tbuckley/cabot-search huggingface dataset:
MicroRNA Expression Profiling in Human Ovarian Cancer: <i>miR-214</i> Induces Cell Survival and Cisplatin Resistance by Targeting <i>PTEN</i>
Authors: Hua Yang, William Kong, Lili He, Jian-Jun Zhao, Joshua D. O'Donnell, Jiawang Wang, Robert M. Wenham, Domenico Coppola, Patricia A. Kruk, Santo V. Nicosia, Jin Q. Cheng
Journal: Cancer Research (2008)

Abstract MicroRNAs (miRNA) represent a novel class of genes that function as negative regulators of gene expression. Recently, miRNAs have been implicated in several cancers. However, aberrant miRNA expression and its clinicopathologic significance in human ovarian cancer have not been well documented. Here, we show that several miRNAs are altered in human ovarian cancer, with the most significantly deregulated miRNAs being miR-214, miR-199a*, miR-200a, miR-100, miR-125b, and let-7 cluster. Further, we show the frequent deregulation of miR-214, miR-199a*, miR-200a, and miR-100 in ovarian cancers. Significantly, miR-214 induces cell survival and cisplatin resistance through targeting the 3′-untranslated region (UTR) of the PTEN, which leads to down-regulation of PTEN protein and activation of Akt pathway. Inhibition of Akt using Akt inhibitor, API-2/triciribine, or introduction of PTEN cDNA lacking 3′-UTR largely abrogates miR-214–induced cell survival. These findings indicate that deregulation of miRNAs is a recurrent event in human ovarian cancer and that miR-214 induces cell survival and cisplatin resistance primarily through targeting the PTEN/Akt pathway. [Cancer Res 2008;68(2):425–33]
Hepatic Deficiency in Transcriptional Cofactor TBL1 Promotes Liver Steatosis and Hypertriglyceridemia
Authors: Philipp Kulozik, Allan Jones, Frits Mattijssen, Adam J. Rose, Anja Reimann, Daniela Strzoda, Stefan Kleinsorg, Christina Raupp, Jürgen Kleinschmidt, Karin Müller-Decker, Walter Wahli, Carsten Sticht, Norbert Gretz, Christian von Loeffelholz, Martin Stockmann, Andreas Pfeiffer, Sigrid Stöhr, Geesje M. Dallinga-Thie, Peter P. Nawroth, Mauricio Berriel Diaz, Stephan Herzig
Journal: Cell Metabolism (2011)
Resistance Training Improves Insulin Sensitivity in NIDDM Subjects Without Altering Maximal Oxygen Uptake
Authors: Tomofusa Ishii, Tetsuya Yamakita, Toshihiko Sato, Shiro Tanaka, Satoru Fujii
Journal: Diabetes Care (1998)

To examine the effect of resistance training on insulin sensitivity in nonobese NIDDM patients.Previously sedentary nonobese NIDDM patients were enrolled in a resistance training group (RT; n = 9) or used as sedentary control subjects (SED; n = 8). SED subjects did not perform exercise training because of orthopedic disorders. The training program consisted of two sets of nine exercises with 10-20 repetitions. Subjects trained five times a week for 4-6 weeks. Insulin sensitivity, as assessed by the hyper-insulinemic-euglycemic clamp technique, HbAJc, and body composition, was measured before and after the training period. Maximal oxygen uptake (VO2max) and quadriceps strength were measured in the RT group.The two groups did not differ significantly on any variables before participation in the program. The glucose disposal rate during the hyperinsulinemic-euglycemic clamp increased 48% in the RT group (6.85 +/- 1.86 to 10.12 +/- 3.15 mg.kg-1 lean body mass.min-1; P < 0.05), but remained unchanged in the SED group (5.95 +/- 1.63 to 6.36 +/- 1.61 mg.kg-1 lean body mass.min-1). There was no significant change in body composition in either group. In the RT group, a 16% increase in quadriceps strength (191.1 +/- 45.8 to 216.9 +/- 42.8 Nm; P < 0.05) but no significant change (27.6 +/- 5.0 to 28.6 +/- 6.5 ml.kg-1.min-1) in VO2max was observed.Moderate-intensity, high-volume resistance training improves insulin sensitivity in nonobese NIDDM without altering VO2max.
Impaired glucose homeostasis in transgenic mice expressing the human transient neonatal diabetes mellitus locus, TNDM
Authors: Dan Ma, Julian P.H. Shield, Wendy Dean, Isabelle Leclerc, Claude Knauf, Rémy Burcelin, Guy A. Rutter, Gavin Kelsey
Journal: Journal of Clinical Investigation (2004)

Transient neonatal diabetes mellitus (TNDM) is a rare inherited diabetic syndrome apparent in the first weeks of life and again during early adulthood. The relative contributions of reduced islet β cell number and impaired β cell function to the observed hypoinsulinemia are unclear. The inheritance pattern of this imprinted disorder implicates overexpression of one or both genes within the TNDM locus: ZAC, which encodes a proapoptotic zinc finger protein, and HYMAI, which encodes an untranslated mRNA. To investigate the consequences for pancreatic function, we have developed a high-copy transgenic mouse line, TNDM29, carrying the human TNDM locus. TNDM29 neonates display hyperglycemia, and older adults, impaired glucose tolerance. Neonatal hyperglycemia occurs only on paternal transmission, analogous to paternal dependence of TNDM in humans. Embryonic pancreata of TNDM29 mice showed reductions in expression of endocrine differentiation factors and numbers of insulin-staining structures. By contrast, β cell mass was normal or elevated at all postnatal stages, whereas pancreatic insulin content in neonates and peak serum insulin levels after glucose infusion in adults were reduced. Expression of human ZAC and HYMAI in these transgenic mice thus recapitulates key features of TNDM and implicates impaired development of the endocrine pancreas and β cell function in disease pathogenesis.
Ultrafine Particle Deposition and Clearance in the Healthy and Obstructed Lung
Authors: James S. Brown, Kirby L. Zeman, William D. Bennett
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Section:ChooseTop of pageAbstract <<METHODSRESULTSDISCUSSIONAPPENDIXReferencesCITING ARTICLES
NONOXIDATIVE MODIFICATIONS OF LIPOPROTEINS IN ATHEROGENESIS
Authors: Ira Tabas
Journal: Annual Review of Nutrition (1999)

▪ Abstract The key initiating event in atherosclerosis is the retention of plasma lipoproteins in the subendothelial matrix. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation. There is considerable evidence that many of these biological responses, notably macrophage cholesteryl ester loading (foam cell formation), require subendothelial modification of the retained lipoproteins. Oxidation of lipoproteins is one such modification that likely occurs in vivo and promotes certain atherogenic events, but oxidation cannot explain all aspects of atherogenesis, including certain elements of macrophage foam cell formation. For this reason, there has been renewed interest in other modifications of lipoproteins that may be important in atherogenesis. This review addresses five such lipoprotein modifications, namely aggregation, glycation, immune complex formation, proteoglycan complex formation, and conversion to cholesterol-rich liposomes. The focus is on the evidence that these modifications occur in atherosclerotic lesions and on the potential role of these modified lipoproteins in atherogenesis, with an emphasis on macrophage foam cell formation.
Recommendations for the Use of Antiemetics: Evidence-Based, Clinical Practice Guidelines
Authors: Richard J. Gralla, David Osoba, Mark G. Kris, Peter Kirkbride, Paul J. Hesketh, Lawrence W. Chinnery, Rebecca Clark-Snow, David P. Gill, Susan Groshen, Steven Grunberg, James M. Koeller, Gary R. Morrow, Edith A. Perez, Jeffrey H. Silber, David G. Pfister
Journal: Journal of Clinical Oncology (1999)

Article Tools ASCO SPECIAL ARTICLE Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.9.2971 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10561376 Recommendations for the Use of Antiemetics: Evidence-Based, Clinical Practice Guidelines Richard J. GrallaxRichard J. GrallaSearch for articles by this author , David OsobaxDavid OsobaSearch for articles by this author , Mark G. KrisxMark G. KrisSearch for articles by this author , Peter KirkbridexPeter KirkbrideSearch for articles by this author , Paul J. HeskethxPaul J. HeskethSearch for articles by this author , Lawrence W. ChinneryxLawrence W. ChinnerySearch for articles by this author , Rebecca Clark-SnowxRebecca Clark-SnowSearch for articles by this author , David P. GillxDavid P. GillSearch for articles by this author , Susan GroshenxSusan GroshenSearch for articles by this author , Steven GrunbergxSteven GrunbergSearch for articles by this author , James M. KoellerxJames M. KoellerSearch for articles by this author , Gary R. MorrowxGary R. MorrowSearch for articles by this author , Edith A. PerezxEdith A. PerezSearch for articles by this author , Jeffrey H. SilberxJeffrey H. SilberSearch for articles by this author , David G. PfisterxDavid G. PfisterSearch for articles by this author , Show More From the American Society of Clinical Oncology, Alexandria, VA. https://doi.org/10.1200/JCO.1999.17.9.2971 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
THE EARLY TREATMENT OF FRACTURES
Authors: C. B. Heald
Journal: BMJ (1924)

JOU3i&f143 to be in some danger of letting slip knowledge anid ecpe- rience so hardly won.The Thomas splint with fixed exten- sion from the boot-best obtained by drivinig a long nail or pin thlrough tranisversely between sole and upper, attaching cords or tapes to its ends and tyiing thenm round the end of the splint-should be the standard miiethod for transport.Fractures of Bones of Leg.
Ultrasound Assessment of Inflammation and Renal Tissue Injury With Microbubbles Targeted to P-Selectin
Authors: Jonathan R. Lindner, Ji Song, Jonathan Christiansen, Alexander L. Klibanov, Fang Xu, Klaus Ley
Journal: Circulation (2001)

Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging.Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles.Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.
A clinical tool to determine the necessity of spine radiography in postmenopausal women with osteoporosis presenting with back pain
Authors: C Roux, G Priol, J Fechtenbaum, B Cortet, S Liu-Leage, M Audran
Journal: Annals of the Rheumatic Diseases (2006)

Vertebral fractures are underdiagnosed, although the resulting mortality and morbidity in postmenopausal women with osteoporosis is now recognised. In a population of postmenopausal women with osteoporosis and back pain, symptoms may be related to vertebral fractures or degenerative changes of the spine.To evaluate a population of postmenopausal women presenting with back pain and factors associated with vertebral fractures which were assessable in a clinical setting in order to determine the necessity for spine radiography.Patient questioning and physical examination were carried out and spinal radiographic data collected from 410 postmenopausal women with osteoporosis, with an average age of 74 years, who consulted a rheumatologist for back pain. Of these, 215 (52.4%) patients were diagnosed with at least one vertebral fracture. Logistic regression was used to identify the most relevant clinical features associated with existing vertebral fractures, and to derive a quantitative index of risk.The model included six parameters: age, back pain intensity, height loss, history of low trauma non-vertebral fractures, thoracic localisation of back pain and sudden occurrence of back pain. The scoring system, or the quantitative index, had a maximal score of 16. For a score >or=7, the probability of existing vertebral fracture was >or=43%. The correlation between this quantitative index and the logistic model probability was 0.98, suggesting an excellent and highly significant approximation of the original prediction equation.From six clinical items, an index was built to identify women with osteoporosis and back pain who should have spine radiography. This simple tool may help clinicians to optimise vertebral fracture diagnosis and to make a proper therapeutic decision.
Organic Substrate and Electrolyte Solutions for Oral Rehydration in Diarrhea
Authors: J F Desjeux, S K Nath, J Taminiau
Journal: Annual Review of Nutrition (1994)

The objective of this review is to provide an overview of intermittent fasting regimens, summarize the evidence on the health benefits of intermittent fasting, and discuss physiological mechanisms by which intermittent fasting might lead to improved ...Read More
Impact of Blood Pressure Control and Angiotensin-Converting Enzyme Inhibitor Therapy on New-Onset Microalbuminuria in Type 2 Diabetes
Authors: Piero Ruggenenti, Annalisa Perna, Maria Ganeva, Bogdan Ene-Iordache, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2006)

For assessment of the independent renoprotective effect of BP control and angiotensin-converting enzyme inhibitor (ACEi) therapy, the relationships of baseline BP, BP reduction, and follow-up BP with the incidence of persistent microalbuminuria were evaluated in 1204 hypertensive patients who had type 2 diabetes and normoalbuminuria and were included in the BErgamo Nephrologic Diabetic Complications Trial (BENEDICT) study and were randomly assigned to 3.6 yr of treatment with the ACEi trandolapril (2 mg/d), the nondihydropyridine calcium channel blocker (ndCCB) verapamil SR (240 mg/d), their fixed combination Veratran (trandolapril 2 mg/d plus verapamil SR 180 mg/d), or placebo, plus other antihypertensive medications targeted at systolic/diastolic BP <130/80 mmHg. Follow-up (from month 3 to study end) systolic, diastolic, mean, and pulse BP and their reductions versus baseline--but not baseline BP--independently predicted (P < 0.001) the risk for microalbuminuria. In patients with follow-up BP above medians, ACEi significantly reduced the risk for microalbuminuria to levels that were observed among patients with BP below medians, regardless of ACEi treatment. The same trend was observed among patients with BP reductions below medians. ndCCB therapy did not independently affect microalbuminuria. Patients who were on Veratran had lower BP and less frequently received diuretics, beta blockers, or dihydropyridine dCCB. In hypertensive, normoalbuminuric patients with type 2 diabetes, BP reduction and ACEi therapy both independently may prevent microalbuminuria. ACEi therapy is particularly effective when BP is poorly controlled, whereas ndCCB therapy is ineffective at any level of achieved BP. As compared with trandolapril, Veratran may help with achievement of target BP with less need for concomitant antihypertensive medications.
Involvement of toll-like receptor 2 in pristane-induced lupus
Authors: Vilma Urbonaviciute, Charlotte Starke, Daniela Graef, Markus Mroz, Carsten Kirschning, Georg Schett, Reinhard E Voll
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Autoantibodies against double stranded (ds) DNA and nucleosomes represent a hallmark of systemic lupus erythematosus (SLE).1 However, the mechanisms involved in breaking the immunological tolerance against these poorly immunogenic nuclear components are not fully understood. Recent data indicate that toll-like receptors (TLRs) recognising endogenous ligands may be critically involved in the breaking of peripheral tolerance against nuclear autoantigens.2 Results of this recent studies in non-autoimmune mice provide evidence of a important role of TLR2 in the anti-dsDNA and antihistone IgG autoantibody induction by high mobility group box protein 1-nucleosome complexes derived from apoptotic cells.3 <h3>Objective</h3> Using the pristane-induced mouse model of SLE, the authors further investigated the requirement of TLR2 signalling for induction of lupus-specific autoantibody production and SLE like disease. <h3>Methods</h3> Female C57BL/6 wild-type (WT), TLR2-deficient mice were injected intraperitoneally with a single dose of 500 μl of the hydrocarbon oil pristane. The numbers of plasma cells were determined by flow cytometry. The concentrations of autoantibodies in sera were measured by ELISA. Autoantibody-secreting cells in the kidneys were detected by enzyme-linked immunosorbent spot assay. Renal disease was assessed by semiquantitative measurement of proteinuria in spot urine and quantified over 24 h after collection in metabolic cages as well as by histological analyses. <h3>Results</h3> TLR2<sup>−/−</sup> mice generated reduced numbers of splenic CD138/cytoplasmic κ/λ-L chain<sup>+</sup>/CD25 plasma cells in response to pristane treatment. Anti-dsDNA, antihistone, antinucleosome and some antinuclear antibody IgG responses were delayed and significantly reduced in pristane-treated-TLR2<sup>−/−</sup> mice compared to pristane-treated WT controls. There were markedly lower numbers of total IgG-secreting and anti-dsDNA specific IgG-secreting cells in the kidneys of pristane-treated-TLR2<sup>−/−</sup> mice in comparison to C57BL/6 mice. Importantly, pristane-treated TLR2-deficient mice developed significantly milder renal disease compared to the WT control group. <h3>Conclusion</h3> TLR2 is specifically required for the lupus-specific autoantibody production as well as for development of renal disease in pristane-induced murine lupus model. Specific blocking of TLR2 signalling may therefore be a promising novel strategy for treatment of SLE.
EGFR Promotes Lung Tumorigenesis by Activating miR-7 through a Ras/ERK/Myc Pathway That Targets the Ets2 Transcriptional Repressor ERF
Authors: Yu-Ting Chou, Hua-Heng Lin, Yung-Chang Lien, Yuan-Hung Wang, Chun-Fu Hong, Yu-Rung Kao, Sheng-Chieh Lin, Ying-Che Chang, Shu-Yu Lin, Shu-Jen Chen, Hua-Chien Chen, Shauh-Der Yeh, Cheng-Wen Wu
Journal: Cancer Research (2010)

MicroRNAs (miRNA) mediate distinct gene regulatory pathways triggered by epidermal growth factor receptor (EGFR) activation, which occurs commonly in lung cancers with poor prognosis. In this study, we report the discovery and mechanistic characterization of the miRNA miR-7 as an oncogenic "oncomiR" and its role as a key mediator of EGFR signaling in lung cancer cells. EGFR activation or ectopic expression of Ras as well as c-Myc stimulated miR-7 expression in an extracellular signal-regulated kinase (ERK)-dependent manner, suggesting that EGFR induces miR-7 expression through a Ras/ERK/Myc pathway. In support of this likelihood, c-Myc bound to the miR-7 promoter and enhanced its activity. Ectopic miR-7 promoted cell growth and tumor formation in lung cancer cells, significantly increasing the mortality of nude mice hosts, which were orthotopically implanted with lung cancers. Quantitative proteomic analysis revealed that miR-7 decreased levels of the Ets2 transcriptional repression factor ERF, the coding sequence of which was found to contain a miR-7 complementary sequence. Indeed, ectopic miR-7 inhibited production of ERF messages with a wild-type but not a silently mutated coding sequence, and ectopic miR-7 rescued growth arrest produced by wild-type but not mutated ERF. Together, these results identified that ERF is a direct target of miR-7 in lung cancer. Our findings suggest that miR-7 may act as an important modulator of EGFR-mediated oncogenesis, with potential applications as a novel prognostic biomarker and therapeutic target in lung cancer.
Obesity Is Associated With Larger Arterial Diameters in Caucasian and African-American Young Adults
Authors: Rachel P. Wildman, Vinay Mehta, Trina Thompson, Sarah Brockwell, Kim Sutton-Tyrrell
Journal: Diabetes Care (2004)

Risk factors for larger arterial diameters and enhanced wall thickening have been insufficiently assessed in young adults, an age-group where preventive measures have the greatest impact. Larger vessel diameter and wall thickening may represent underlying vascular remodeling, a dynamic process by which the vascular system attempts to compensate for vascular damage (1). The purpose of the current study was to examine the association between obesity and arterial diameter and wall thickness in healthy Caucasian and African-American young adults. Associations were examined in both the muscular peripheral arteries and the more elastic central arteries.

Measurements were made in 205 participants aged 20–40 years. Exclusion criteria included use of antihypertensive, lipid-lowering, thyroid, blood glucose-lowering, or cardiovascular medications and history of lupus or clinical cardiovascular disease. This study was approved by the University of Pittsburgh’s institutional review board. All participants provided written informed consent before study protocol initiation.

Left brachial artery adventitial diameter was determined during diastole by electronic caliper measurement of the adventitial to adventitial diameter. For common carotid measurements, the left distal common carotid artery near and far walls were imaged, and lines were electronically drawn along a 1-cm segment of the lumen-intima interface and the media-adventitia interface. The mean intima-media thickness (IMT) was averaged over the near and far walls. The lumen diameter (intima-intima distance) was calculated …