tbuckley/cabot-search huggingface dataset:
Bile salt-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide as a hepatoprotective agent
Authors: Walee Chamulitrat, Jürgen Burhenne, Tobias Rehlen, Anita Pathil, Wolfgang Stremmel
Journal: Hepatology (2009)

A decrease of hepatocellular phosphatidylcholine (PC) is associated with hepatic injury, e.g., in nonalcoholic steatohepatitis (NASH). Therefore, we evaluated the hepatoprotective effect of a PC-precursor lipid specifically targeted to the liver. We synthesized the bile acid-phospholipid conjugate ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE), which was designed to target PC to hepatocytes by way of bile-acid transport systems. We synthesized a fluorescently labeled analogue UDCA-6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl PE (UDCA-NBDPE) for uptake and metabolism studies. Unexpectedly, the majority of UDCA-NBDPE was still intact and not hydrolyzed efficiently in HepG2 cells. For targeting in vivo, NBD fluorescence from UDCA-NBDPE-injected mice was recovered in the liver the most, whereas injection of NBDPE alone resulted in an even distribution in liver, kidneys, and intestine. Cytoprotection by UDCA-LPE was tested in starvation and tumor necrosis factor alpha (TNF-α) apoptosis models using HepG2 cells. Only the intact UDCA-LPE was able to persistently stimulate growth after 36 to 120-hour starvation, and significantly inhibited TNF-α-induced apoptosis. In both models, LPC, LPE, UDCA, or UDCA added with LPE exhibited weak to no cytoprotection. UDCA-LPE stabilized mitochondrial membranes by lowering mitochondrial membrane potential. Western blot analyses of phosphorylated Akt and glycogen synthase kinase-3 (GSK-3)α/β revealed that UDCA-LPE activated phosphatidyl inositol 3-kinase (PI3K)/Akt signaling pathways. The PI3K inhibitor LY294002 or Akt small interfering (si)RNA consistently inhibited the proproliferative effects of UDCA-LPE during starvation. The TNF-α death-receptor extrinsic pathway involves caspase 8 activation, which is inhibited by cellular FLICE-inhibitory protein (cFLIP); thus, cFLIP siRNA was employed in our studies. cFLIP siRNA was able to reverse the cytoprotective effects of UDCA-LPE during TNF-α-induced apoptosis, and UDCA-LPE concomitantly upregulated protein expression of cFLIPL. Conclusion: UDCA-LPE, which targeted the liver in vivo, elicited potent biological activities in vitro by stimulating hepatocyte growth and by inhibiting TNF-α-induced apoptosis. Thus, UDCA-LPE may be suitable for evaluation of treatment efficacy in NASH. (HEPATOLOGY 2009.)
A new type of erythrokeratoderma
Authors: M.A.M. van Steensel, M. van Geel, P.M. Steijlen
Journal: British Journal of Dermatology (2005)

Journal Article A new type of erythrokeratoderma Get access M.A.M. Van Steensel, M.A.M. Van Steensel Department of Dermatology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands M.A.M.van Steensel. E‐mail: mvst@sder.azm.nl Search for other works by this author on: Oxford Academic Google Scholar M. Van Geel, M. Van Geel Department of Dermatology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar P.M. Steijlen P.M. Steijlen Department of Dermatology, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, the Netherlands Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 1, 1 January 2005, Pages 155–158, https://doi.org/10.1111/j.1365-2133.2005.06319.x Published: 01 January 2005 Article history Accepted: 09 May 2004 Published: 01 January 2005
Health needs assessment is not required for priority setting
Authors: S. Petrou
Journal: BMJ (1998)

EDITOR —The series of articles on health needs assessment provided insights into how the approach could be used to describe health problems in populations and to identify inequalities in health and access to services.1 The authors of the articles failed to recognise, however, that prioritising healthcare services on the basis of need can lead to inefficient use of resources.

Allocating finite healthcare resources according to the total amount of ill health in the population —whether this is measured by lives …
Balance testing of concussion patients using dual-task interference
Authors: Verle D Valentine, Jason C Dorman, Thayne A Munce, Hannah K Nelson, Shanna L Kindt, B Joel Tjarks, Michael F Bergeron
Journal: British Journal of Sports Medicine (2013)

Objective To compare the diagnostic utility of balance testing (BT) with a dual-task cognitive challenge to concussion symptom scores (SS). Design Observational clinical trial. Setting Concussion clinic, Sioux Falls, SD, USA. Subjects 18 subjects (12–20 years) diagnosed with a concussion, examined within 10 days of injury and seen for ≥4 visits; 26 healthy, age- and gender-matched controls (BT evaluated 2X). Outcome Measures SS and BT from each clinical visit. Postural stability (AMTI force platform) assessed by velocity (V) of movement and 95% ellipse area (EA) during four BT conditions: eyes open (O), eyes open+cognitive challenge (recite the months of the year backwards; OC), eyes closed (C), and eyes closed+cognitive challenge (CC). Results Concussed group: all tests were abnormal at visit one, with progressive improvement of SS over four visits (mean=35.7, 31.4, 18.5, 10.6) and progressive resolution of postural stability (1.0 SD±normative mean). By visit two, V had resolved in all four conditions; however, all four conditions were still abnormal when measured as EA. By visit three, EA for O, OC, and C tasks returned to normal, while the CC task remained abnormal. By visit four, all BT means had returned to normal. Conclusions Improvements in postural stability coincide (though resolve earlier) with reductions in SS. Although more variable, SS and EA were, more sensitive to abnormality than V. Further validation of this novel methodology may help to establish BT as an effective tool in concussion management and research. Competing interests None.
PTEN Loss Promotes rasHa-Mediated Papillomatogenesis via Dual Up-Regulation of AKT Activity and Cell Cycle Deregulation but Malignant Conversion Proceeds via PTEN-Associated Pathways
Authors: Denggao Yao, Claire L. Alexander, Jean A. Quinn, Michael J. Porter, Hong Wu, David A. Greenhalgh
Journal: Cancer Research (2006)

Abstract PTEN tumor suppressor gene failure in rasHa-activated skin carcinogenesis was investigated by mating exon 5 floxed-PTEN (Δ5PTEN) mice to HK1.ras mice that expressed a RU486-inducible cre recombinase (K14.creP). PTEN inactivation in K14.cre/PTENflx/flx keratinocytes resulted in epidermal hyperplasia/hyperkeratosis and novel 12-O-tetradecanoylphorbol-13-acetate (TPA)–promoted papillomas, whereas HK1.ras/K14.cre/PTENflx/flx cohorts displayed a rapid onset of papillomatogenesis due to a synergism of increased AKT activity and extracellular signal-regulated kinase (ERK) elevation. High 5-bromo-4-deoxyuridine labeling in Δ5PTEN papillomas showed that a second promotion mechanism centered on failures in cell cycle control. Elevated cyclin D1 was associated with both HK1.ras/ERK– and Δ5PTEN-mediated AKT signaling, whereas cyclin E2 overexpression seemed dependent on PTEN loss. Spontaneous HK1.ras/Δ5PTEN malignant conversion was rare, whereas TPA promotion resulted in conversion with high frequency. On comparison with all previous HK1.ras carcinomas, such TPA-induced carcinomas expressed atypical retention of keratin K1 and lack of K13, a unique marker profile exhibited by TPA-induced K14.cre/PTENflx/flx papillomas that also lacked endogenous c-rasHa activation. Moreover, in all PTEN-null tumors, levels of rasHa-associated total ERK protein became reduced, whereas phosphorylated ERK and cyclin D1 were lowered in late-stage papillomas returning to elevated levels, alongside increased cyclin E2 expression, in TPA-derived carcinomas. Thus, during early papillomatogenesis, PTEN loss promotes rasHa initiation via elevation of AKT activity and synergistic failures in cyclin regulation. However, in progression, reduced rasHa-associated ERK protein and activity, increased Δ5PTEN-associated cyclin E2 expression, and unique K1/K13 profiles following TPA treatment suggest that PTEN loss, rather than rasHa activation, gives rise to a population of cells with greater malignant potential. (Cancer Res 2006; 66(3): 1302-12)
High-level Coexpression of JAG1 and NOTCH1 Is Observed in Human Breast Cancer and Is Associated with Poor Overall Survival
Authors: Michael Reedijk, Silvia Odorcic, Lynn Chang, Hui Zhang, Naomi Miller, David R. McCready, Gina Lockwood, Sean E. Egan
Journal: Cancer Research (2005)

Aberrant activation of Notch receptors has been shown to cause mammary tumors in mice. We therefore used in situ hybridization to analyze expression of Notch ligands and receptors in human breast cancer. High levels of JAG1 and NOTCH1 were noted in a subset of tumors with poor prognosis pathologic features (P < 0.05). We therefore used tissue microarrays to analyze the expression of these genes in a collection of breast cancers from patients representing a wide spectrum of clinical stages, and from whom associated follow-up survival data was available (n = 184). Patients with tumors expressing high levels of JAG1 or NOTCH1 had a significantly poorer overall survival compared with patients expressing low levels of these genes [5-year survival rate of 42% versus 65% and median survival of 50 versus 83 months, respectively, for JAG1(Hi vs. Lo) (P = 0.01); 49% versus 64% and 53 versus 91 months, respectively, for NOTCH1(Hi vs. Lo) (P = 0.02)]. Moreover, a synergistic effect of high-level JAG1 and high-level NOTCH1 coexpression on overall survival was observed (5-year survival rate of 32% and median survival of 40 months; P = 0.003). These data (a) identify novel prognostic markers for breast cancer, (b) suggest a mechanism whereby Notch is activated in aggressive breast tumors, and (c) may identify a signaling pathway activated in poor prognosis breast cancer which can be therapeutically targeted.
His-Purkinje conduction during retrograde stress.
Authors: M E Josephson, J A Kastor
Journal: Journal of Clinical Investigation (1978)

The pattern of retrograde His-Purkinje conduction was evaluated in 28 patients using ventricular extrastimuli. In each patient progressive prolongations of His-Purkinje conduction (S2H2) which appeared as ventricular extrastimuli were induced at closer coupling intervals (S1S2). There was an inverse linear relationship of S2H2 to S1S2 which was cycle length-dependent: i.e., at any S1S2 interval the resultant S2H2 was less at shorter drive cycle lengths. The degree of S2H2 delay varied widely (from 30 to 340 ms) and was unrelated to the presence of bundle branch block, H-V intervals, or capability of ventriculoatrial conduction. Prolongation of S2H2 was independent of intraventricular (muscle) conduction delay; such delay was usually absent at most, and occasionally all, S1S2 coupling intervals during which S2H2 was lengthening. Furthermore, in two patients both left and right ventricles were activated before the timed depolarization of the His bundle occurred, demonstrating that under the stress of extrastimuli, the impulse conducts through ventricular muscle with less delay than through the His-Purkinje system. We conclude that the His-Purkinje system typically displays slow conduction response to ventricular stress. The site of this conduction delay is probably at the distal "gate".
IgH/TCR rearrangements are common in MLL translocated adult AML and suggest an early T/myeloid or B/myeloid maturation arrest, which correlates with the MLL partner
Authors: C Dupret, V Asnafi, D Leboeuf, C Millien, R Ben Abdelali, C Preudhomme, K Beldjord, E Delabesse, E Macintyre
Journal: Leukemia (2005)
Abstract 5435: The potential of ginseng for cancer chemoprevention
Authors: Chong-Zhi Wang, Tyler D. Calway, Chun-Su Yuan
Journal: Cancer Research (2011)

Abstract The clinical management of cancer invariably involves diverse conventional modalities, including surgery, radiation, and chemotherapy. However, the complexity of human cancer requires some alternative management to improve the therapeutic efficacy of conventional treatment and/or the quality of life of cancer patients. Medicinal botanicals have recently gained more attention for cancer management. Numerous effective anticancer drugs have been developed from botanicals, and identifying new herbal sources to develop ideal chemoprevention remains an essential step in advancing the treatment of colorectal cancer. In this study, potential roles of ginseng herbs, especially American ginseng and notoginseng, in cancer chemoprevention are evaluated. The major pharmacologically active constituents of ginsengs are ginsenosides, which can be mainly classified into protopanaxadiol and protopanaxatriol groups. The recognized active anticancer compounds from American ginseng and notoginseng are ginsenosides Rg3, Rh2, and protopanaxadiol. The structure-activity relationship between their chemical structures and pharmacological activities is discussed. Sugar molecules within a ginsenoside have a high impact on cancer cells. Anticancer activities increase with the decrease of sugar number. In addition, we observed that various steaming temperatures and time treatments of the ginseng herbs can change their ginsenoside profiles and enhance their anticancer activities. This heat treatment process may increase the efficacy of ginseng in cancer chemoprevention. (This work was supported in part by the NIH/NCCAM grants AT003255, AT004418 and AT005362). 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 5435. doi:10.1158/1538-7445.AM2011-5435
Correlation of Erythropoietic Toxicity with the Serum Concentration of Chloramphenicol Metabolites in Patients with Renal or Hepatic Insufficiency.
Authors: L. G. Suhrland
Journal: Annals of Internal Medicine (1963)

s1 April 1963Correlation of Erythropoietic Toxicity with the Serum Concentration of Chloramphenicol Metabolites in Patients with Renal or Hepatic Insufficiency.L. G. Suhrland, M.D. (Associate), A. S. Weisberger, M.D., F.A.C.P.L. G. Suhrland, M.D. (Associate)Search for more papers by this author, A. S. Weisberger, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-58-4-731_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe incidence of erythropoietic toxicity due to chloramphenicol was determined in patients with renal or hepatic insufficiency and correlated with alterations in the serum concentration of chloramphenicol metabolites. Erythropoietic depression was determined on the basis of changes in serum iron, delayed appearance of Fe59 in circulating erythrocytes, and by standard hematologic examinations of peripheral blood and bone marrow.Chloramphenicol was administered orally, 2 g daily, to 16 patients with hepatic insufficiency and to 20 patients with renal disease in chronic uremia. The incidence of erythropoietic depression was determined in these patients and compared with that observed in 15 patients with... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio (CI) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1963Volume 58, Issue 4Page: 731-731KeywordsAttentionBloodBone marrowChloramphenicolMetabolitesRenal diseasesToxicity Issue Published: 1 April 1963 PDF DownloadLoading ...
Depletion of endogenous tumor-associated regulatory T cells improves the efficacy of adoptive cytotoxic T-cell immunotherapy in murine acute myeloid leukemia
Authors: Qing Zhou, Christoph Bucher, Meghan E. Munger, Steven L. Highfill, Jakub Tolar, David H. Munn, Bruce L. Levine, Megan Riddle, Carl H. June, Daniel A. Vallera, Brenda J. Weigel, Bruce R. Blazar
Journal: Blood (2009)
Abstract 3875: Effect of Nutlin and E3 ligase inhibitor on p53 and p21 levels in HDM2 expressing LNCaP cells.
Authors: Saamia Shaikh, Melanie Reddy, Sivanesan Dhandayuthapani, Karthikeyan Alagarsamy, Emily Schmitt, Appu Rathinavelu
Journal: Cancer Research (2013)

Abstract HDM2 is a human homologue of murine double minute 2 protein (MDM2), which is also a negative regulator for p53 mediated tumor suppressor mechanisms. The latter is involved in regulating cell proliferation and induction of apoptosis as a means of controlling tumor growth. HDM2 can directly bind to p53 and neutralize its ability to induce p21 transcription. HDM2 also contains E3 ligase activity that is responsible for p53 ubiquitination and proteosomal degradation. Hence, compounds that inhibit E3 ligase activity of HDM2 are expected to lead to elevated p53 levels via inhibition of ubiquitination-mediated degradation. Similarly, blocking HDM2 by Nutlin was also expected to restore the levels of p53. According to existing literature, up-regulation of p53 should lead to activation of downstream pathways, such as induction of p21 protein. To confirm this hypothesis the prostate cancer cell line (LNCaP) was treated with HDM2-E3 ligase inhibitor and Nutlin for a 24-hour time period. The levels of p53 and p21 proteins were measured by Western Blot analysis and the mRNA levels were measured by RT-PCR amplification. Our preliminary results showed that HDM2-E3 ligase inhibitor increased p53 levels in LNCaP cells. The increase in p53 levels was greater in Nutlin treated samples compared to E3 ligase inhibited treated samples. In addition, we suspect that induction of p53 expression may also activate downstream pathways that will eventually lead to inhibition of cyclin-dependent kinases (CDKs) and phospho-retinoblastoma (pRB) protein mediated cell proliferation. To confirm our hypothesis further studies will be conducted. (The financial support from the Royal Dames of Cancer Research Inc., Ft. Lauderdale, Florida is gratefully acknowledged). Citation Format: Saamia Shaikh, Melanie Reddy, Sivanesan Dhandayuthapani, Karthikeyan Alagarsamy, Emily Schmitt, Appu Rathinavelu. Effect of Nutlin and E3 ligase inhibitor on p53 and p21 levels in HDM2 expressing LNCaP 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 3875. doi:10.1158/1538-7445.AM2013-3875
SCANNING ELECTRON MICROSCOPY OF THE BASAL SURFACE OF THE SEPARATED SUCTION BLISTER TOP
Authors: ALAN BOYDE, ROBIN D. G. PEACHEY, JOHN E. W. WHITE
Journal: British Journal of Dermatology (1971)

Journal Article SCANNING ELECTRON MICROSCOPY OF THE BASAL SURFACE OF THE SEPARATED SUCTION BLISTER TOP Get access ALAN BOYDE, ALAN BOYDE Department of Anatomy, University College London, London, W.C.1, St John's Hospital for Disease of the Skin, Lisle Street, London, W.C.2, and Institute of Dermatology, Homerton Grove, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar ROBIN D. G. PEACHEY, ROBIN D. G. PEACHEY Department of Anatomy, University College London, London, W.C.1, St John's Hospital for Disease of the Skin, Lisle Street, London, W.C.2, and Institute of Dermatology, Homerton Grove, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar JOHN E. W. WHITE JOHN E. W. WHITE Department of Anatomy, University College London, London, W.C.1, St John's Hospital for Disease of the Skin, Lisle Street, London, W.C.2, and Institute of Dermatology, Homerton Grove, London, E.9 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 84, Issue 4, 1 April 1971, Pages 346–352, https://doi.org/10.1111/j.1365-2133.1971.tb14230.x Published: 01 April 1971 Article history Accepted: 11 December 1970 Published: 01 April 1971
Adverse Effects of Amiodarone-Reply
Authors: Koonlawee Nademanee
Journal: JAMA (1982)

In Reply.—  We appreciate the opportunity of responding to Dr Alves and colleagues regarding adverse reactions during amiodarone therapy. The striking difference between their findings and ours merits clarification.  Amiodarone is a compound with unique electrophysiological and pharmacokinetic properties. Its side effects develop slowly and are a function of dose as well as duration of therapy; therefore, they will ultimately develop in every patient given a fixed dose (except the smallest). The fact that the drug elimination half-life is extremely variable (16 to 65 days) in different patients makes the correlation of dose with efficacy or side effects difficult, if not impossible, to determine if duration of therapy and, hence, drug accumulation are not taken into account. 1,2 For this reason, the variations in efficacy and side-effect profile of the drug among different investigators is understandable.  However, we are intrigued and surprised by the 57% incidence of chemical and clinical
Effects of Coronary Artery Reperfusion on Myocardial Infarct Size Calculated from Creatine Kinase
Authors: Stephen F. Vatner, Hank Baig, W. Thomas Manders, Peter R. Maroko
Journal: Journal of Clinical Investigation (1978)

The effects of coronary artery reperfusion at 1 and 3 h after occlusion on infarct size (IS) in the conscious dog were compared with a second group of dogs that were not reperfused (24 h occlusion). Infarct size was calculated from creatine kinase (CK) appearing in blood samples (IS(s)) and myocardial CK depletion (IS(m)), and determined from gross and histological inspection of the pathological tissue (IS(p)). Under both conditions, IS(m) correlated well with IS(p). In dogs with 24-h coronary occlusions, IS(s) correlated well with IS(m) (IS(s) = 14.26 + 1.18 x IS(m), r = 0.92). In reperfused dogs, the relationship remained linear but was altered (IS(s) = 15.33 + 2.07 x IS(m), r = 0.89). The slope was significantly greater, P <0.05, than that observed for dogs that were not reperfused, suggesting that more CK appeared in serum per gram of infarct. Similarly, significantly different relationships were observed in the reperfused and nonreperfused dogs, when IS(s) was compared with IS(p). Moreover, the configuration of the serial blood CK curve was changed significantly by reperfusion. In dogs with a 24-h occlusion, CK rose gradually to a peak at 11.4+/-0.5 h. In dogs reperfused at 3 h, CK rose sharply at 3 h and reached a peak at 6.8+/-0.5 h, significantly earlier (P <0.01) than occurred in dogs reperfused at 1 h, i.e., when the peak occurred at 4.2+/-0.4 h. The rapid appearance of CK in blood after reperfusion at 1 and 3 h suggested a washout phenomena. Thus, reperfusion alters the shape of the serial blood CK curve and results in a different linear relationship between calculated and measured infarct size, resulting in greater recovery of CK in blood per unit of infarcted myocardium.
P1-222: Activity and feasibility of biweekly carboplatin (Cb) plus Gemcitabine (G) as first line treatment in small cell lung cancer (SCLC) with extensive disease (ED)
Authors: Juan L. Marti-Ciriquian, Mireia Gil, Ana Blasco, Dolores Isla Casado, Immaculada Maestu
Journal: Journal of Thoracic Oncology (2007)
Antibodies associated with heparin-induced thrombocytopenia (HIT) inhibit activated protein C generation: new insights into the prothrombotic nature of HIT
Authors: M. Anna Kowalska, Sriram Krishnaswamy, Lubica Rauova, Li Zhai, Vincent Hayes, Karine Amirikian, Jeffrey D. Esko, Daniel W. Bougie, Richard H. Aster, Douglas B. Cines, Mortimer Poncz
Journal: Blood (2011)