tbuckley/cabot-search huggingface dataset:
Expression of CD200 on AML blasts directly suppresses memory T-cell function
Authors: S J Coles, R K Hills, E C Y Wang, A K Burnett, S Man, R L Darley, A Tonks
Journal: Leukemia (2012)

Previous studies have shown that immunosuppression in acute myeloid leukemia (AML) is associated with changes in the adaptive immune compartment. Such changes include the suppression of memory T-cell function1 and the suppression of Th1 cytokine (TNFα, IL-2 and IFNγ)-producing cells.2 A suppressed immune response in AML is associated with a worse patient outcome and increased risk of relapse,3 as well as increased risk of infection impairing patient recovery.4 The over-expression of the immunosuppressive ligand CD200 is also associated with an increased risk of relapse in AML (hazard ratio 1.7); an observation consistent with a hypothesis in which CD200 inhibits clearance of residual disease.5, 6 As memory T-cell responses are central for tumor immunosurveillance and contribute to prolonged molecular remission,7 we carried out this study to establish how these responses were affected in AML patients over-expressing CD200 (Supplemental Table S1). We initially investigated whether CD200 expression on AML blasts influenced CD8+ T-cell cytotoxic potential and the frequency of TNFα-, IL-2- and IFNγ-producing CD4+/CD8+ memory T-cells (Supplementary Materials and Methods and Supplemental Figure S1 for gating strategy). Using CD107a as a marker of cytotoxic function, AML cells were activated with PMA/ionomycin. We show that the frequency of CD107a+CD8+ memory T-cells was significantly reduced by ~50% for CD200hi patients when compared with CD200lo AML, demonstrating that cytotoxic memory T-cell activity was compromised in CD200hi patients (Figure 1a). Furthermore, the frequencies of TNFα-, IL-2- and IFNγ-producing CD4+ memory cells were also reduced by ~50% for CD200hi patients when compared with CD200lo AML (Figure 1b), significantly so in the case of IL-2 and IFNγ. Interestingly, CD200lo patients displayed a higher IFNγ response, not only with respect to CD200hi patients but also in comparison to healthy donors, suggesting a role for this cytokine in AML, which is attenuated by CD200. No difference was observed for TNFα-, IL-2- and IFNγ-producing CD8+ memory cells between CD200hi, CD200lo and healthy donors (data not shown). CD200 has also been reported to mediate suppression of the Th1 response in chronic lymphocytic leukemia as well as solid tumors,8, 9 suggesting that CD200-mediated Th1 suppression is a central mechanism in cancer immunomodulation.
Macrocytosis of the Erythrocytes
Authors: Paul G. Hattersley
Journal: JAMA (1964)

In a three-month study using precise modern laboratory techniques, macrocytosis of the erythrocytes often occurred in the absence of anemia and of the classical macrocytic diseases. Disorders in which it occurred most frequently were (1) cirrhosis, (2) malignant disease, (3) acute blood loss, and (4) megaloblastic disorders. It was found in more women than men and was most common in the elderly.
Impact of adverse events on prescribing warfarin in patients with atrial fibrillation: matched pair analysis
Authors: Niteesh K Choudhry, Geoffrey M Anderson, Andreas Laupacis, Dennis Ross-Degnan, Sharon-Lise T Normand, Stephen B Soumerai
Journal: BMJ (2006)

<h3>Abstract</h3> <b>Objectives</b> To quantify the influence of physicians9 experiences of adverse events in patients with atrial fibrillation who were taking warfarin. <b>Design</b> Population based, matched pair before and after analysis. <b>Setting</b> Database study in Ontario, Canada. <b>Participants</b> The physicians of patients with atrial fibrillation admitted to hospital for adverse events (major haemorrhage while taking warfarin and thromboembolic strokes while not taking warfarin). Pairs of other patients with atrial fibrillation treated by the same physicians were selected. <b>Main outcome measures</b> Odds of receiving warfarin by matched pairs of a given physician9s patients (one treated after and one treated before the event) were compared, with adjustment for stroke and bleeding risk factors that might also influence warfarin use. The odds of prescriptions for angiotensin converting enzyme (ACE) inhibitor before and after the event was assessed as a neutral control. <b>Results</b> For the 530 physicians who had a patient with an adverse bleeding event (exposure) and who treated other patients with atrial fibrillation during the 90 days before and the 90 days after the exposure, the odds of prescribing warfarin was 21% lower for patients after the exposure (adjusted odds ratio 0.79, 95% confidence interval 0.62 to 1.00). Greater reductions in warfarin prescribing were found in analyses with patients for whom more time had elapsed between the physician9s exposure and the patient9s treatment. There were no significant changes in warfarin prescribing after a physician had a patient who had a stroke while not on warfarin or in the prescribing of ACE inhibitors by physicians who had patients with either bleeding events or strokes. <b>Conclusions</b> A physician9s experience with bleeding events associated with warfarin can influence prescribing warfarin. Adverse events that are possibly associated with underuse of warfarin may not affect subsequent prescribing.
Pulmonary gene delivery of hybrid vector, lipopolyplex containing N-lauroylsarcosine, via the systemic route
Authors: Tomoaki Kurosaki, Reiko Kishikawa, Megumi Matsumoto, Yukinobu Kodama, Tomoyuki Hamamoto, Hideto To, Takuro Niidome, Kozo Takayama, Takashi Kitahara, Hitoshi Sasaki
Journal: Journal of Controlled Release (2009)
Selecting equipment for elderly patients in hospital.
Authors: J Andrews, L Atkinson
Journal: BMJ (1978)

The equipment used in wards caring for elderly patients, whether admission or continuing care wards, can, if correctly chosen, benefit both the elderly handicapped and the ward staff responsible for their rehabilitation. All too often, however, the wrong equipment is bought and is therefore misused or unused, either because of its inherent unsuitability or because no fore thought has been given to repair and maintenance or to the availability of spare parts. We have considered the types of ward furniture and equip ment that are essential on geriatric wards and have divided them into three categories: (a) equipment needed on admission to hospital during an acute illness; (b) equipment needed during rehabilitation; and (c) equipment for continuing care depart ments. Many of the items under each of these headings will, however, be needed throughout the patient's stay in hospital, irrespective of the type of ward. The letters in the following sections refer to the equipment listed in Appendix 1.
Fine Particle Sources and Cardiorespiratory Morbidity: An Application of Chemical Mass Balance and Factor Analytical Source-Apportionment Methods
Authors: Jeremy A. Sarnat, Amit Marmur, Mitchel Klein, Eugene Kim, Armistead G. Russell, Stefanie E. Sarnat, James A. Mulholland, Philip K. Hopke, Paige E. Tolbert
Journal: Environmental Health Perspectives (2008)

Interest in the health effects of particulate matter (PM) has focused on identifying sources of PM, including biomass burning, power plants, and gasoline and diesel emissions that may be associated with adverse health risks. Few epidemiologic studies, however, have included source-apportionment estimates in their examinations of PM health effects. We analyzed a time-series of chemically speciated PM measurements in Atlanta, Georgia, and conducted an epidemiologic analysis using data from three distinct source-apportionment methods.The key objective of this analysis was to compare epidemiologic findings generated using both factor analysis and mass balance source-apportionment methods.We analyzed data collected between November 1998 and December 2002 using positive-matrix factorization (PMF), modified chemical mass balance (CMB-LGO), and a tracer approach. Emergency department (ED) visits for a combined cardiovascular (CVD) and respiratory disease (RD) group were assessed as end points. We estimated the risk ratio (RR) associated with same day PM concentrations using Poisson generalized linear models.There were significant, positive associations between same-day PM(2.5) (PM with aero-dynamic diameter <or= 2.5 microm) concentrations attributed to mobile sources (RR range, 1.018-1.025) and biomass combustion, primarily prescribed forest burning and residential wood combustion, (RR range, 1.024-1.033) source categories and CVD-related ED visits. Associations between the source categories and RD visits were not significant for all models except sulfate-rich secondary PM(2.5) (RR range, 1.012-1.020). Generally, the epidemiologic results were robust to the selection of source-apportionment method, with strong agreement between the RR estimates from the PMF and CMB-LGO models, as well as with results from models using single-species tracers as surrogates of the source-apportioned PM(2.5) values.Despite differences among the source-apportionment methods, these findings suggest that modeled source-apportioned data can produce robust estimates of acute health risk. In Atlanta, there were consistent associations across methods between PM(2.5) from mobile sources and biomass burning with both cardiovascular and respiratory ED visits, and between sulfate-rich secondary PM(2.5) with respiratory visits.
The Scientists' Campaign Against the Strategic Defense Initiative
Authors: James H. Ransom
Journal: JAMA (1987)

<h3>To the Editor.—</h3> It is amazing to see the pages of<i>JAMA</i>(Aug 7 issue) turned over to political propaganda such as that purveyed by Kogut.<sup>1</sup>He outlines how a willful group of academicians are proceeding in their campaign to abort a feasible nuclear defense policy for the United States. Dr Kogut's article should have been entitled "The Scientists' Campaign to Weaken the Defense of America," since that is the only possible outcome of his boycott initiative. Until such time as the Soviet Union becomes a peaceful and stable society, research intended to protect us from the threat of military defeat and political domination by the Soviets is well worth our effort as well as the expense required. The Soviets' current willingness to negotiate some limits on missiles is an initial victory for the Strategic Defense Initiative (SDI), as even Dr Kogut admits. It also may be merely a
Cholesterol Lowering With Statin Drugs, Risk of Stroke, and Total Mortality
Authors: Patricia R. Hebert
Journal: JAMA (1997)

<h3>Objective.</h3> —To examine whether cholesterol lowering with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin drugs) reduces the risks of stroke and total mortality. <h3>Data Sources.</h3> —We conducted a computerized literature search from 1985 through 1995 to identify all published trials testing statin drugs. The Cholesterol and Recurrent Events (CARE) data were added after the report was published in October 1996. Our search was limited to English-language articles and included published overviews containing relevant individual trials. <h3>Trial Selection.</h3> —Criteria for inclusion of randomized trials in the overview were (1) statin drugs alone used to reduce lipid levels rather than multifactorial interventions including another type of cholesterol-lowering drug and (2) inclusion of data on deaths and/or strokes. <h3>Data Extraction.</h3> —Data were extracted by 2 researchers, and only minor discrepancies, which were easily resolved by discussion, occurred. Principal investigators of the trials and their funding agencies were also contacted to secure any relevant data not included in the published reports. <h3>Data Ssynthesis.</h3> —A total of 16 individual trials including approximately 29 000 subjects treated and followed up an average of 3.3 years were included in the overview. The average reductions in total and low-density lipoprotein cholesterol achieved were large—22% and 30%, respectively. A total of 454 strokes (fatal plus nonfatal) and 1175 deaths occurred. Those assigned to statin drugs experienced significant reductions in risks of stroke of 29% (95% confidence interval [CI], 14%-41%) as well as total mortality of 22% (95% CI, 12%-31%), which was attributable to a significant reduction in cardiovascular disease (CVD) deaths of 28% (95% CI, 16%-37%). There was no evidence of any increased risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI, 0.75-1.14). There was also no significant increase in risk of cancer (RR, 1.03; 95% CI, 0.90-1.17). <h3>Conclusion.</h3> —This overview of all published randomized trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence.
Failure of Exercise to Reduce Hypertension
Authors: Kerry J. Stewart
Journal: JAMA (1992)

To the Editor.  —In their article entitled Failure of Exercise to Reduce Blood Pressure in Patients With Mild Hypertension, Blumenthal et al 1 suggested that aerobic exercise should not be considered a replacement for pharmacological therapy in patients with mild hypertension. Because their study did not compare exercising patients with patients taking antihypertensive medication, this conclusion is overstated.  On the other hand, our study 2 of a similar group of patients with mild hypertension was a direct comparison of exercise training with concomitant use of propranolol hydrochloride, diltiazem hydrochloride, or placebo. Patients were randomized to drug therapy in a double-blinded manner. We found a mean blood pressure decrease from 145/97 to 133/84 mm Hg, with exercise training among all our patients. There were no differences among the drug or placebo groups in the magnitude of lowering blood pressure. As such, we concluded that patients who engage in exercise may not need
Learning and synaptic plasticity
Authors: G. B. Robinson
Journal: Behavioral and Brain Sciences (1997)

Controversy surrounds several experiments that have addressed whether selective synaptic strengthening occurs during learning. To date, the evidence suggests that widespread alterations in synaptic strength, through either kindling or electroconvulsive shock, can disrupt this hypothetical process. The lack of evidence for selective modification of learning through LTP stimulation, however, provides difficulties for both the prevailing hypothesis and the hypothesis advanced by Shors &amp; Matzel. Subsequent experiments may indicate a role for LTP in both learning and arousal.
Abstract 1251: Anti-cancer mechanisms of se compounds: A stable isotope-resolved metabolomic (SIRM) approach
Authors: Teresa WM Fan, Pawel Lorkiewicz, Richard M. Higashi, Andrew N. Lane
Journal: Cancer Research (2011)

Abstract Recent rapid advances in analytical tools, especially NMR and mass spectrometry, allow an unprecedented range of metabolites and their transformation pathways to be determined, which transcends classical targeted metabolic studies. We have coupled these tools with stable isotopic tracers [1-3] to investigate the anticancer efficacy and mechanism(s) of different selenium forms using lung adenocarcinoma A549 cells as a model. Selenite (SeO3), methylseleninic acid (MSA) and selenomethionine (SeM) induced distinct changes in steady-state concentrations and 13C labeling patterns of various metabolites including amino &amp; organic acids, nucleotides, antioxidants, as well as phospholipids (PL) and PL metabolites. These changes were determined using a combination of multi-nuclear 2-D NMR, GC-MS, and FT-ICR-MS techniques, which enabled perturbations in multiple metabolic pathways to be simultaneously reconstructed for relating to phenotypic changes. At low µM levels, both SeO3 and MSA inhibited growth, caused cytoskeleton disintegration, and reduced the mitochondrial redox potential in A549 cells. SeM was growth-stimulatory at ≤ 10 µM and inhibited growth but only at 40-fold higher concentration and the extent was much less than MSA or SeO3. These phenotypic differences were related to the early inhibition of glutaminolysis, Krebs cycle, and protein biosynthesis by SeO3, rapid inhibition of pyruvate carboxylation by MSA. SeM had few comparable metabolic effects. Subsequent inhibition of PL biosynthesis was also more substantial in MSA and SeO3 than in SeM-treated cells. The protein and gene expression for key enzymes in these pathways were probed to discern altered metabolic regulations. Thus, the anti-cancer action of MSA differed from that of SeO3 while SeM was not effective against lung cancer cells. The SIRM approach facilitated the resolution of the complex, form-specific anticancer mechanism of Se compounds and is generally applicable to other cancer research problems. 1. Fan, T., et al., Metabolomics-edited transcriptomics analysis of Se anticancer action in human lung cancer cells. Metabolomics Journal, 2005. 1(4): p. 325-339 2. Lane, A.N. and T.W.-M. Fan, Quantification and identification of isotopomer distributions of metabolites in crude cell extracts using 1H TOCSY. Metabolomics, 2007. 3: p. 79-86. 3. Lane, A.N., et al., Isotopomer analysis of lipid biosynthesis by high resolution mass spectrometry and NMR. Analytica Chimica Acta, 2009. 651: p. 201-208. 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 1251. doi:10.1158/1538-7445.AM2011-1251
Treatment of erythrodermic cutaneous T-cell lymphoma with extracorporeal photochemotherapy
Authors: P. Heald, A. Rook, M. Perez, B. Wintroub, R. Knobler, B. Jegasothy, F. Gasparro, C. Berger, R. Edelson
Journal: Journal of the American Academy of Dermatology (1992)

This original cohort of patients with erythrodermic cutaneous T-cell lymphoma (CTCL) was reported to have clinical improvement with photopheresis during the 12 months of the original study. No long-term follow-up data have been available to examine the impact of this therapy on the disease.Our purpose was to provide long-term follow-up on the original 29 erythrodermic CTCL patients treated with photopheresis and to compare these results with historical controls.Files of patients from the original photopheresis study centers were reviewed and their current status was documented.The median survival of the treated patients was 60.33 months from the date of diagnosis and 47.9 months from the date of the start of photopheresis therapy. A complete remission has been maintained in four of the six patients who achieved complete responses in the original study. The best responses were seen in patients with a lower CD4/CD8 ratio in the peripheral blood at the start of therapy.Photopheresis can influence the natural history of erythrodermic CTCL by inducing remissions and prolonging survival with minimal toxicity.
Vascular Endothelial Growth Factor Contributes to Prostate Cancer–Mediated Osteoblastic Activity
Authors: Yasuhide Kitagawa, Jinlu Dai, Jian Zhang, Jill M. Keller, Jacques Nor, Zhi Yao, Evan T. Keller
Journal: Cancer Research (2005)

Prostate cancer frequently metastasizes to bone resulting in the formation of osteoblastic metastases through unknown mechanisms. Vascular endothelial growth factor (VEGF) has been shown recently to promote osteoblast activity. Accordingly, we tested if VEGF contributes to the ability of prostate cancer to induce osteoblast activity. PC-3, LNCaP, and C4-2B prostate cancer cell lines expressed both VEGF-165 and VEGF-189 mRNA isoforms and VEGF protein. Prostate cancer cells expressed the mRNA for VEGF receptor (VEGFR) neuropilin-1 but not the VEGFRs Flt-1 or KDR. In contrast, mouse pre-osteoblastic cells (MC3T3-E1) expressed Flt-1 and neuropilin-1 mRNA but not KDR. PTK787, a VEGFR tyrosine kinase inhibitor, inhibited the proliferation of human microvascular endothelial cells but not prostate cancer proliferation in vitro. C4-2B conditioned medium induced osteoblast differentiation as measured by production of alkaline phosphatase and osteocalcin and mineralization of MC3T3-E1. PTK787 blocked the C4-2B conditioned medium-induced osteoblastic activity. VEGF directly induced alkaline phosphatase and osteocalcin but not mineralization of MC3T3-E1. These results suggest that VEGF induces initial differentiation of osteoblasts but requires other factors, present in C4-2B, to induce mineralization. To determine if VEGF influences the ability of prostate cancer to develop osteoblastic lesions, we injected C4-2B cells into the tibia of mice and, after the tumors grew for 6 weeks, administered PTK787 for 4 weeks. PTK787 decreased both intratibial tumor burden and C4-2B-induced osteoblastic activity as measured by bone mineral density and serum osteocalcin. These results show that VEGF contributes to prostate cancer-induced osteoblastic activity in vivo.
A History of Plastic Surgery
Authors: Matthew B. Klein
Journal: JAMA (2008)

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