tbuckley/cabot-search huggingface dataset:
Toothbrushing, inflammation, and risk of cardiovascular disease: results from Scottish Health Survey
Authors: C. de Oliveira, R. Watt, M. Hamer
Journal: BMJ (2010)

<b>Objective</b> To examine if self reported toothbrushing behaviour is associated with cardiovascular disease and markers of inflammation (C reactive protein) and coagulation (fibrinogen). <b>Design</b> National population based survey. <b>Setting</b> Scottish Health Survey, which draws a nationally representative sample of the general population living in households in Scotland. <b>Participants</b> 11 869 men and women, mean age 50 (SD 11). <b>Main outcome measures</b> Oral hygiene assessed from self reported frequency of toothbrushing. Surveys were linked prospectively to clinical hospital records, and Cox proportional hazards models were used to estimate the risk of cardiovascular disease events or death according to oral hygiene. The association between oral hygiene and inflammatory markers and coagulation was examined in a subsample of participants (n=4830) by using general linear models with adjustments. <b>Results</b> There were a total of 555 cardiovascular disease events over an average of 8.1 (SD 3.4) years of follow-up, of which 170 were fatal. In about 74% (411) of cardiovascular disease events the principal diagnosis was coronary heart disease. Participants who reported poor oral hygiene (never/rarely brushed their teeth) had an increased risk of a cardiovascular disease event (hazard ratio 1.7, 95% confidence interval 1.3 to 2.3; P&lt;0.001) in a fully adjusted model. They also had increased concentrations of both C reactive protein (β 0.04, 0.01 to 0.08) and fibrinogen (0.08, −0.01 to 0.18). <b>Conclusions</b> Poor oral hygiene is associated with higher levels of risk of cardiovascular disease and low grade inflammation, though the causal nature of the association is yet to be determined.
VENTILATORY MECHANICS IN PULMONARY EDEMA IN MAN1
Authors: John Turner Sharp, Geraint T. Griffith, Ivan L. Bunnell, David G. Greene
Journal: Journal of Clinical Investigation (1958)

The mechanics of breathing have recently been investigated in patients with a variety of pulmo- nary abnormalities including pulmonary conges- tion due to heart disease (1-3).The present report describes ventilatory mechanics in eight patients with frank pulmonary edema.The data were calculated from simultaneous oscillographic records of tidal volume, air-flow, and esophageal pressure. CLINICAL MATERIALEight patients were studied while in pulmonary edema, and seven of the eight patients were re- studied following recovery from pulmonary edema.The clinical criteria for the diagnosis of pulmonary edema were as follows: 1) moderate to marked dyspnea at rest, 2) moist rates over at least one- half of both lung fields in the absence of fever or other signs of pulmonary infection, 3) evidence of incapacitating heart disease with previous epi- sodes of pulmonary congestion or edema, 4) roentgenographic changes consistent with those seen in pulmonary edema where chest roentgeno- grams were available.In all cases except Case 7, rales were still present during the recovery study indicating the presence of pulmonary congestion.Three patients had rheumatic valvular heart dis- ease, three had arteriosclerotic heart disease, one had hypertensive cardiovascular disease and the remaining patient had myocardial fibrosis and abscess formation and severe anemia.Only in Case 2 was there evidence for any other lung dis- ease than pulmonary edema and congestion.A brief clinical account of each patient is presented in the Appendix.
Multifunctional Gold Nanostar Conjugates for Tumor Imaging and Combined Photothermal and Chemo-therapy
Authors: Haiyan Chen, Xin Zhang, Shuhang Dai, Yuxiang Ma, Sisi Cui, Samuel Achilefus, Yueqing Gu
Journal: Theranostics (2013)

Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi-functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively.The NIR contrast agent Au-cRGD-MPA was shown to have low cytotoxicity.Using tumor cells and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor-targeting capability mediated by RGD peptide binding to its over-expressed receptor on the tumor cells.The multi-therapeutic analogue, Au-cRGD-DOX, integrates targeting tumor, chemotherapy and photo-thermotherapy into a single system.The synergistic effect of photo-thermal therapy and chemotherapy was demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing mouse models.The viability of MDA-MB-231 cells was only 40 % after incubation with Au-cRGD-DOX and irradiation with NIR light.Both tail vein and intratumoral injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase.These results indicate that the multifunctional nanoconstruct is a promising combined therapeutic agent for tumor-targeting treatment, with the potential to enhance the anti-cancer treatment outcomes.
Methadone Maintenance Treatment for 25,000 Heroin Addicts
Authors: Vincent P. Dole
Journal: JAMA (1971)

Methadone maintenance programs in the United States and Canada are now treating about 9,000 former heroin addicts. The data from these studies amply document the safety of this medication and its efficacy in stopping heroin addiction when it is given under good medical control. Detailed statistics have been collected in New York city by our central data office and made available to the independent evaluation committee directed by Dr. Frances Gearing. This committee has recommended continued support and expansion of the maintenance programs. The New York State Narcotics Addiction Control Commission has allocated an increased proportion of its next year's budget to maintenance treatment, and political leaders have called for an immediate expansion of maintenance programs in New York to a caseload of 25,000. It would seem from all this that the only remaining problems of the methadone programs are to live with prosperity, and forget old arguments, now obsolete.
Phase II study of transarterial embolization in european patients with hepatocellular carcinoma: Need for controlled trials
Authors: Jordi Bruix, Antoni Castells, Xavier Montanyà, Xavier Calvet, Concepció Brü, Carmen Ayuso, Lluís Jover, Laura García, Ramon Vilana, Loreto Boix, Joan Rodés
Journal: Hepatology (1994)

Our uncontrolled phase II study was aimed at assessing the efficacy of transarterial embolization in patients with hepatocellular carcinoma and to determine the parameters associated with a favorable response to treatment, improved survival or both. Fifty consecutive patients (25 corresponding to Okuda's stage I and 25 to stage II) with hepatocellular carcinoma (41 being multinodular or massive) were included. Transarterial embolization induced a self limited postembolization syndrome that was well tolerated. Nevertheless, three patients died shortly after the procedure because of tumor progression (two cases) or progressive liver failure. A favorable response (extensive necrosis with reduction of tumor area greater than 50%) was achieved in 81% of the cases, and this result was independently (p < 0.05) related to a preserved performance status and to a lower alpha-fetoprotein concentration. The survival of the patients at 1 and 2 yr was 65% and 38%, respectively, better than the expected survival according to a mathematical model obtained from a historical series of untreated cases (42% and 20%, respectively). Cox regression analysis disclosed that both a favorable therapeutic response and a preserved physical condition (reflected by performance status of 0 or 1) were independently associated with better survival (regression coefficient -2.248 and 0.869, respectively). These data indicate that transarterial embolization has a marked antitumoral effect in patients with inoperable hepatocellular carcinoma and that the therapeutic success is associated with improved survival. Nevertheless, because the potential benefit for survival observed in this uncontrolled study appears to be moderate, prospective controlled trials to ascertain the real usefulness of this therapeutic approach are mandatory.
Cardioprotective Effect Afforded by Transient Exposure to Phosphodiesterase III Inhibitors
Authors: Shoji Sanada, Masafumi Kitakaze, Philip J. Papst, Hiroshi Asanuma, Koichi Node, Seiji Takashima, Masanori Asakura, Hisakazu Ogita, Yulin Liao, Yasuhiko Sakata, Akiko Ogai, Tomi Fukushima, Junko Yamada, Yoshiro Shinozaki, Tsunehiko Kuzuya, Hidezo Mori, Naohiro Terada, Masatsugu Hori
Journal: Circulation (2001)

Phosphodiesterase III inhibitors (PDEIII-Is) improve the hemodynamic status of heart failure via inotropic/vasodilatory effects attributable to the increase in intracellular cAMP level. Direct cardioprotection by PDEIII-Is and its underlying mechanisms, however, have not been identified. We tested the infarct size-limiting effect of PDEIII-Is and the roles of cAMP, protein kinase (PK) A, PKC, and mitogen-activated protein kinase (MAPK) families in open-chest dogs. Methods and Results-- Milrinone, olprinone (PDEIII-Is), or dibutyryl-cAMP (db-cAMP) was injected intravenously 30 minutes before 90-minute ischemia, followed by 6 hours of reperfusion. Olprinone was also examined with an intracoronary cotreatment with a PKA inhibitor (H89), a PKC inhibitor (GF109203X), an extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) throughout the preischemic period. Either PDEIII-Is or db-cAMP caused substantial hemodynamic changes, which returned to control levels in 30 minutes. Collateral flow and percent risk area were identical for all groups. Both PDEIII-Is and db-cAMP increased myocardial p38 MAPK activity during the preischemic period, which was blocked by H89, but not by GF109203X. Both PDEIII-Is and db-cAMP reduced infarct size (19.1+/-4.1%, 17.5+/-3.3%, and 20.3+/-4.8%, respectively, versus 36.1+/-6.2% control, P<0.05 each). Furthermore, the effect of olprinone was blunted by either H89 (35.5+/-6.4%) or SB203580 (32.6+/-5.9%), but not by GF109203X or PD98059. H89, GF109203X, PD98059, or SB203580 alone did not influence infarct size.Pretreatment with PDEIII-Is has cardioprotective effects via cAMP-, PKA-, and p38 MAPK-dependent but PKC-independent mechanisms in canine hearts.
Role of virion-associated glycosylphosphatidylinositol-linked proteins CD55 and CD59 in complement resistance of cell line-derived and primary isolates of HIV-1.
Authors: M Saifuddin, C J Parker, M E Peeples, M K Gorny, S Zolla-Pazner, M Ghassemi, I A Rooney, J P Atkinson, G T Spear
Journal: The Journal of Experimental Medicine (1995)

This study investigates whether cell-derived glycosylphosphatidylinositol-linked complement control proteins CD55 and CD59 can be incorporated into HIV-1 virions and contribute to complement resistance. Virus was prepared by transfection of cell lines with pNL4-3, and primary isolates of HIV-1 were derived from patients' PBMCs. Virus was tested for sensitivity to complement-mediated virolysis in the presence of anti-gp160 antibody. Viral preparations from JY33 cells, which lack CD55 and CD59, were highly sensitive to complement. HIV-1 preparations from H9 and U937 cells, which express low levels of CD55 and CD59, had intermediate to high sensitivity while other cell line-derived viruses and primary isolates of HIV-1 were resistant to complement-mediated virolysis. Although the primary isolates were not lysed, they activated complement as measured by binding to a complement receptor positive cell line. While the primary isolates were resistant to lysis in the presence of HIV-specific antibody, antibody to CD59 induced lysis. Likewise, antibody to CD55 and CD59 induced lysis of cell line-derived virus. Western blot analysis of purified virus showed bands corresponding to CD55 and CD59. Phosphatidylinositol-specific phospholipase C treatment of either cell line-derived or primary isolates of HIV-1 increased sensitivity to complement while incubation of sensitive virus with purified CD55 and CD59 increased resistance to complement. These results show that CD55 and CD59 are incorporated into HIV-1 particles and function to protect virions from complement-mediated destruction, and they are the first report of host cell proteins functioning in protection of HIV-1 from immune effector mechanisms.
B<scp>IOLOGIC</scp> M<scp>ECHANISMS OF THE</scp> P<scp>ROTECTIVE</scp> R<scp>OLE OF</scp> L<scp>UTEIN AND</scp> Z<scp>EAXANTHIN IN THE</scp> E<scp>YE</scp>
Authors: Norman I. Krinsky, John T. Landrum, Richard A. Bone
Journal: Annual Review of Nutrition (2003)

The macular region of the primate retina is yellow in color due to the presence of the macular pigment, composed of two dietary xanthophylls, lutein and zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably formed from either lutein or zeaxanthin in the retina. By absorbing blue-light, the macular pigment protects the underlying photoreceptor cell layer from light damage, possibly initiated by the formation of reactive oxygen species during a photosensitized reaction. There is ample epidemiological evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration, an irreversible process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to be protective against the development of age-related macular degeneration, a causative relationship has yet to be experimentally demonstrated.
The Clinical Relevance of Cancer Cell Lines
Authors: J.-P. Gillet, S. Varma, M. M. Gottesman
Journal: JNCI Journal of the National Cancer Institute (2013)

Although advances in genomics during the last decade have opened new avenues for translational research and allowed the direct evaluation of clinical samples, there is still a need for reliable preclinical models to test therapeutic strategies. Human cancer-derived cell lines are the most widely used models to study the biology of cancer and to test hypotheses to improve the efficacy of cancer treatment. Since the development of the first cancer cell line, the clinical relevance of these models has been continuously questioned. Based upon recent studies that have fueled the debate, we review the major events in the development of the in vitro models and the emergence of new technologies that have revealed important issues and limitations concerning human cancer cell lines as models. All cancer cell lines do not have equal value as tumor models. Some have been successful, whereas others have failed. However, the success stories should not obscure the growing body of data that motivates us to develop new in vitro preclinical models that would substantially increase the success rate of new in vitro–assessed cancer treatments.
Jackknife and Bootstrap Tests of the Composition Vector Trees
Authors: Guanghong Zuo, Zhao Xu, Hongjie Yu, Bailin Hao
Journal: Genomics Proteomics & Bioinformatics (2010)

Abstract Composition vector trees (CVTrees) are inferred from whole-genome data by an alignment-free and parameter-free method. The agreement of these trees with the corresponding taxonomy provides an objective justification of the inferred phylogeny. In this work, we show the stability and self-consistency of CVTrees by performing bootstrap and jackknife re-sampling tests adapted to this alignment-free approach. Our ultimate goal is to advocate the viewpoint that time-consuming statistical re-sampling tests can be avoided at all in using this alignment-free approach. Agreement with taxonomy should be taken as a major criterion to estimate prokaryotic phylogenetic trees.
Magnetic resonance imaging for low back pain: indications and limitations
Authors: N J Sheehan
Journal: Annals of the Rheumatic Diseases (2009)

Magnetic resonance imaging (MRI) is the preferred investigation for most spinal diseases and is increasingly requested for people with low back pain (LBP). However, determining the cause of back pain is complicated as it is often multifactorial and anatomical abnormalities are common in the spine and may not necessarily translate into clinical symptoms. Thus, national guidelines discourage the use of MRI in non-specific LBP and recommend reserving it for the investigation of severe or progressive neurological deficits or for those cases in which serious underlying pathology is suspected. It also has an acknowledged role in planning surgical management in cases of radiculopathy and spinal stenosis. This review summarises the indications for MRI in LBP and calls for improved education of patients and health professionals in the limitations of this investigation.
Signal transducer and activator of transcription 3‐mediated CD133 up‐regulation contributes to promotion of hepatocellular carcinoma
Authors: Cheolhee Won, Byung‐Hak Kim, Eun Hee Yi, Kyung‐Ju Choi, Eun‐Kyung Kim, Jong‐Min Jeong, Jae‐Ho Lee, Ja‐June Jang, Jung‐Hwan Yoon, Won‐Il Jeong, In‐Chul Park, Tae Woo Kim, Sun Sik Bae, Valentina M. Factor, Stephanie Ma, Snorri S. Thorgeirsson, Yun‐Han Lee, Sang‐Kyu Ye
Journal: Hepatology (2015)

Enhanced expression of the cancer stem cell (CSC) marker, CD133, is closely associated with a higher rate of tumor formation and poor prognosis in hepatocellular carcinoma (HCC) patients. Despite its clinical significance, the molecular mechanism underlying the deregulation of CD133 during tumor progression remains to be clarified. Here, we report on a novel mechanism by which interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling up-regulates expression of CD133 and promotes HCC progression. STAT3 activated by IL-6 rapidly bound to CD133 promoter and increased protein levels of CD133 in HCC cells. Reversely, in hypoxic conditions, RNA interference silencing of STAT3 resulted in decrease of CD133 levels, even in the presence of IL-6, with a concomitant decrease of hypoxia-inducible factor 1 alpha (HIF-1α) expression. Active STAT3 interacted with nuclear factor kappa B (NF-κB) p65 subunit to positively regulate the transcription of HIF-1α providing a mechanistic explanation on how those three oncogenes work together to increase the activity of CD133 in a hypoxic liver microenvironment. Activation of STAT3 and its consequent induction of HIF-1α and CD133 expression were not observed in Toll-like receptor 4/IL-6 double-knockout mice. Long-term silencing of CD133 by a lentiviral-based approach inhibited cancer cell-cycle progression and suppressed in vivo tumorigenicity by down-regulating expression of cytokinesis-related genes, such as TACC1, ACF7, and CKAP5. We also found that sorafenib and STAT3 inhibitor nifuroxazide inhibit HCC xenograft formation by blocking activation of STAT3 and expression of CD133 and HIF-1α proteins.
Elastin fragments are pro-inflammatory in the progression of emphysema
Authors: Y Aggarwal
Journal: Thorax (2006)

▴ Houghton AM, Quintero PA, Perkins DL, et al. Elastin fragments drive disease progression in a murine model of emphysema. J Clin Invest2006;116:753–9 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Mice deficient in the macrophage elastase matrix metalloproteinase-12 (MMP-12) do not develop cigarette smoke induced emphysema or show high levels of macrophage accumulation in the lung on exposure to cigarette smoke. However, monocyte migration to the lung in MMP-12 deficient … [1]: {openurl}?query=rft.jtitle%253DJ%2BClin%2BInvest%26rft_id%253Dinfo%253Adoi%252F10.1172%252FJCI25617%26rft_id%253Dinfo%253Apmid%252F16470245%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1172/JCI25617&link_type=DOI [3]: /lookup/external-ref?access_num=16470245&link_type=MED&atom=%2Fthoraxjnl%2F61%2F7%2F567.atom [4]: /lookup/external-ref?access_num=000235854300026&link_type=ISI
Influence of Leptin on Arterial Distensibility
Authors: Atul Singhal, I. Sadaf Farooqi, Tim J. Cole, Stephen O’Rahilly, Mary Fewtrell, Mia Kattenhorn, Alan Lucas, John Deanfield
Journal: Circulation (2002)

Background— The mechanisms by which obesity increases the risk of atherosclerotic cardiovascular disease (CVD) are poorly understood. In experimental models, leptin, a hormone produced by adipose tissue, has been shown adversely to affect vascular health. Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process. Methods and Results— Noninvasive, high-resolution, vascular ultrasound was used to measure brachial artery distensibility in 294 healthy adolescents (aged 13 to 16 years) who had a broad range of body mass indexes. Fat mass was measured by bioelectric impedance analysis; fasting serum leptin concentration by radioimmunoassay; and lipid profile, fasting insulin, glucose, and C-reactive protein concentrations by standard laboratory techniques. Higher leptin concentrations were associated with impaired arterial distensibility (regression coefficient, −1.3% change in arterial distension per 10% increase in leptin; 95% CI, −1.9% to −0.8%; P &lt;0.001). This association was independent of fat mass, blood pressure, and C-reactive protein, fasting insulin, or LDL cholesterol concentrations. Conclusions— Elevation in leptin was associated with impaired vascular function, independent of the metabolic and inflammatory disturbances associated with obesity. Our observations are consistent with data from experimental models and suggest that high leptin concentration is an important mechanism for the adverse influence of body fatness on CVD.
Behavioral Treatment for Substance Abuse in People with Serious and Persistent Mental Illness: A Handbook for Mental Health Professionalsby Alan S. Bellack, Ph.D., A.B.P.P., Melanie Bennett, Ph.D., and Jean Gearon, Ph.D. New York, Brunner-Routledge, 2006, 288 pp., $49.95.
Authors: ROGER D. WEISS
Journal: American Journal of Psychiatry (2007)
The Phosphoinositide-3-Kinase-Akt-mTOR Pathway as a Therapeutic Target in Breast Cancer
Authors: Josh Lauring, Ben Ho Park, Antonio C. Wolff
Journal: Journal of the National Comprehensive Cancer Network (2013)

The phosphoinositide-3-kinase (PI3-kinase)-Akt-mTOR pathway is a central signal transduction pathway that regulates many critical aspects of normal and cancer physiology, including cell proliferation, apoptosis, cell morphology and migration, protein synthesis, and integration of metabolism. In breast cancer, somatic mutations that activate the pathway occur in more than 50% of tumors, underscoring the potentially broad impact of targeting the pathway for therapy. A vast body of preclinical data demonstrates the efficacy of pathway inhibition on tumor growth, and evidence also shows that activation of the pathway occurs in models of acquired resistance to hormonal therapy. This preclinical work led to the investigation of allosteric mTOR inhibitors, everolimus and temsirolimus, in metastatic hormone receptor-positive breast cancer. The recent BOLERO-2 trial comparing everolimus plus exemestane versus placebo plus exemestane in women with resistance to nonsteroidal aromatase inhibitors demonstrated a 6-month improvement in progression-free survival and led to FDA approval of everolimus for this indication in the United States. This landmark trial is the first demonstration of significant clinical benefit using drugs targeting this pathway in breast cancer. Many questions remain about the role of everolimus and other pathway-targeting drugs in clinical development in breast cancer treatment. This article reviews the role of the PI3-kinase-Akt-mTOR pathway in breast cancer biology and the clinical trial evidence available to date.