tbuckley/cabot-search huggingface dataset:
Prevalence and determinants of antibodies to hepatitis C virus and markers for hepatitis B virus infection in patients with HIV infection in Aquitaine
Authors: F Saillour, F Dabis, M Dupon, D Lacoste, P Trimoulet, P Rispal, E Monlun, J-M Ragnaud, P Morlat, J-L Pellegrin, H Fleury, P Couzigou
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To evaluate the prevalence of antibodies to hepatitis C virus and serological markers for hepatitis B virus infection in patients with HIV. <b>Design</b>: Cross sectional survey. <b>Setting</b>: Aquitaine, southwestern France, 1991-94. <b>Subjects</b>: 1935 HIV positive patients seen at least once since June 1991. <b>Main outcome measures</b>: Presence of antibodies to hepatitis C virus were detected by second or third generation enzyme linked immunosorbent assay (ELISA) and recombinant immunoblot assay (RIBA) and markers for hepatitis B virus detected by ELISA. <b>Results</b>: The prevalence was 42.5% (823) for antibodies to hepatitis C virus, 56.4 (507) for antibodies to hepatitis B core antigen, 6.9% (133) for hepatitis B surface antigen, 30.2% (584) for antibodies to hepatitis B core and surface antigen with no detectable surface antigen, 26.2% (507) for antibodies to core antigen only, and 4.8% (92) for antibodies to surface antigen only. The prevalence of antibodies to hepatitis C virus was 86.1% (726/843) in subjects who had bloodborne HIV infection and 7.3% (66/899) in those with sexually acquired infection. The prevalence of markers for hepatitis B was higher among homosexuals than in the other groups of patients, except for antibodies to surface antigen alone. The relation between markers for hepatitis B and hepatitis C virus was negative among men but positive among women. <b>Conclusions</b>: The results favour the hypothesis that hepatitis C virus is sexually transmitted much less commonly than either HIV or hepatitis B virus.
Tissue factor expression by endothelial cells in sickle cell anemia.
Authors: A Solovey, L Gui, N S Key, R P Hebbel
Journal: Journal of Clinical Investigation (1998)

The role of the vascular endothelium in activation of the coagulation system, a fundamental homeostatic mechanism of mammalian biology, is uncertain because there is little evidence indicating that endothelial cells in vivo express tissue factor (TF), the system's triggering mechanism. As a surrogate for vessel wall endothelium, we examined circulating endothelial cells (CEC) from normals and patients with sickle cell anemia, a disease associated with activation of coagulation. We find that sickle CEC abnormally express TF antigen (expressed as percent CEC that are TF-positive), with 66+/-13% positive in sickle patients in steady-state, 83+/-19% positive in sickle patients presenting with acute vasoocclusive episodes, and only 10+/-13% positive in normal controls. Repeated samplings confirmed this impression that TF expression is greater when sickle patients develop acute vasoocclusive episodes. Sickle CEC are also positive for TF mRNA, with excellent concurrence between antigen and mRNA expression. The TF expressed on the antigen-positive CEC is functional, as demonstrated by a binding assay for Factor VIIa and a chromogenic assay sensitive to generation of Factor Xa. By establishing that endothelial cells in vivo can express TF, these data imply that the vast endothelial surface area does provide an important pathophysiologic trigger for coagulation activation.
SUSTAINED BACTEREMIA WITH PLEUROPNEUMONIA-LIKE ORGANISMS IN A POSTPARTUM PATIENT
Authors: D. Ward Slingerland
Journal: JAMA (1952)

Since the first isolation of pleuropneumonia-like organisms (PPLO) from man in 1937 by Dienes and Edsall,<sup>1</sup>these organisms have been cultured from the genitourinary tract, joints, sputum, and spinal fluid of patients.<sup>2</sup>Only one possible instance of the isolation of pleuropneumonia-like organisms from the blood has appeared in the report of the cultivation of an unusual organism from the blood of a patient with subacute bacterial endocarditis.<sup>3</sup>However, this organism was described as resembling either the Grahamella organism (Tyzzer) or a pleuropneumonia-like organism, and, on the basis of its described characteristics, it would not seem to be a pleuropneumonia-like organism.<sup>4</sup> The clinical course and laboratory findings in a patient with a febrile illness accompanied by sustained bacteremia, during which pleuropneumonia-like organisms were repeatedly isolated from the blood stream, are reported here. <h3>REPORT OF A CASE</h3> A 16-year-old Negro girl was admitted to the obstetric service of
Safety Outcomes in Meta-analyses of Phase 2 vs Phase 3 Randomized Trials
Authors: John W. Eikelboom, Shamir R. Mehta, Janice Pogue, Salim Yusuf
Journal: JAMA (2001)

ContextRecent studies have reported disagreement between meta-analysis of small trials and subsequent large trials addressing the same question. However, disagreement for uncommon but serious adverse safety outcomes has not been examined.ObjectiveTo explore disagreement for serious adverse safety (intracranial hemorrhage [ICH]) and efficacy outcomes between meta-analysis of phase 2 (small) vs meta-analysis of phase 3 (large) randomized controlled trials comparing the efficacy of bolus thrombolytic therapy with infusion for acute myocardial infarction (AMI).Data SourcesElectronic databases (MEDLINE, Cochrane Database of Clinical Trials) between January 1980 and December 1999 using the search terms thrombolysis, thrombolytic therapy, and myocardial infarction; conference proceedings; and reference lists.Study SelectionFifteen randomized trials comparing thrombolytic agents administered by bolus injection with standard infusion therapy in patients with AMI.Data ExtractionData on ICH, other causes of stroke, total mortality, and reinfarction were independently extracted from each study by 2 observers.Data SynthesisMeta-analysis of 9 phase 2 trials (n = 3956) revealed a lower risk of ICH with bolus thrombolytic therapy (odds ratio [OR], 0.53; 95% confidence interval [CI], 0.27-1.01), which was not statistically significant. Meta-analysis of 6 phase 3 trials (n = 62 673) indicated a significant increase in risk of ICH (OR, 1.25; 95% CI, 1.06-1.49). These results were significantly different (P = .01). There was no disagreement for efficacy outcomes. Phase 2 trials included younger and heavier patients with lower baseline blood pressures, and were more often open-label. Subgroup analyses suggested that each of these factors was associated with a lower estimate of risk of ICH with bolus agents.ConclusionsOur results suggest that when therapeutic interventions are associated with a potential for uncommon but serious adverse safety outcomes, there may be differences between small phase 2 and large phase 3 trials that result in their disagreement for safety but not necessarily efficacy outcomes. Further investigation of the frequency and causes of disagreement between small and large trials for safety outcomes is warranted.
<i>Trans</i>-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in U.S. Adults
Authors: Dariush Mozaffarian, Haiming Cao, Irena B. King, Rozenn N. Lemaitre, Xiaoling Song, David S. Siscovick, Gökhan S. Hotamisligil
Journal: Annals of Internal Medicine (2010)

Background: Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. Objective: To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes. Design: Prospective cohort study from 1992 to 2006. Setting: Four U.S. communities. Patients: 3736 adults in the Cardiovascular Health Study. Measurements: Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose–insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women. Results: In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (−19.0%; P < 0.001), a lower total cholesterol–HDL cholesterol ratio (−4.7%; P < 0.001), lower C-reactive protein levels (−13.8%; P = 0.05), and lower insulin resistance (−16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort. Limitation: Results could be affected by measurement error or residual confounding. Conclusion: Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation. Primary Funding Source: National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.
Tumor Suppressor VDUP1 Increases p27kip1 Stability by Inhibiting JAB1
Authors: Jun-Ho Jeon, Kee-Nyung Lee, Chae Young Hwang, Ki-Sun Kwon, Kwan-Hee You, Inpyo Choi
Journal: Cancer Research (2005)

Vitamin D3 up-regulated protein 1 (VDUP1) is a stress-response gene that is up-regulated by 1,25(OH)2D3 in many cells. It has been reported that VDUP1 expression is reduced in many tumor cells and the enforced expression of VDUP1 inhibits cell proliferation by arresting cell cycle progression. Here, we found that VDUP1-/- fibroblast cells proliferated more rapidly compared with wild-type cells with reduced expression of p27(kip1), a cyclin-dependent kinase inhibitor. JAB1 is known to interact with p27(kip1) and to decrease the stability of p27(kip1). VDUP1 interacted with JAB1 and restored JAB1-induced suppression of p27(kip1) stability. In this process, VDUP1 blocked the JAB1-mediated translocation of p27(kip1) from the nucleus to the cytoplasm. In addition, VDUP1 inhibited JAB1-mediated activator protein-1 activation and cell proliferation. Taken together, these results indicate that VDUP1 is a novel factor of p27(kip1) stability via regulating JAB1.
Abstract 3410: A novel regulatory region of the MYC oncogene decreases Myc transcriptional activity
Authors: Manpreet Kalkat, Amanda Wasylishen, Pak-Kei Michael Chan, Aleksandra Pandyra, Sam Sulgi Kim, Christina Bros, Brian Raught, Linda Z. Penn
Journal: Cancer Research (2014)

Abstract MYC is a transcription factor that contributes to over 50% of cancers. While deregulated protein expression of MYC is an important factor driving tumorigenesis, remarkably little is known about the post-translational modifications (PTMs) that are necessary for MYC to function as an active oncogene. Given the important role of PTMs in the regulation of protein activity and stability, our overall objective is to further characterize novel PTMs of MYC, and the functional contribution of these modifications to the ability of the MYC to transform cells. Using a structure-function approach, we have identified six C-terminal lysines that can modulate the ability of MYC to transform cells. By utilizing lysine to arginine mutations (6KR) to abrogate signaling through these residues, we show that MYC 6KR increases anchorage-independent colony growth compared with MYC-WT. Moreover, this mutant was also more potent than WT in promoting xenograft tumour growth. Through target gene expression analysis and luciferase reporter assays, we show that 6KR has enhanced transcriptional activity compared with MYC-WT. To characterize the modifications that can occur at these lysine residues, we have performed mass spectrometry analysis and have identified a number of PTMs that can occur in this region. Furthermore, we have conducted BioID to identify MYC interactors that change in association with 6KR MYC compared to MYC-WT. We theorize that identifying the signaling pathways leading to post-translational modification of this region will be an important first step in the development of inhibitors targeting MYC induced transformation. Citation Format: Manpreet Kalkat, Amanda Wasylishen, Pak-Kei Michael Chan, Aleksandra Pandyra, Sam Sulgi Kim, Christina Bros, Brian Raught, Linda Z. Penn. A novel regulatory region of the MYC oncogene decreases Myc transcriptional activity. [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 3410. doi:10.1158/1538-7445.AM2014-3410
Nitrite Anion Provides Potent Cytoprotective and Antiapoptotic Effects as Adjunctive Therapy to Reperfusion for Acute Myocardial Infarction
Authors: Felix M. Gonzalez, Sruti Shiva, Pamela S. Vincent, Lorna A. Ringwood, Li-Yueh Hsu, Yuen Yi Hon, Anthony H. Aletras, Richard O. Cannon, Mark T. Gladwin, Andrew E. Arai
Journal: Circulation (2008)

Accumulating evidence suggests that the ubiquitous anion nitrite (NO2-) is a physiological signaling molecule, with roles in intravascular endocrine nitric oxide transport, hypoxic vasodilation, signaling, and cytoprotection. Thus, nitrite could enhance the efficacy of reperfusion therapy for acute myocardial infarction. The specific aims of this study were (1) to assess the efficacy of nitrite in reducing necrosis and apoptosis in canine myocardial infarction and (2) to determine the relative role of nitrite versus chemical intermediates, such as S-nitrosothiols.We evaluated infarct size, microvascular perfusion, and left ventricular function by histopathology, microspheres, and magnetic resonance imaging in 27 canines subjected to 120 minutes of coronary artery occlusion. This was a blinded, prospective study comparing a saline control group (n=9) with intravenous nitrite during the last 60 minutes of ischemia (n=9) and during the last 5 minutes of ischemia (n=9). In saline-treated control animals, 70+/-10% of the area at risk was infarcted compared with 23+/-5% in animals treated with a 60-minute nitrite infusion. Remarkably, a nitrite infusion in the last 5 minutes of ischemia also limited the extent of infarction (36+/-8% of area at risk). Nitrite improved microvascular perfusion, reduced apoptosis, and improved contractile function. S-Nitrosothiol and iron-nitrosyl-protein adducts did not accumulate in the 5-minute nitrite infusion, suggesting that nitrite is the bioactive intravascular nitric oxide species accounting for cardioprotection.Nitrite has significant potential as adjunctive therapy to enhance the efficacy of reperfusion therapy for acute myocardial infarction.
Surgical Management of Aortic Dissection During a 30-Year Period
Authors: James I. Fann, Julian A. Smith, D. Craig Miller, R. Scott Mitchell, Kathleen A. Moore, Gary Grunkemeier, Edward B. Stinson, Philip E. Oyer, Bruce A. Reitz, Norman E. Shumway
Journal: Circulation (1995)

Certain recent studies have demonstrated improved surgical outcome in patients with aortic dissection. We analyzed the surgical survival rates of patients with acute aortic dissections and the late prognosis of those with aortic dissection during a 30-year period.Between 1963 and 1992, 360 patients (256 men and 104 women; mean +/- 1 SD age, 57 +/- 14 years) underwent surgery for aortic dissection: 174 patients had an acute type A (AcA), 46 an acute type B (AcB), 106 a chronic type A (ChA), and 34 a chronic type B (ChB) aortic dissection. The overall operative mortality rate was 24 +/- 8% (26 +/- 3% for AcA, 39 +/- 8% for AcB, 17 +/- 4% for ChA, and 15 +/- 6% for ChB, [+/- 70% confidence limit]). The operative mortality rates for patients with acute aortic dissection (AcA or AcB) were assessed for five time "windows": 1963 to 1972 (42 +/- 8%), 1973 to 1977 (37 +/- 8%), 1978 to 1982 (15 +/- 6%), 1983 to 1987 (27 +/- 6%), and 1988 to 1992 (26 +/- 6%). Logistic regression analysis suggested that the low operative mortality rate during the 1978-to-1982 interval occurred by chance. Multivariate analysis showed earlier operative year, hypertension, cardiac tamponade, renal dysfunction, and older age were independent determinants of operative death. Actuarial survival rates (including early deaths) after 5, 10, and 15 years for AcA patients were 55%, 37%, and 24%; for AcB, 48%, 29%, and 11%; for ChA, 65%, 45%, and 27%; and for ChB, 59%, 45%, and 27%. Multivariate analysis revealed that older age and previous operation were significant predictors for late death. Freedom from reoperation for all patients was 84%, 67%, and 57% at 5, 10, and 15 years, respectively.Although the operative mortality rate decreased over time for patients with aortic dissection, the risk for those with acute aortic dissection during the last 10 years (1983 to 1992) is probably more realistic than that observed in the preceding 5-year interval (1978 to 1982). The operative mortality rates for patients with chronic aortic dissection have remained relatively static. Earlier diagnosis of acute aortic dissection before development of cardiac tamponade and renal impairment is critical to improve the operative salvage rate. Long-term outcome still is not optimal, which emphasizes the need for better serial postoperative aortic imaging surveillance and medical follow-up and blood pressure control.
CDKN2A promoter hypermethylation in astrocytomas is associated with age and sex
Authors: Markênia Kélia Santos Alves, Mário Henrique Girão Faria, Eduardo Henrique Cunha Neves Filho, Adriana Camargo Ferrasi, Maria Inês de Moura Campos Pardini, Manoel Odorico de Moraes Filho, Silvia Helena Barem Rabenhorst
Journal: International Journal of Surgery (2013)
Cytogenetic effects from exposure to mixed pesticides and the influence from genetic susceptibility.
Authors: W W Au, C H Sierra-Torres, N Cajas-Salazar, B K Shipp, M S Legator
Journal: Environmental Health Perspectives (1999)

Exposure to pesticides remains a major environmental health problem. Health risk from such exposure needs to be more precisely understood. We conducted three different cytogenetic assays to elucidate the biological effects of exposure to mixed pesticides in 20 Costa Rica farmers (all nonsmokers) compared with 20 matched controls. The farmers were also exposed to dibromochloropropane during the early employment years, and most of them experienced sterility/fertility problems. Our data show that the farmers had consistently higher frequencies of chromosome aberrations, as determined by the standard chromosome aberration assay, and significantly abnormal DNA repair responses (p < 0.05), as determined by the challenge assay, but no statistically significant differences in the tandem-probe fluorescence in situ hybridization (FISH) assay (p > 0.05). Genotype analysis indicates that farmers with certain
Letter From the Chairman of the Board to Members of the House of Delegates
Authors: Wesley W. Hall
Journal: JAMA (1966)

On June 29, 1966, Resolution 104 was adopted by the House of Delegates of the American Medical Association at the annual convention in Chicago. Subsequently, and after due deliberation, the Board of Trustees voted unanimously (1) that this resolution should not be implemented by the AMA, and (2) that constituent and component medical societies be advised, likewise, to refrain from implementing Resolution 104.  This letter is intended to inform you of the sequence of events and the reasons for the unusual action taken by the Board of Trustees.  The action of the Board of Trustees was taken pursuant to article VIII of the AMA Constitution, section 163a16 of the Illinois General Not-For-Profit Corporation Act, and the following statement of policy adopted by the House of Delegates in June, 1955, at Atlantic City, NJ:  It is the understanding of the Board of Trustees that prior to any action on the implementation
Liver and bile duct pathology followingCryptosporidium parvum infection of immunodeficient mice
Authors: Janet Stephens, Mary Cosyns, Michelle Jones, Anthony Hayward
Journal: Hepatology (1999)

Patients with acquired immune deficiency syndrome (AIDS) and boys with mutations of the CD154 gene (causing congenital X-linked immunodeficiency with hyper-IgM [XHIM]) are susceptible to chronic infections of the biliary tract with Cryptosporidium parvum (CP) that may lead to biliary sclerosis and ultimately to cholangiocarcinoma. To determine whether the CP infection and the consequent immune response contribute independently to this morbidity, we infected mice with severe combined immunodeficiency (SCID) or with disrupted genes for CD154, CD40, or interferon gamma (IFN-γ) with CP. Even when CP infection persisted for 16 weeks, the SCID mice developed only mild triaditis, without apoptosis of biliary epithelial cells (BEC). Fifty percent of the CD154 knockout mice developed lobular hepatitis with acute and chronic triaditis. The CD40 knockout mice developed marked triaditis, and the IFN-γ knockouts either succumbed to enteritis or survived to develop marked triaditis, portal fibrosis, biliary sclerosis, necrosis with dilation of duct-like structures within the porta hepatis, and dysplastic changes. CP-infected SCID mice reconstituted with T cells from IFN-γ knockout donors either developed severe enteritis or survived to develop triaditis, cholangitis, lobular hepatitis with periductular sclerosis, and scarring. Mice with disruptions of both the CD40 and IFN-γ genes remained infected by CP and developed bile duct and liver disease, but not enteritis. Our results suggest that T-cell cytokines are required for the inflammatory and sclerosing responses to CP infection in immunodeficient animals. The response of immunodeficient mice to CP infection may model at least the initial steps toward the development of sclerosing cholangitis or bile duct cancers in XHIM patients.