tbuckley/cabot-search huggingface dataset:
The platelet count in EDTA‐anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories
Authors: Gian Marco Podda, Mariateresa Pugliano, Eti Alessandra Femia, Anna Maria Mezzasoma, Paolo Gresele, Giovanni Carpani, Marco Cattaneo
Journal: American Journal of Hematology (2012)

Spuriously low platelet counts (PCs) can be observed in normal blood samples anticoagulated with ethylenediamine tetra-acetic acid (EDTA)and, much less frequently, with citrate-tris-pyridossalphosphate (CPT),due to time-dependent in vitro platelet agglutination. Accuracy in PC determination is essential as PC is one of the parameters that usually guides treatment for thrombocytopenic patients. PCs of 93 thrombocy to penic patients were measured in EDTA- or CPT-anticoagulated blood samples immediately after sampling (t0) and 90 min (t90) after storage at room temperature. The presence of platelet agglutinates in blood samples was determined by examining blood smears using optical microscopy.PCs decreased at t90 with both anticoagulants. Platelet agglutinates were present at t90 in 27% of EDTA-samples vs. 2% of CPT-samples with decreased PCs (P < 0.001). Based on PCs in EDTA-samples, 15 patients (16%) shifted from a lower bleeding risk at t0 to a higher bleeding risk category at t90 (P 5 0.019), compared to 5 (5%) patients, based on PCs in CPT-samples. Therefore, time-dependent in vitro platelet agglutination in EDTA-blood samples may cause underestimation of PCs in thrombocytopenic patients, possibly leading to improper management.
NF-κB determines localization and features of cell death in epidermis
Authors: Cornelia S. Seitz, Rachel A. Freiberg, Kaede Hinata, Paul A. Khavari
Journal: Journal of Clinical Investigation (2000)

Specialized forms of physiologic cell death lacking certain characteristic morphologic features of apoptosis occur in terminally differentiating tissues, such as in the outer cell layers of epidermis. In these cell layers, NF-κB translocates from the cytoplasm to the nucleus and induces target gene expression. In light of its potent role in regulating apoptotic cell death in other tissues, NF-κB activation in these cells suggests that this transcription factor regulates cell death during terminal differentiation. Here, we show that NF-κB protects normal epithelial cells from apoptosis induced by both TNFα and Fas, whereas NF-κB blockade enhances susceptibility to death via both pathways. Expression of IκBαM under control of keratin promoter in transgenic mice caused a blockade of NF-κB function in the epidermis and provoked premature spontaneous cell death with apoptotic features. In normal tissue, expression of the known NF-κB–regulated antiapoptotic factors, TRAF1, TRAF2, c-IAP1, and c-IAP2, is most pronounced in outer epidermis. In transgenic mice, NF-κB blockade suppressed this expression, whereas NF-κB activation augmented it, consistent with regulation of cell death by these NF-κB effector proteins. These data identify a new role for NF-κB in preventing premature apoptosis in cells committed to undergoing physiologic cell death and indicate that, in stratified epithelium, such cell death normally proceeds via a distinct pathway that is resistant to NF-κB and its antiapoptotic target effector genes.J. Clin. Invest.105:253–260 (2000).
Over-the-Counter Ibuprofen and Acute Renal Failure
Authors: ALVIN H. MOSS
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 August 1986Over-the-Counter Ibuprofen and Acute Renal FailureALVIN H. MOSS, M.D., RILEY ROGER, M.D., ANTHONY MURGO, M.D., LEE ANN SKAFF, M.D.ALVIN H. MOSS, M.D.Search for more papers by this author, RILEY ROGER, M.D.Search for more papers by this author, ANTHONY MURGO, M.D.Search for more papers by this author, LEE ANN SKAFF, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-105-2-303_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: The availability of ibuprofen (Advil Whitehall Laboratories, New York, New York; and Nuprin, Bristol-Myers Products, New York, New York) as an over-the-counter medication has caused concern because of its many nephrotoxic effects (1). We call attention to the combined effects of volume depletion from influenza and ingestion of aspirin and ibuprofen in inducing acute renal failure.A previously healthy 43-year-old man developed symptoms of influenza (nausea, vomiting, fever, malaise, and myalgias) and took Advil, 200 mg three times a day for 2 days, at the recommendation of his pharmacist after aspirin had failed to alleviate this myalgias....References1. HENRICH W, BENNETT W, and BRATER D. Statement on the release of ibuprofen as an over-the-counter medicine. Am J Kidney Dis. 1985;6:4-5. CrossrefMedlineGoogle Scholar2. MUTHER R and BENNETT W. Aspirin-induced depression of glomerular filtration rate in normal humans: role of sodium balance. Ann Intern Med. 1981;94:317-21. LinkGoogle Scholar3. CLIVE D and STOFF J. Renal syndromes associated with nonsteroidal anti-inflammatory drugs. N Engl J Med. 1984;310:563-72. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ALVIN H. MOSS, M.D.; RILEY ROGER, M.D.; ANTHONY MURGO, M.D.; LEE ANN SKAFF, M.D.Affiliations: West Virginia University School of Medicine Morgantown, WV 26506-6302 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIbuprofenKetoprofenAdverse Drug Reactions Attributed to IbuprofenAtteintes rénales graves au cours d’un traitement par anti-inflammatoires non stéroïdiens arylcarboxyliques : bilan d’une enquête nationale de pharmacovigilanceClinical Pharmacology and Use of Nonsteroidal Anti-Inflammatory DrugsDrugs and the KidneySouthwestern Internal Medicine Conference: Analgesic NephropathyAnti-inflammatory analgesics and drugs used in rheumatoid arthritis and gout 1 August 1986Volume 105, Issue 2 Page: 303-303 Keywords Acute renal failure Aspirin Fevers Ibuprofen Ingestion Myalgia Nausea Pharmacists Vomiting ePublished: 1 December 2008 Issue Published: 1 August 1986 PDF downloadLoading ...
Desiderius Erasmus
Authors: C. D. O'Malley
Journal: JAMA (1971)

It may or may not be true that the pen is mightier than the sword, but no one ever exemplified that maxim better than the Dutch humanist Desiderius Erasmus, born of illegitimate parentage around 1466. As a youth he was immured in a cloister, presumably dead to the outer world. Nevertheless, through intelligence, avid desire for learning, and a kind of discreet beggary from the wealthy and powerful to support his studies, Erasmus was to attain a mastery of Latin style which made him the greatest writer and publicist of his age. His correspondence, which fills 11 closely printed volumes, includes letters to and from emperors, kings, and popes, all of them wanting his services as minister, bishop, or cardinal. Erasmus was not precocious. Not until he was more than 40 years of age did his writings begin to make their mark upon the world; and it was from about
Abstract 2447: Activation of Chk1 critical for Piperine induced cell cycle arrest and apoptosis in melanoma cells.
Authors: Neel M. Fofaria, Sanjay K. Srivastava
Journal: Cancer Research (2013)

Abstract The National Cancer Institute estimates that about 76,250 new cases of melanomas will be diagnosed in 2012 in the United States leading to at least 9810 related deaths. Therefore, novel strategies to control and treat melanoma are of prime importance. In this study, we determined the cytotoxic effects of Piperine, a major constituent of black (Piper nigrum Linn) and long pepper (Piper longum Linn), in melanoma cell lines. Piperine treatment inhibited the growth of SKMEL-28 and B16-F0 cells in a dose and time-dependent manner. The growth inhibitory effects of piperine were mediated by cell cycle arrest of both the cell lines in G1 phase. The G1 arrest by piperine was correlated with the down-regulation of cyclin D1 and induction of p21. The growth arrest was associated with DNA damage as indicated by phosphorylation of H2A.X at Ser139, activation of ataxia telangiectasia and Rad3-related protein (ATR) and checkpoint kinase 1 (Chk1). The G1 arrest by piperine was also associated with the down-regulation of E2F1 and decreased phosphorylation of retinoblastoma protein (Rb), hence indicating the inhibition of the dynamic transcription complex. In addition, apoptosis induced by piperine was associated with down-regulation of XIAP and Bid (uncleaved) and cleavage of Caspase-3 and PARP. Pretreatment of SK-MEL-28 with AZD 7762, a Chk1 inhibitor not only abrogated the activation of Chk1 but also piperine mediated G1 arrest. Silencing of Chk1 in SK-MEL28 cells with Chk1 siRNA completely protected the cells from G1 arrest induced by piperine treatment showing the involvement of Chk1. Through immunofluorescence of Phospho Chk1 (Ser 256), we found significant activation of Chk1 in the cells that were treated with piperine hence, establishing the role of Chk1 activation. Furthermore, our results showed that piperine treatment caused ROS generation in melanoma cells. Blocking ROS generation by Tiron pre-treatment prevented the cells from piperine mediated cell cycle arrest. Moreover, western-blotting results showed that Tiron pre treatment prevented the activation of Chk1 hence, confirming the role played by Chk1 in piperine mediated cell cycle arrest. Taken together, our results demonstrate that piperine induced G1 phase cell cycle arrest by generating ROS and inducing DNA damage with activation of Chk1 being a critical event. [Supported in part by R01 grants CA106953 and CA129038 (to S.K.S) awarded by the National Cancer Institute]. Citation Format: Neel M. Fofaria, Sanjay K. Srivastava. Activation of Chk1 critical for Piperine induced cell cycle arrest and apoptosis in melanoma cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2447. doi:10.1158/1538-7445.AM2013-2447
Abstract 1267: Metabolic sensor O-GlcNAc Transferase is a novel regulator of prostate cancer invasion and angiogenesis via regulation of FoxM1
Authors: Thomas P. Lynch, S. RaElle Jackson, Kristina S. Shahriari, Christina M. Ferrer, Michael Lazarus, Suzzane Walker, Keith Vosseller, Mauricio J. Reginato
Journal: Cancer Research (2011)

Abstract Cancer cells universally increase glucose and glutamine consumption, leading to the altered metabolic state known as the Warburg effect. One metabolic pathway highly dependent on glucose and glutamine is the Hexosamine Biosynthetic Pathway (HBP). Increased flux through the HBP leads to increases in the post-translational addition of O-linked-β-N-acetylglucosamine (O-GlcNAc) on a diverse population of nuclear and cytosolic proteins. A number of these target proteins are implicated in cancer, yet the role of O-GlcNAc modifications in cancer remains poorly defined. Here, we show that OGT is overexpressed in prostate cancer tissue compared to normal prostate epithelium and, that OGT protein and O-GlcNAc levels are elevated in prostate carcinoma cell lines compared to non-transformed prostate cells. Decreasing O-GlcNAc levels using OGT-targeted RNAi in the metastatic prostate cancer cell line PC3-ML inhibited growth in three-dimensional (3D) culture, as well as decreased colony formation in soft agar assays. Furthermore, decreasing O-GlcNAc levels was also associated with cell cycle arrest at G1 and increased expression of the CDK inhibitors p27 and p21. However, reducing O-GlcNAc levels in the non-tumorigenic prostate epithelial cell line RWPE-1 had minimal effects on growth in 3D culture. In addition to growth inhibition, reducing O-GlcNAcation in PC3-ML cells was associated with reduced expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and vascular endothelial growth factor (VEGF), resulting in the inhibition of invasion and angiogenesis. OGT regulation of invasion and angiogenesis was dependent upon regulation of the oncogenic transcription factor FoxM1, as reducing OGT expression led to increased FoxM1 proteasomal degradation. Moreover, overexpression of a FoxM1 degradation-resistant mutant abrogated OGT RNAi inhibition of invasion, MMP levels, as well as angiogenesis and VEGF expression. Finally, the use of novel second-generation small molecule inhibitor of OGT led to the similar reduction in growth, invasion and inhibition of MMPs and VEGF levels. Current experiments are underway to test whether targeting OGT blocks prostate cancer metastasis. Altogether, these data suggest that as prostate cancer cells alter glucose and glutamine levels, O-GlcNAcation serves as nutrient sensitive modification contributing to oncogenesis and suggest that OGT is positioned as a novel target for therapeutic intervention for the treatment of human prostate cancer. 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 1267. doi:10.1158/1538-7445.AM2011-1267
Managed Care — A Look Back and a Look Ahead
Authors: E Ginzberg, M Ostow
Journal: New England Journal of Medicine (1997)

Americans are not inclined to spend much time or effort assessing the past; directing their energies to shaping the future, they believe, will result in much larger benefits. But it can be argued that underinvestment in assessing the past is likely to lead to faulty estimates and erroneous prescriptions for future action.Consider the history of managed care. Initial legislation by Congress in late 1973 to provide federal funding for the expansion of health maintenance organizations (HMOs) and HMO enrollment failed to achieve its goal for a variety of reasons, not least among them the inhibitory effects of excessive administrative . . .
Systemic vasculitis following an unreported rat bite
Authors: R S Tattersall
Journal: Annals of the Rheumatic Diseases (2003)

Association of HLA-DR4/Dw4 with rheumatoid arthritis (RA) is well established, but conflicting data exist on a possible association with the severity of the disease, including its extra-articular manifestations. In order to investigate whether a subgroup of RA is preferentially associated with DR4, HLA typing was performed in two groups of patients with severe extra-articular manifestations (Felty9s syndrome and histologically proved leucocytoclastic vasculitis), patients with severe joint destruction (seropositive and seronegative), a group with only mild joint destruction, and in healthy controls. The frequency of HLA-DR4 was significantly raised in all patient groups compared with that in healthy controls. The two groups with severe extra-articular manifestations, however, both had a DR4 frequency of 92%, which was significantly (p = 0.002) higher than the 62.7% found in the remaining patients. No significant differences were observed between severe or mild joint destruction and seropositivity or seronegativity in the groups without the above-mentioned extra-articular manifestations. From these data we concluded that DR4 is preferentially associated with severe extra-articular disease manifestations of RA. This observation provides an immunogenetic basis for the disease heterogeneity and for the immunological analogy between RA and leprosy.
Tamoxifen Effects on Endothelial Function and Cardiovascular Risk Factors in Men With Advanced Atherosclerosis
Authors: Sarah C. Clarke, Peter M. Schofield, Andrew A. Grace, James C. Metcalfe, Heide L. Kirschenlohr
Journal: Circulation (2001)

Background —Tamoxifen and its analogues act as selective estrogen receptor modulators (SERMs) in women, with estrogen-like activities on some plasma cardiovascular risk factors (eg, lipoproteins). Effects of SERMs on men with coronary artery disease (CAD) have not been reported. Methods and Results —Thirty-one men with angiographically proven CAD were recruited; 16 were treated with tamoxifen (40 mg/d) for 56 days, and 15 were untreated. All the CAD patients were medicated with aspirin and an HMG-CoA reductase inhibitor for ≥6 weeks before entering the study. Ten men with angina-like symptoms but normal coronary arteries by angiography (NCA group) were also treated with tamoxifen. Blood samples were collected at days −7, 0, 7, 14, 21, 28, and 56 of treatment. Endothelium-dependent flow-mediated dilatation (ED-FMD) of the brachial artery was measured by high-resolution ultrasound at 5 visits. Tamoxifen caused an increase in %ED-FMD maximal at 28 days in the CAD group (2.1±0.3% to 7.5±0.7%; P &lt;0.0001) and the NCA group (3.8±0.4% to 7.9±1.0%; P &lt;0.0001), with no significant change in the untreated group. Tamoxifen also caused decreases in several plasma cardiovascular risk factors, including total cholesterol, triglycerides, lipoprotein(a), and fibrinogen. Except for the triglyceride response, these effects were similar to those reported for postmenopausal women treated with tamoxifen. Conclusions —Tamoxifen substantially increased ED-FMD in men with CAD who were taking conventional medication. Together with the effects on risk factors, the data strongly support clinical evaluation of SERMs for the treatment of men with CAD.
MRSA genotypes in Turkey: Persistence over 10 years of a single clone of ST239
Authors: Emine Alp, Corné H.W. Klaassen, Mehmet Doganay, Ulku Altoparlak, Kemalettin Aydin, Aynur Engin, Cigdem Kuzucu, Cuneyt Ozakin, Mehmet Ali Ozinel, Ozge Turhan, Andreas Voss
Journal: Journal of Infection (2009)
Screening for Hypothermia in the Ambulatory Elderly
Authors: Leonard Keilson
Journal: JAMA (1985)

This study investigated the prevalence of low body temperatures in 97 elderly and 20 nonelderly subjects. To the best of our knowledge, no earlier survey has been conducted with a North American population. To ensure comparability with the British National Survey performed in 1973, urine temperatures were collected as a proxy measure of core temperatures. The urine-collecting funnel was modified to minimize cooling artifact introduced by the device. Study subjects were selected from an internal medicine clinic that serves the poor, a federally subsidized housing project, and a subsidized housing project in northernmost Maine. A youthful population (mean age, 32.3 years) was chosen to provide a comparative population to elderly participants (mean age, 73.9 years). Based on the British National Survey, the expected prevalence of low body temperatures (&lt;35.5 °C) was 10%. The present study detected no low body temperatures, and the average urine and mouth temperatures were 0.3 and 0.19 °C warmer, respectively, than those in the British National Survey. Youthful subjects were not significantly different from elderly participants. There appears to be no evidence from this study that low early-morning basal body temperature (&lt;35.5 °C) is a common geriatric occurrence in ambient room temperature. (<i>JAMA</i>1985;254:1781-1784)
Can object affordances impact on human social learning of tool use?
Authors: Pierre O. Jacquet, Alessia Tessari, Ferdinand Binkofski, Anna M. Borghi
Journal: Behavioral and Brain Sciences (2012)

Abstract The author describes “higher” and “uniquely human” sociocognitive skills that he argues as being necessary for tool use. We propose that those skills could be based on simpler detection systems humans could share with other animal tool users. More specifically, we discuss the impact of object affordances on the understanding and the social learning of tool use.
Jaundice due to iprindole
Authors: A. B. Ajdukiewicz, J. Grainger, P. J. Scheuer, S. Sherlock
Journal: Gut (1971)

Twenty-one patients treated for depression with iprindole developed evidence of liver damage: 15 were jaundiced, five had bilirubinuria, and one had pruritus. These complications occurred between four and 21 days after initial exposure to the drug. All patients recovered. Light and electron microscopic findings in liver biopsies of one of these patients were those of cholestasis without inflammation.
Generation of T-Cell Immunity to the HER-2/neu Protein After Active Immunization With HER-2/neu Peptide–Based Vaccines
Authors: Mary L. Disis, Theodore A. Gooley, Kristine Rinn, Donna Davis, Michael Piepkorn, Martin A. Cheever, Keith L. Knutson, Kathy Schiffman
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The HER-2/neu protein is a nonmutated tumor antigen that is overexpressed in a variety of human malignancies, including breast and ovarian cancer. Many tumor antigens, such as MAGE and gp100, are self-proteins; therefore, effective vaccine strategies must circumvent tolerance. We hypothesized that immunizing patients with subdominant peptide epitopes derived from HER-2/neu, using an adjuvant known to recruit professional antigen-presenting cells, granulocyte-macrophage colony-stimulating factor, would result in the generation of T-cell immunity specific for the HER-2/neu protein. PATIENTS AND METHODS: Sixty-four patients with HER-2/neu–overexpressing breast, ovarian, or non–small-cell lung cancers were enrolled. Vaccines were composed of peptides derived from potential T-helper epitopes of the HER-2/neu protein admixed with granulocyte-macrophage colony-stimulating factor and administered intradermally. Peripheral-blood mononuclear cells were evaluated at baseline, before vaccination, and after vaccination for antigen-specific T-cell immunity. Immunologic response data are presented on the 38 subjects who completed six vaccinations. Toxicity data are presented on all 64 patients enrolled. RESULTS: Ninety-two percent of patients developed T-cell immunity to HER-2/neu peptides (stimulation index, 2.1 to 59) and 68% to a HER-2/neu protein domain (stimulation index range, 2 to 31). Epitope spreading was observed in 84% of patients and significantly correlated with the generation of a HER-2/neu protein–specific T-cell immunity (P = .03). At 1-year follow-up, immunity to the HER-2/neu protein persisted in 38% of patients. CONCLUSION: The majority of patients with HER-2/neu–overexpressing cancers can develop immunity to both HER-2/neu peptides and protein. In addition, the generation of protein-specific immunity, after peptide immunization, was associated with epitope spreading, reflecting the initiation of an endogenous immune response. Finally, immunity can persist after active immunizations have ended.