tbuckley/cabot-search huggingface dataset:
Tuberculosis and HIV infection in sub-Saharan Africa
Authors: K. M. De Cock
Journal: JAMA (1992)

To review the epidemiologic, clinical, and pathological characteristics and the public health implications of human immunodeficiency virus (HIV)-associated tuberculosis in sub-Saharan Africa.Published medical literature (English and French) and proceedings of international and African conferences on the acquired immunodeficiency syndrome (AIDS).Selection by the authors of articles most pertinent to HIV infection and tuberculosis in Africa and internationally.Direct reporting of quantitative data (eg, HIV seroprevalence levels) and of qualitative descriptions and conclusions from selected literature.High rates (20% to 67%) of HIV infection in patients with tuberculosis have been reported from East, West, Central, and Southern Africa. An increase in tuberculosis cases has been reported at the same time as the emergence of AIDS in several countries. Autopsies in Abidjan, Ivory Coast (Côte d'Ivoire), have shown tuberculosis as the most frequent opportunistic infection in patients dying of AIDS. Clinical differences in patients with tuberculosis who were HIV-positive and HIV-negative are reviewed, the most important being a greatly increased mortality rate in HIV-associated disease. Access to HIV testing is required for firm diagnosis, for clinical care and counseling, and for public health surveillance.The epidemiology of tuberculosis has been profoundly influenced by the epidemic of HIV infection in sub-Saharan Africa. Greatly increased human and material resources are required for this neglected problem in international health.
Abstract #4459: Down-regulation of cystatin E/M in HPV16 E7 transformed keratinocytes
Authors: Mysore Veena, Hendrick Soh, Grace Kim, Eugene Han, Eri Srivatsan
Journal: Cancer Research (2009)

We have previously identified cystatin E/M as a cervical cancer tumor suppressor gene. Analysis of cervical cancer cell lines and tumors showed cystatin E/M inactivation by epigenetic mechanisms, mutations, and homozygous deletion. To examine if human papilloma virus (HPV) has a role on cystatin E/M, we studied cystatin E/M expression in normal and HPV16 E6, E7, E6 and E7 transformed human keratinocytes. While cystatin E/M expression was observed in all the above mentioned keratinocytes, it\#8217;s expression was reduced in E7 and E6 and E7 expressing keratinocytes. Immunoprecipitation studies showed direct binding of HPV16 E7 and cystatin E/M. Culture supernatants from normal and HPV16 E6 expressing keratinocytes showed growth suppressive effect on HeLa cells. Western blot studies showed presence of cystatin E/M in culture supernatants of normal and HPV16 E6 keratinocytes indicating the growth suppressive effect due to the presence of cystatin E/M protein. However, culture supernatant from HPV16 E7 expressing cells did not inhibit HeLa cell proliferation and cystatin E/M expression in this culture supernatant was very low. These studies confirmed growth suppressive effects of cystatin E/M and indicated a possible mechanism of HPV16 E7 mediated inactivation of cystatin E/M.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4459.
Comparison Of Treatment Results Using High-Dose MTX Plus High-Dose AraC and High-Dose MTX Plus CHOP Regimens For Primary Central Nervous System Lymphoma
Authors: Hitoji Uchiyama, Miki Kiyota, Kazuna Tanba, Eri Kawata, Teruaki Akaogi, Yutaka Kobayashi, Masafumi Taniwaki
Journal: Blood (2013)
Treatment of Meningeal Leucaemia, Meningeal Lymphoma and Carcinomatosis
Authors: R. Somers, Z. D. Goedhart, B. W. Ongerboer de Visser
Journal: Neuro-Oncology (1980)

Before the introduction of the central nervous system (CNS) prophylaxis in acute lymphoblastic leucaemia (ALL) in childhood the incidence of meningeal leucaemia was about 50%. Now it is only 10%, but extension to the meninges might become more frequent in the near future, due to a better patient survival Simultaneous the incidence of meningeal metastases from certain types of malignant lymphoma, such as mediastinal T-cell lymphoma in children and young adults and in hystiocytic lymphoma stage IV, is increasing. Breast cancer, lung cancer and melanoma are the solid tumors which may cause meningeal involvement. The symptoms have been described in the previous paper by Swen. It is the purpose of our paper to discuss the treatment of meningeal metastases and specially the role of the ventriculostomy system (V.S.) of Ommaya (O.S.). Finally the pharmacology and toxicity of MTX will be considered.
Regulation of Human Leukocyte Beta Receptors by Endogenous Catecholamines
Authors: J. Fraser, J. Nadeau, D. Robertson, A. J. J. Wood
Journal: Journal of Clinical Investigation (1981)

High levels of beta receptor agonist have previously been shown to down-regulate beta receptor density on circulating leukocytes in man; however, the factors controlling receptor density under physiological conditions have not previously been defined. To determine whether beta receptor density is normally down-regulated by circulating, physiological levels of catecholamines we have examined the relationship between receptor density and catecholamine levels. Urinary epinephrine and norepinephrine were significantly reciprocally correlated to lymphocyte receptor density. A similar relationship existed between beta receptor density and supine plasma epinephrine, norepinephrine, upright epinephrine, and norepinephrine levels. Change in sodium intake from 10 to 400 meq/d caused a 52% increase in lymphocyte and a 48% increase in polymorphonuclear beta receptor density. The changes in receptor density were accompanied by an increase in the sensitivity to isoproterenol measured as a fall in the dose of isoproterenol required to raise the heart rate by 25 beats per minute. Beta receptor density on both lymphocyte and polymorphonuclear cells was significantly correlated to the cardiac sensitivity to isoproterenol. Propranolol administration resulted in an increase in the density of beta receptors on lymphocyte and polymorphonuclear cells that correlated with the subject's pretreatment catecholamine levels.
Pre-clinical rationales for Trastuzumab use in ovarian carcinoma in situation of minimal residual disease
Authors: Jean Pierre Delord, Cuider Allal, Philippe Rochaix, Eliane Mery, Isabelle Hennebelle, Diane Balin, Etienne Chatelut, Roland Bugat, Pierre Canal
Journal: Cancer Research (2004)

5139   The failure to reduce mortality of epithelial ovarian cancer patients is certainly the result of the early dissemination of cancer cells to secondary intra-abdominal sites. Although the first line chemotherapy leads physicians to observe a state of complete remission in a lot of cases, the relapse is usually observed between 18 and 28 months after diagnosis. This failure is linked to residual disease after induction chemotherapy and surgery. We built up a preclinical model of minimal residual disease of ovarian carcinoma. This model is valuable to determine the antitumor potential of cytostatic drugs. The goal of the study was to evaluate the effect of Trastuzumab (TZ) in terms of interval-free and overall survival in housekeeping mice model of residual ovarian cancer (OVCAR-3). The high activity of topotecan in OVCAR-3 xenograft provided us a model of micrometastatic disease, mimicking the natural history of ovarian cancer. Mice treated with TZ are cured if TZ is started early after induction chemotherapy. We observed cellular and mice peritoneal effects of TZ. The first effect is obtained by the inhibition of proliferation signal transduction (MAP-K pathway) and by the inhibition of AKT expression, leading to apoptosis signal of OVCAR-3 cells. But, these cellular effects do not explain the entire effect of TZ in this model. We observed also morphological changes in mesothelial cells morphology and in mice peritoneal structure. OVCAR-3 cancer cells are able to increase permeability of peritoneal membrane, leading to invasion. On contrary, mice treated by TZ have a normal permeability of peritoneal barrier. These results strongly suggest that TZ modifies paracrine cancer cell function(s), mediated by HER2 kinase pathway inhibition. TZ also restores peritoneal permeability without any effect on cancer cell invasion and/or motility properties.
Man’s best friend: Essential ERBB signaling in canine osteosarcoma as a model for human disease
Authors: Aaron K. Mobley, Pingyu Zhang, Kenneth E. Lee, Yanwen Yang, Dennis P. M. Hughes
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4329 

Background: Osteosarcoma is the most common bone cancer in humans and dogs. In the US each year osteosarcoma is diagnosed in nearly 1,000 people, predominantly adolescents, in whom it is the third most common cancer overall. The largest breeds of dogs, such as Great Dane and Saint Bernard, are at greatest risk, and 10% of these dogs may develop osteosarcoma. Overall, 8,000 to 10,000 new cases of canine osteosarcoma present in the US annually, and the close biologic similarity between human and canine bone cancers allows the spontaneous disease in pet dogs to serve as a model for human osteosarcoma. Further, biologic observations in either species may provide therapeutic benefit to both. We recently have shown that the ERBB family of receptor tyrosine kinases are constitutively phosphorylated in human osteosarcoma, and that inhibition of ERBB signaling with a small molecule inhibitor induces growth arrest and apoptosis in human osteosarcoma cells. We hypothesized that ERBB signaling would be essential to canine osteosarcoma as well. Methods: The use of the pan-ERBB inhibitor CI-1033 (Pfizer Global Research and Development, Ann Arbor, MI) can be used as a probe to assess the importance of ERBB signaling, and to generate preclinical data regarding the potential therapeutic efficacy of ERBB inhibition. Three canine osteosarcoma lines derived from spontaneous tumors (Abrams, Gray and D17) were cultured in the presence or absence of CI-1033. We examined the expression and phosphorylation of EGFR, Her-2, Her-3 and Her-4 using flow cytometry and western blot, and measured the effect of CI-1033 across a range of concentrations (known to be specific for ERBB) on cell growth over four days of continuous exposure. Results: All three canine osteosarcoma cell lines expressed EGFR, Her-2 and Her-4, similar to our previously reported observations in human osteosarcoma. EGFR and Her-2 were constitutively phosphorylated, and treatment with CI-1033 at concentrations of 1 micromolar or higher reduced phosphorylation. ERBB inhibition caused significant growth arrest and apoptosis at concentrations of 3 micromolar or higher. Discussion: ERBB family receptors are constitutively phosphorylated in canine osteosarcoma, and ERBB signaling is essential for growth and survival of canine osteosarcoma, as it is in the human disease. These observations affirm the biologic propriety of using spontaneous osteosarcoma arising in pet dogs as a model for the human disease, and suggests that both teenagers and dogs with osteosarcoma may benefit from small molecule ERBB inhibitors. Clinical trials in dogs may both aid diseased pets and provide preclinical data for human trials.
Visualization of the Vulnerable Plaque
Authors: Rob Krams, Johannes Schaar, Frank Helderman, Caroline Cheng, Babak Mousavi Gourabi, L. C. A. van Damme, D. Segers, Evelyn Regar, Cornelis J. Slager, Pim J. de Feyter, Anton F. W. van der Steen, Patrick W. Serruys
Journal: Cardiovascular Research (2006)

Thrombosis is the main cause of acute coronary syndrome and myocardial infarction (Naghavi et al., 2003). The mechanism underlying thrombus formation is presently under debate, but several pathological conditions have been identified from human postmortem studies that correspond with the presence of thrombus. Of these conditions plaque rupture is the most common, but erosion of the endothelial layer and existence of calcified nodules without the existence of plaque rupture have also been identified. Plaques that have been ruptured have certain features in common (Falk, 1999; Virmani et al., 2002): (i) size of the lipid core (40% of the entire plaque), (ii) thickness of the fibrous cap (less than 65 µm), (iii) presence of inflammatory cells, (iv) amount of remodeling and extent of plaque-free vessel wall. Several terms have been identified focusing either on the pathological aspects ("thin-cap fibroatheroma") or on the possibility to rupture ("rupture-prone plaques") or on the possibility to induce thrombosis ("vulnerable plaque"). As vulnerable plaque is the term encompassing all other terms, therefore this term will be used throughout the chapter.
Is empiric daptomycin effective in reducing mortality in Staphylococcus aureus bacteraemia? A real-life experience
Authors: Matteo Bassetti, Filippo Ansaldi, Daniela De Florentiis, Elda Righi, Federico Pea, Assunta Sartor, Claudio Scarparo, Alessia Carnelutti
Journal: Intensive Care Medicine (2015)
Abstract 1620: Serum Levels of NT-proBNP in Patients with Cardiac Amyloidosis Correlate With Myocardial Mass and Late Gadolinium Enhancement as Assessed by Cardiac Magnetic Resonance Imaging
Authors: Stephanie Lehrke, Henning Steen, Arnt V Kristen, Dirk Lossnitzer, Thomas J Dengler, Hugo A Katus, Evangelos Giannitsis
Journal: Circulation (2007)

Background: Recently the prognostic value of n-terminal brain natriuretic peptide (NT-proBNP) has been recognized in pts with amyloid light chain (AL) or familial transthyretin (ATTR) amyloidosis c...
Impact of Exposure Uncertainty on the Association between Perfluorooctanoate and Preeclampsia in the C8 Health Project Population
Authors: Raghavendhran Avanasi, Hyeong-Moo Shin, Verónica M. Vieira, David A. Savitz, Scott M. Bartell
Journal: Environmental Health Perspectives (2015)

Uncertainty in exposure estimates from models can result in exposure measurement error and can potentially affect the validity of epidemiological studies. We recently used a suite of environmental models and an integrated exposure and pharmacokinetic model to estimate individual perfluorooctanoate (PFOA) serum concentrations and assess the association with preeclampsia from 1990 through 2006 for the C8 Health Project participants. The aims of the current study are to evaluate impact of uncertainty in estimated PFOA drinking-water concentrations on estimated serum concentrations and their reported epidemiological association with preeclampsia. For each individual public water district, we used Monte Carlo simulations to vary the year-by-year PFOA drinking-water concentration by randomly sampling from lognormal distributions for random error in the yearly public water district PFOA concentrations, systematic error specific to each water district, and global systematic error in the release assessment (using the estimated concentrations from the original fate and transport model as medians and a range of 2-, 5-, and 10-fold uncertainty). Uncertainty in PFOA water concentrations could cause major changes in estimated serum PFOA concentrations among participants. However, there is relatively little impact on the resulting epidemiological association in our simulations. The contribution of exposure uncertainty to the total uncertainty (including regression parameter variance) ranged from 5% to 31%, and bias was negligible. We found that correlated exposure uncertainty can substantially change estimated PFOA serum concentrations, but results in only minor impacts on the epidemiological association between PFOA and preeclampsia. Avanasi R, Shin HM, Vieira VM, Savitz DA, Bartell SM. 2016. Impact of exposure uncertainty on the association between perfluorooctanoate and preeclampsia in the C8 Health Project population. Environ Health Perspect 124:126-132; http://dx.doi.org/10.1289/ehp.1409044.
Abstract 3500: Cardiovascular Risk in Women with Non-Specific Chest Pain: Women’s Health Initiative Hormone Trials
Authors: Jennifer G Robinson, Robert Wallace, Marian Limacher, Hong Ren, Barbara Cochrane, Sylvia Wassertheil-Smoller, Judth K Ockene, Judth K Ockene, Patricia Blanchette, Marcia Ko
Journal: Circulation (2007)

Context: Women discharged with a diagnosis of nonspecific chest pain (NSCP) may have an increased risk of subsequent coronary heart disease (CHD) events. The influence of hormone therapy on NSCP is unknown. Methods: The WHI enrolled postmenopausal women aged 50 –79 years. After excluding women with prior cardiovascular disease, 9427 women in the estrogen alone (E-Alone) trial and 15,105 women in the estrogen plus progestin (E + P) trial were included in this analysis. NSCP, defined as having a primary hospital discharge diagnosis of NSCP by ICD-9 code, was reported in 322 E-Alone and 249 E + P women. Risks of subsequent CHD events were estimated using intent-to-treat Cox proportional hazard ratio (HR) models stratified by clinic and adjusted for age and other risk factors. Results: In the fully adjusted models of the combined trials, women with NSCP had a 2-fold greater risk of subsequent nonfatal CHD events including nonfatal myocardial infarction [2.3% vs 1.7%, HR 2.10 (1.11–3.98)], revascularization [3.5% vs 2.6%, HR 1.99 (1.20 –3.30)], and hospitalized angina [3.7% vs 2.3%, HR 2.39 (1.46 –3.92)]. Hormone therapy did not have a significant effect on either the incidence of NSCP hospitalizations [HRs (95% CIs): E-Alone 1.04 (0.81–1.32); E + P 0.78 (0.59 –1.02)] or on the risk of a subsequent CHD event over 7.1 or 5.6 years of follow-up, respectively. Conclusion: A NSCP hospitalization doubles the risk of a subsequent CHD event in postmenopausal women over the next 5 to 7 years. Further research is needed to identify appropriate diagnosis and treatment strategies for women with NSCP.
Impact of MGMT silencing in patients harboring recurrent glioblastoma multiforme treated with surgery and BCNU chemotherapy wafers implantation
Authors: P. Metellus, I. Nanni, B. Coulibaly, F. Fina, N. Eudes, D. Figarella-Branger, O. L. Chinot
Journal: Journal of Clinical Oncology (2008)

11094 Background: The 06-methylguanine DNA methyltransferase (MGMT) is a key enzyme in the DNA repair process after alkylating agent action. Epigenetic silencing of the MGMT gene by promoter methylation has been associated with longer survival in patients with glioblastoma multiforme (GBM) who received alkylating agents. Methods: A retrospective analyze of 23 consecutives patients harboring recurrent GBM treated by surgery with Gliadel wafers implantation was conducted. We tested the relationship between MGMT silencing in the tumor (initial and recurrence) and survival taking in account the others recognized prognostic factors (age, Karnofski index and extent of surgery). MGMT status was determined by four techniques: methylation-specific polymerase-chain-reaction (MSP), immunohistochemistry (IHC), real-time Quantitative RT-PCR (QRT-PCR) and a high-throughput quantitative methylation assay (MethyLight). Results: In all patients, median overall survival (OS) was 24.2 months. Median progression-free survival (PFS) and OS after recurrence were 5.6 and 9 months respectively. PFS rate after recurrence at 6 months was 26.1%. On multivariate analysis, only MGMT status at recurrence determined by MSP (p=0.004) and MethyLight (p=0.0012), and age (p=0.04) were correlated with a better PFS. On multivariate analysis, only MGMT status at recurrence determined by MSP (p=0.046) and MethyLight (p=0.019) were associated with a better OS. On multivariate analysis only MGMT status at initial presentation determined by MSP (p=0.03) and MethyLight (p=0.0049) were correlated with a better PFS after recurrence. Conclusions: MGMT status, determined by MSP and MethyLight techniques, allows prediction of the response to Gliadel wafers implantation in recurrent GBM. No significant financial relationships to disclose.
Increase of the number of vancomycin resistant enterococci (VRE) isolated in Helsinki, Finland
Authors: J Vuopio-Varkila, J Suppola, N Klinger, E Tarkka, E Kolho
Journal: Eurosurveillance (1997)

The emergence of hospital acquired infections with bacteria resistant to antimicrobials such as vancomycin resistant enterococci (VRE) has become a worldwide concern. In hospitals in the United States, VRE have spread quickly and currently account for eve
Abstract 5192: G Protein-coupled Receptor Kinase-5 Attenuates Atherosclerosis by Reducing PDGF-induced Smooth Muscle Cell Proliferation and Migration
Authors: Jiao-Hui Wu, Xinjiang Cai, Lisheng Zhang, Karsten Peppel, Krishn Sharma, David A Zidar, Leigh Brian, Neil J Freedman
Journal: Circulation (2009)

G protein-coupled receptor kinase-5 (GRK5) is a Ser/Thr kinase that up-regulates in atherosclerotic arteries; it phosphorylates and desensitizes many receptors important to atherogenesis, including heptahelical receptors and the platelet-derived growth factor receptor- β (PDGFR β ). We therefore tested the hypothesis that GRK5 reduces atherogenesis, by comparing atherosclerosis in male C57BL/6-congenic apoe −/− / grk5 −/− and apoe −/− mice, fed a Western diet for 12 wk from age 5 wk, with equivalent serum cholesterols and blood pressures. Aortic atherosclerosis (en face) was 50% greater in grk5 −/− (n=20) than in grk5 +/+ (n=18) mice: Sudanophilic lesions covered 10.6±0.8% versus 7.0±0.5% of aortic area, respectively ( p &lt;0.001). To test whether this difference could result from GRK5-mediated regulation of arterial smooth muscle cells (SMCs) in vivo, we denuded the common carotid endothelium with a 0.36-mm wire in 25-wk-old male B6-congenic WT and grk5 KO mice, using a procedure we previously showed (by bone marrow transplant) produces neointimal hyperplasia comprising SMCs derived only from arterial media. Before injury, GRK5 KO and WT carotids had identical luminal and medial areas. However, 4 wk after injury, neointimal area was 350% greater in GRK5 KO (0.06±0.01 mm 2 ) than in WT mice (0.017±0.007 mm 2 ) (n=5/group, p&lt;0.02), but medial areas were equivalent. Two wk after injury, medial SMCs showed 80±20% greater PDGFR β activation per cell in GRK5 KO than in WT arteries (n=3/group, p&lt;0.02), judged by quantitative immunofluorescence microscopy for PDGFR β -phospho-Tyr 1021 ; total PDGFR β levels were equivalent in KO and WT arteries. In vitro, SMC proliferation evoked by PDGF or 2.5% FBS was greater in GRK5 KO than in WT SMCs (3 lines/genotype, p&lt;0.05), by 80±30% and 33±8%, respectively (assessed by SMC counting). Migration (in modified Boyden chambers) was also greater in GRK5 KO than WT SMCs, by 70±20%, 160±20% and 200±30%, respectively, in response to PDGF, 10% FBS, and activated macrophages (p&lt;0.05), despite equivalent GRK5 KO and WT CD4 + lymphocyte migration. We conclude that GRK5 attenuates atherosclerosis, at least in part, by reducing SMC migration and proliferation evoked through the PDGFR β , and perhaps other SMC receptors activated by macrophages.