results to low doses. Moreover, this trend may also contribute to species difference in susceptibility to the carcinogenic activity of butadiene.
Alveolar Macrophages Are the Primary Interferon-α Producer in Pulmonary Infection with RNA Viruses
Authors: Yutaro Kumagai, Osamu Takeuchi, Hiroki Kato, Himanshu Kumar, Kosuke Matsui, Eiichi Morii, Katsuyuki Aozasa, Taro Kawai, Shizuo Akira
Journal: Immunity (2007)
Israeli government wants better monitoring of children's welfare, after three murders
Authors: J. Siegel-Itzkovich
Journal: BMJ (2008)

After the murders of three preschool children in the space of a few weeks, Israel’s government is to seek better ways to monitor children between the time they finish getting their vaccinations before the age of 2 years and their entry into kindergarten at 5 or school at 6. The mothers of two of the children have been charged with the children’s murder, while the grandfather of a third has been arrested and is expected to be charged this week.

Israeli children are not bound by law to …
A Noninvasive Isotopic Approach to Estimate the Bone Lead Contribution to Blood in Children: Implications for Assessing the Efficacy of Lead Abatement
Authors: Roberto Gwiazda, Carla Campbell, Donald Smith
Journal: Environmental Health Perspectives (2004)

Lead hazard control measures to reduce children's exposure to household lead sources often result in only limited reductions in blood lead levels. This may be due to incomplete remediation of lead sources and/or to the remobilization of lead stores from bone, which may act as an endogenous lead source that buffers reductions in blood lead levels. Here we present a noninvasive isotopic approach to estimate the magnitude of the bone lead contribution to blood in children following household lead remediation. In this approach, lead isotopic ratios of a child's blood and 5-day fecal samples are determined before and after a household intervention aimed at reducing the child's lead intake. The bone lead contribution to blood is estimated from a system of mass balance equations of lead concentrations and isotopic compositions in blood at the different times of sample collection. The utility of this method is illustrated with three cases of children with blood lead levels in the range of 18-29 microg/dL. In all three cases, the release of lead from bone supported a substantial fraction of the measured blood lead level postintervention, up to 96% in one case. In general, the lead isotopic compositions of feces matched or were within the range of the lead isotopic compositions of the household dusts with lead loadings exceeding U.S. Environmental Protection Agency action levels. This isotopic agreement underscores the utility of lead isotopic measurements of feces to identify household sources of lead exposure. Results from this limited number of cases support the hypothesis that the release of bone lead into blood may substantially buffer the decrease in blood lead levels expected from the reduction in lead intake.
Winning Health Victories with Community Commitment
Authors: Nancy Volkers
Journal: Annals of Internal Medicine (1997)

Currents15 December 1997Winning Health Victories with Community CommitmentNancy VolkersNancy VolkersSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-127-12-199712150-00051 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Improved access to health care is not the principal solution to the problem of premature deaths in poor communities, according to participants of the 1997 International Health Congress sponsored by the World Health Organization (WHO) and the state of Maryland. The remedies lie mainly in economic growth and independence, which come only with heavy involvement in planning and implementation by the people who need the help.Nearly 100 participants traveled to Baltimore in September to discuss the Healthy Cities projects, which are taking place in more than 1000 cities throughout the world (Box). The Healthy Cities concept is barely a ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 December 1997Volume 127, Issue 12Page: 1148-1149KeywordsChildrenFoodGlobal healthHealth careHealth economicsHealth promotionHealth surveysPrevention, policy, and public healthSurgeonsViolent crime Issue Published: 15 December 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Whatever Happened to Vinca-Loaded Platelets?
Authors: Wendell F. Rosse
Journal: New England Journal of Medicine (1984)

Over five years ago, Ahn and his associates published a paper on the use of platelets that had been "loaded" with vinblastine in the treatment of refractory idiopathic (immune) thrombocytopenic purpura.1 Normal platelets were incubated with vinca alkaloid, and excess drug was partially but not completely removed. The platelets were then infused into the patient. With this regimen, 6 of 11 patients had a complete remission, although 3 of the 6 had a fairly rapid relapse. Five of the six had previously responded to the intravenous administration of vincristine. Three other patients had brief partial remissions, and two patients did . . .
Exogenous Sex Hormone Exposure and the Risk for Major Malformations
Authors: Edward J. Lammer
Journal: JAMA (1986)

Several studies have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. We conducted a case-control study of first-trimester sex hormone exposure among mothers of 1,091 infants with Down syndrome or at least one of 11 major malformations. For each malformation category, the infants with other malformations served as the control group. Associations were found between esophageal atresia and any sex hormone exposure (odds ratio, 2.84); progestins (odds ratio, 2.87); nonspecified sex hormones (odds ratio, 2.99); and hormonal pregnancy tests (odds ratio, 2.81). We found no potentially confounding variables for these associations. We found no statistically significant association between any malformation category and oral contraceptive exposure. Even if the relationship between esophageal atresia and noncontraceptive sex hormone exposure is causal, the absolute risk would be low, on the order of six per 10,000 exposed live births.
Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study
Authors: Jean-Christophe Gris, Sylvie Bouvier, Nicolas Molinari, Jean-Philippe Galanaud, Éva Cochery-Nouvellon, Érik Mercier, Pascale Fabbro-Peray, Jean-Pierre Balducchi, Pierre Marès, Isabelle Quéré, Michel Dauzat
Journal: Blood (2011)
Abstract 1919: Phosphatidylserine on dying tumor cells suppresses dendritic cell activation and inhibits tumor immunity: reversal with PS-targeting antibody
Authors: Xianming Huang, Dan Ye, Philip E. Thorpe
Journal: Cancer Research (2010)

Abstract We recently showed that PS on the surface of apoptotic cancer cells can suppress recognition of tumor antigens by the immune system. It appears from work in several laboratories that dendritic cells (DC) that ingest PS-expressing tumor cells fail to mature in response to external maturation signals. In the present study, we investigated whether masking PS on apoptotic tumor cells with anti-PS antibody (2aG4) can reverse the inhibitory effect of PS on DC. Mouse bone marrow derived DC were cocultured with irradiated (PS-expressing) 4T1 breast tumor cells in the presence or absence of 2aG4. We found that: (i) masking tumor cell PS with 2aG4 increases their phagocytosis by DCs; (ii) masking tumor cell PS with 2aG4 allows DCs to mature and express immunostimulatory molecules (CD40, CD80, CD86 and MHC II); (iii) masking PS with 2aG4 decreases the production of anti-inflammatory cytokines (TGFβ and IL-10) and increases the production of inflammatory cytokines (TNFα, CCL5, IL-1β and IL-6), indicating that PS-blockade polarizes DC towards the immunostimulatory type I phenotype; (iv) immunizing mice with 2aG4-treated irradiated 4T1 cells enhances the immunogenicity of the tumor cells, rendering them resistant to rechallenge with syngeneic viable 4T1 tumor cells. These results have important implications for our understanding of the immunosuppressive effects of PS in cancer and could lead to the development of a novel whole cell cancer vaccine strategy in which PS-blocking is used to enhance immunogenicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1919.
Commentaries on this month's Controversy articles
Authors: M J LEWIS
Journal: Cardiovascular Research (1993)

Journal Article Commentaries on this month's Controversy articles Get access M J LEWIS M J LEWIS Cardiovascular Sciences Research Group, Department of' Pharmacology and Therapeutics, University of Wales College of Medicine, Heath Park, Cardiff, UK. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 12, December 1993, Pages 2283–2284, https://doi.org/10.1093/cvr/27.12.2283 Published: 01 December 1993
Cardiac Arrest after Spinal Anesthesia
Authors: Rolf Lium
Journal: New England Journal of Medicine (1946)

THE occurrence of cardiac arrest under anesthesia is fortunately extremely rare. The apparent reason is that the respiratory center is much more sensitive to anesthetic agents than is the cardiac center, so that fair warning is given of impending disaster by cessation of respiration before the heart stops.In reviewing the literature one finds a considerable number of deaths reported after spinal anesthesia. These are of two types, the immediate and the delayed. The former occur before or shortly after surgery commences. The latter may occur several hours after the patient leaves the amphitheater. This report concerns a case with . . .
Overview of a system for the computer-assisted operation of a small animal inhalation facility.
Authors: E W Van Stee, M P Moorman
Journal: Environmental Health Perspectives (1984)

Automatic monitoring of the concentration of test gases and other environmental variables in small animal inhalation exposure chambers, coupled with computing capability and feedback control of the concentration of test gas, allows almost fully automatic operation of the chambers with a minimal amount of human intervention. Time-varying exposure profiles may be generated repeatedly with great accuracy, thus allowing a more realistic simulation of real-life exposures than is approached by operating chambers manually at ostensibly constant concentrations of test gases. Carefully conducted, pre-experimental calibration procedures are performed, and daily calibration checks allow statistical control of daily chamber operation and longer term quality control. At the conclusion of each experiment the investigator is supplied with records that document chamber conditions that have been monitored throughout the entire experiment, with estimates of the accuracy that was achieved in creating the specified exposure profile. A purpose of this report is to help to bridge the gap between the practicing inhalation toxicologist and the engineer in order to encourage their cooperation and mutual understanding of the technical problems involved in developing computer-assistance packages for inhalation facilities.
<i>HER2</i>Status and Benefit from Adjuvant Trastuzumab in Breast Cancer
Authors: Soonmyung Paik, Chungyeul Kim, Norman Wolmark
Journal: New England Journal of Medicine (2008)

To the Editor: Trastuzumab, an antibody against the protein product of the human epidermal growth factor receptor type 2 (HER2) gene, improves progression-free survival and overall survival when added to chemotherapy in patients with metastatic breast cancer.1 Initial trials enrolled patients with tumors that had a staining intensity of 2+ or 3+ for HER2 on immunohistochemical analysis, but in subsequent studies, the benefit was limited to tumors with HER2 amplification as determined by fluorescence in situ hybridization (FISH). Trastuzumab also improves disease-free survival and overall survival in the adjuvant setting.2 On the basis of its mechanism of action, . . .
JAMA wants campaign on clinical alerts
Authors: D. Josefson
Journal: BMJ (1997)

The American Medical Association's journal, JAMA , is spearheading a campaign of “clinical alerts” to ensure that patients benefit quickly from medical breakthroughs.

The campaign will use established medical journals and the lay press to get the message across. The proposal was outlined by Dr George Lundberg, editor of JAMA , and Dr John Wennberg of …