tbuckley/cabot-search huggingface dataset:
Abstract C5: Epigenetic regulation of cancer stem cell marker CD133 by transforming growth factor-β
Authors: Hanning You, C. Bart Rountree
Journal: Cancer Research (2009)

Abstract Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. CD133, a trans-membrane glycoprotein, is an important cell surface marker for both stem cells and cancer stem cells in various tissues including liver. CD133 expression was recently linked to poor prognosis in HCC patients. CD133+ liver cancer cells are characterized by resistance to chemotherapy, self-renewal, multi-lineage potential, increased colony formation, and in-vivo cancer initiation at limited dilution. Recent studies demonstrate that CD133 expression is regulated by DNA methylation. In this paper, we explored the role of Transforming Growth Factor β (TGFβ), a multi-functional cytokine that plays a critical role in chronic liver injury, in the regulation of CD133 expression. Materials and Methods: CD133- Huh7 cells were sorted from bulk cultured cells, CD133 expression was analyzed using flow cytometry, immuno-blots and real-time RT-PCR after the cells were treated with TGFβ1, DNA methyltransferase inhibitors and inhibitory Smads. Pyrosequencing was introduced to evaluate CD133 promoter-1 methylation status. Results: TGFβ1 is capable of up-regulating CD133 expression specifically within the Huh7 HCC cell line in a time and dose-dependent manner. Furthermore, forced expression of inhibitory Smads, including Smad6 and Smad7, attenuated TGFβ1-induced CD133 expression. Within CD133-Huh7 cells, TGFβ1 stimulation inhibited the expression of DNA methyltransferases DNMT1 and DNMT3β, which are critical in the maintenance of regional DNA methylation; and global DNMT activity in CD133-Huh7 cells was inhibited by TGFβ1. DNMT3 inhibition by TGFβ1 was partially rescued with overexpression of inhibitory Smads. Lastly, TGFβ1 treatment led to significant demethylation in CD133 promoter-1 in CD133-Huh7 cells. Conclusion: TGFβ1 is able to regulate CD133 expression through inhibition of DNMT1 and DNMT3 expression, and subsequent demethylation of promoter-1. The mechanism by which TGFβ induces CD133 expression is partially dependent on the Smads pathway. Citation Information: Cancer Res 2009;69(23 Suppl):C5.
Common Carotid Intima-Media Thickness and Risk of Stroke and Myocardial Infarction
Authors: Michiel L. Bots, Arno W. Hoes, Peter J. Koudstaal, Albert Hofman, Diederick E. Grobbee
Journal: Circulation (1997)

Background Noninvasive assessment of intima-media thickness (IMT) is widely used in observational studies and trials as an intermediate or proxy end point for cardiovascular disease. However, data showing that IMT predicts cardiovascular disease are limited. We studied whether common carotid IMT is related to future stroke and myocardial infarction. Methods and Results We used a nested case-control approach among 7983 subjects aged ≥55 years participating in the Rotterdam Study. At baseline (March 1990 through July 1993), ultrasound images of the common carotid artery were stored on videotape. Determination of incident myocardial infarction and stroke was predominantly based on hospital discharge records. Analysis (logistic regression) was based on 98 myocardial infarctions and 95 strokes that were registered before December 31, 1994. IMT was measured from videotape for all case subjects and a sample of 1373 subjects who remained free from myocardial infarction and stroke during follow-up. The mean duration of follow-up was 2.7 years. Results were adjusted for age and sex. Stroke risk increased gradually with increasing IMT. The odds ratio for stroke per standard deviation increase (0.163 mm) was 1.41 (95% CI, 1.25 to 1.82). For myocardial infarction, an odds ratio of 1.43 (95% CI, 1.16 to 1.78) was found. When subjects with a previous myocardial infarction or stroke were excluded, odds ratios were 1.57 (95% CI, 1.27 to 1.94) for stroke and 1.51 (95% CI, 1.18 to 1.92) for myocardial infarction. Additional adjustment for several cardiovascular risk factors attenuated these associations: 1.34 (95% CI, 1.08 to 1.67) and 1.25 (95% CI, 0.98 to 1.58), respectively. Conclusions The present study, based on a short follow-up period, provides evidence that an increased common carotid IMT is associated with future cerebrovascular and cardiovascular events.
Antithrombotic activity of TNF-α
Authors: Beatrice Cambien, Wolfgang Bergmeier, Simin Saffaripour, Heather A. Mitchell, Denisa D. Wagner
Journal: Journal of Clinical Investigation (2003)

Basic and clinical observations suggest that thrombosis and inflammation are closely related. Here we addressed the role played by TNF-α in thrombus formation and growth in an in vivo mouse model. Using intravital microscopy, we show that systemic administration of TNF-α at doses found in sepsis transiently inhibits thrombus formation and delays arterial occlusion upon vascular injury. These results were reflected in a prolonged bleeding time. Platelets isolated from the TNF-α–treated mice showed a marked decrease in fibrinogen binding and P-selectin expression as well as reduced platelet aggregation in response to various agonists. In contrast, in vitro treatment of platelets with TNF-α did not affect their function. TNF receptor 1– and 2–deficient mice exhibited normal thrombogenesis in the presence of TNF-α. Additionally, the inhibitory effect of TNF-α was lost either after treatment with NG-monomethyl-L-arginine, an inhibitor of NO production, or in mice deficient for iNOS. These results indicate that under inflammatory conditions, when leukocytes need free passage to transmigrate into tissues, TNF-α decreases platelet activation and inhibits thrombi formation. This effect is not exerted directly on platelets but mediated through the rapid generation of NO in the vessel wall.
Validation of the American Board of Internal Medicine Written Examination
Authors: CHARLES F. SCHUMACHER
Journal: Annals of Internal Medicine (1973)

The validity of the Written Examination of the American Board of Internal Medicine was investigated by comparing the test performance of first- and third-year residents in internal medicine. These criterion groups were matched by graduate training programs and types of internship served. Statistically significant differences in favor of the third-year trainees were found for each section of the test and for the test as a whole, indicating that the examination is a valid measure of achievement at the graduate level. Differences between criterion groups on the various sections of the test suggest that the physician's ability to gather clinical data is relatively well developed when he enters residency training and improves at a slower rate during graduate training than do the knowledge and skills necessary to solve difficult diagnostic problems and to prescribe appropriate treatment for the kinds of illnesses with which the specialist in internal medicine is expected to deal.
The Year of the Child: an objective for rich nations
Authors: I. Smith, D. Morley
Journal: BMJ (1978)

given that of five patients with deteriorating renal function, three were on gentamicin alone and two on gentamicin plus a cephalosporin.Of the three on gentamicin alone they say, "All three patients were also suffering from transplant rejection and toxaemia, and interpretation of these results is therefore difficult."Of the two on gentamicin plus a cephalosporin they say, "Although in both cases rejection was occurring, we could not exclude nephrotoxicity."They do not present any evidence to explain why in the one situation they conclude, "attributable nephrotoxicity not observed," while in the other they conclude, "may have produced nephrotoxicity."Furthermore, in view of the accumulating evidence that gentamicin appears to be potentially more nephrotoxic than some other aminoglycosidesl-3 attention might have been drawn to the fact that, whether or not it was attributable, all five patients who showed deteriorating renal function were actually receiving gentamicin and not one of the other aminoglycosides included in the study.
Campaign to expand access to antiretrovirals faces major obstacles
Authors: Fiona Fleck
Journal: BMJ (2005)

The number of patients receiving lifesaving antiretroviral drugs in poor countries rose to an estimated 700 000 in December 2004 from 440 000 in July, boosted by progress in sub-Saharan Africa, according to the World Health Organization and UNAIDS, the joint United Nations programme on …
Intraventricular early diastolic filling during acute myocardial ischemia, assessment by multigated color m-mode Doppler echocardiography.
Authors: M Stugaard, O A Smiseth, C Risöe, H Ihlen
Journal: Circulation (1993)

BACKGROUND Color M-mode Doppler echocardiography has been suggested as a new noninvasive technique for assessing left ventricular diastolic function. The present study investigated intraventricular filling pattern by color M-mode Doppler in patients during percutaneous transluminal coronary angioplasty (PTCA). In a dog model of myocardial ischemia, the color M-mode flow pattern was related to indices of global and regional myocardial function. METHODS AND RESULTS From color M-mode images, the time difference (TD) between occurrence of peak velocity in the apical region and at the mitral tip was determined in 20 patients and eight anesthetized dogs during coronary occlusions. During PTCA, the timing of peak velocity was progressively delayed from mitral valve to apex. Consistent with this, the dog model showed delayed apical filling during coronary occlusion; TD increased from 18 +/- 4 to 71 +/- 9 milliseconds (P &lt; .01). In the ischemic region, systolic shortening (sonomicrometry) decreased from 20 +/- 3% to -5 +/- 2% (p &lt; .01). The one-third filling fraction decreased from 59 +/- 5% to 31 +/- 6% (P &lt; .01) and correlated with TD (r = .85, P &lt; .01). The time constant of isovolumic relaxation (tau) increased slightly and correlated with TD (r = .81, P &lt; .01). Pacing tachycardia, caval constriction, and volume loading were performed to mimic the ischemia-induced changes in heart rate, stroke volume, and intracavitary filling pressure, respectively. There were no significant changes in TD or tau during these interventions. CONCLUSIONS Color M-mode Doppler echocardiography showed a marked delay of apical peak filling velocity during PTCA. The experimental data suggest that this reflects retarded filling of the ischemic ventricle. Thus, color M-mode Doppler may provide a useful method for assessing diastolic dysfunction.
Regarding "The Boy's Venereal Peril."
Authors: Ferd. C. Valentine.
Journal: JAMA (1903)

New York, July 16, 1903. <i>To the Editor:</i>—Since publication of the above-mentioned article, I have received requests for 2,090 reprints thereof. Pressure of practice renders me unable to reply individually to each one of the gentlemen who wrote me on the subject. I therefore ask the privilege of using your columns to answer all. 1. The kind sentiments which my correspondents convey stimulate me to greater efforts than ever before, so to revise the article that it may represent the best work of which I am capable. I need not tell other busy practitioners that I can not do this within the next few days. I expect, however, to have the reprints ready in about three weeks. 2. A number of those who have favored me, ask for "some" or "several" copies. If they will kindly specify how many they desire I will know how large an order for
Effects of the Sauna
Authors: A. J. Searle
Journal: JAMA (1982)

To the Editor.—  In the letter Effect of Sweating (1981;246:623), MAJ Ward Dean, MC, USA, claims that the loss of 500 g of sweat in a sauna consumes nearly 300 kcal. I would consider this highly doubtful, since extrapolating these figures would suggest that survival in a hot climate, where several liters of sweat may be lost daily, would require an increased caloric intake for this loss compared with the same daily activities in a more temperate zone, and clearly this does not happen.  He also suggests that the regular use of a sauna may be as effective a means of cardiovascular conditioning as regular exercise. Since the improvement in cardiovascular efficiency associated with exercise is due mainly to peripheral (skeletal muscle) rather than myocardial changes, it is difficult to envisage how this can also be achieved by the inactivity of the sauna.
Hemodynamic effects of urotensin II and its specific receptor antagonist palosuran in cirrhotic rats
Authors: Jonel Trebicka, Ludger Leifeld, Martin Hennenberg, Erwin Biecker, Andreas Eckhardt, Nicolas Fischer, Andrea Schulze Pröbsting, Christoph Clemens, Frank Lammert, Tilman Sauerbruch, Jörg Heller
Journal: Hepatology (2008)

In cirrhosis, splanchnic vasodilation contributes to portal hypertension, subsequent renal sodium retention, and formation of ascites. Urotensin II(U-II) is a constrictor of large conductive vessels. Conversely, it relaxes mesenteric vessels, decreases glomerular filtration, and increases renal sodium retention. In patients with cirrhosis, U-II plasma levels are increased. Thus, we investigated hemodynamic and renal effects of U-II and its receptor antagonist, palosuran, in cirrhotic bile duct-ligated rats (BDL). In BDL and sham-operated rats, we studied acute effects of U-II (3 nmol/kg; intravenously) and palosuran (10 mg/kg; intravenously) and effects of oral administration of palosuran (30 mg/kg/day; 3 days) on hemodynamics and renal function. We localized U-II and U-II-receptor (UTR) in livers and portal veins by immunostaining. We determined U-II-plasma levels by enzyme-linked immunosorbent assay (ELISA), and mesenteric nitrite/nitrate-levels by Griess-reaction. RhoA/Rho-kinase and endothelial nitric oxide synthase (eNOS) pathways were determined by western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) in mesenteric arteries. U-II plasma levels, as well as U-II and UTR-receptor expression in livers and portal veins of cirrhotic rats were significantly increased. U-II administration further augmented the increased portal pressure (PP) and decreased mean arterial pressure (MAP), whereas palosuran decreased PP without affecting MAP. The decrease in PP was associated with an increase in splanchnic vascular resistance. In mesenteric vessels, palosuran treatment up-regulated expression of RhoA and Rho-kinase, increased Rho-kinase-activity, and diminished nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling. Moreover, palosuran increased renal blood flow, sodium, and water excretion in BDL rats.In BDL rats, U-II is a mediator of splanchnic vasodilation, portal hypertension and renal sodium retention. The U-II-receptor antagonist palosuran might represent a new therapeutic option in liver cirrhosis with portal hypertension.
CCL5-Mediated Endogenous Antitumor Immunity Elicited by Adoptively Transferred Lymphocytes and Dendritic Cell Depletion
Authors: Yolanda Nesbeth, Uciane Scarlett, Juan Cubillos-Ruiz, Diana Martinez, Xavier Engle, Mary-Jo Turk, Jose R. Conejo-Garcia
Journal: Cancer Research (2009)

Adoptive transfer of antitumor T cells is a promisingly effective therapy for various cancers, but its effect on endogenous antitumor immune mechanisms remains largely unknown. Here, we show that the administration of naive T cells de novo primed for only 7 days against tumor antigens resulted in the durable rejection of otherwise lethal ovarian cancers when coupled with the depletion of tumor-associated immunosuppressive dendritic cells (DC). Therapeutic activity required tumor antigen specificity and perforin expression by the adoptively transferred T cells, but not IFN-gamma production. Importantly, these shortly primed T cells secreted large amounts of CCL5, which was required for their therapeutic benefit. Accordingly, transferred T cells recruited CCR5(+) DCs into the tumor, where they showed distinct immunostimulatory attributes. Activated CCR5(+) host T cells with antitumor activity also accumulated at tumor locations, and endogenous tumor-specific memory T cells remained elevated after the disappearance of transferred lymphocytes. Therefore, persistent, long-lived antitumor immunity was triggered by the administration of ex vivo activated T cells, but was directly mediated by immune cells of host origin. Our data unveil a CCL5-dependent mechanism of awakening endogenous antitumor immunity triggered by ex vivo expanded T cells, which is augmented by tumor-specific targeting of the cancer microenvironment.
Median nail dystrophy associated with isotretinoin therapy
Authors: W.W. Bottomley, W.J. Cunliffe
Journal: British Journal of Dermatology (1992)

Journal Article Median nail dystrophy associated with isotretinoin therapy Get access W.W. Bottomley, W.W. Bottomley Department of Dermatology, The General Infirmary at Leeds, Great George Street, Leeds, U.K. Search for other works by this author on: Oxford Academic Google Scholar W.J. Cunliffe W.J. Cunliffe Department of Dermatology, The General Infirmary at Leeds, Great George Street, Leeds, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 127, Issue 4, 1 October 1992, Pages 447–448, https://doi.org/10.1111/j.1365-2133.1992.tb00472.x Published: 01 October 1992
Urea, Urease, Cyanate and the Sickling of Hemoglobin S.
Authors: Robert M. Nalbandian
Journal: Annals of Internal Medicine (1973)

Meeting Abstracts1 May 1973Urea, Urease, Cyanate and the Sickling of Hemoglobin S.Robert M. Nalbandian, M.D., Bruce M. Nichols, B.S., Noyes L. Avery Jr, M.D., F.A.C.P., COL Frank R. Camp JrRobert M. Nalbandian, M.D.Search for more papers by this author, Bruce M. Nichols, B.S.Search for more papers by this author, Noyes L. Avery Jr, M.D., F.A.C.P.Search for more papers by this author, COL Frank R. Camp JrSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-78-5-823_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptUrea in sugar solutions has been experimentally and clinically effective in the sickle-cell disease because of its demonstrated reversal and blocking actions on sickled erythrocytes. This beneficial effect has been attributed to the formation of cyanate in vivo and subsequent carbamylation of beta S globin chains. By controlled studies in oxygen-free atmospheres we have found that SS cells, protected from sickling by urea-sugar solutions (blood urea nitrogen level of 140 mg/100 ml), were again sickled after the addition of urease, which had no such effect on carbamylated cells.Urea blocks and reverses sickling; urea-protected cells aresickled by urease treatment;... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Robert M. Nalbandian, M.D.; Bruce M. Nichols, B.S.; Noyes L. AveryJr, M.D., F.A.C.P.; COL Frank R. CampJrAffiliations: Detroit, Michigan, and Fort Knox, Kentucky. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1973Volume 78, Issue 5Page: 823-824KeywordsBlood urea nitrogenCellsGlobinsHemoglobinUreaUreases ePublished: 1 December 2008 Issue Published: 1 May 1973 PDF downloadLoading ...
Abstract 1758: Influence of stromal microenvironment on rGel/BLyS-induced cytotoxicity in diffuse large B-cell lymphoma cells
Authors: Mi-Ae Lyu, Lawrence H. Cheung, John W. Marks, Michael G. Rosenblum
Journal: Cancer Research (2011)

Abstract Diffuse large B cell lymphoma (DLBCL) is an aggressive sub-type accounting for 30-40% of non-Hodgkin's lymphoma. Despite recent advances in the understanding of the molecular and cellular basis for their pathogenesis, these tumors are still associated with poor response to treatment and a fatal outcome. The interactions of marrow stromal cells (MSCs) with tumor cells appear to be important in the development of tumor drug resistance through complex cytokine and adhesion-mediated mechanisms. We previously generated a highly cytotoxic growth factor fusion toxin designated rGel/BLyS for receptor-mediated delivery of the rGel toxin to malignant B cells. This fusion toxin specifically targets malignant B cells expressing the BLyS receptors BAFF-R, TACI, and BCMA. In this study, we examined the impact of marrow stromal cells (MSCs) on rGel/BLyS-induced cytotoxicity in DLBCL cells. Treatment of tumor cell lines with dexamethasone and doxorubicine in the presence of MSCs was found to suppress the cytotoxic effect. In contrast, in vitro treatment with rGel/BLyS showed specific cytotoxic effects to DLBCL cell lines (IC50 ∼ 1-10 nM) in absence of MSCs or in presence of MSCs. At these doses, we found no cytotoxicity to MSCs. Treatment with rGel/BLyS induced down-regulation of Mcl-1, c-Myc, Bcl-xL, X-IAP, and Bcl-2 in DLBCL cells in absence of MSCs or in presence of MSCs. We also found that rGel/BLyS induced down-regulation of interleukin-6 receptor in DLBCL cells in absence of MSCs or in presence of MSCs. In addition, treatment of cells with rGel/BLyS induced apoptosis through caspase-9 activation, caspase-3 activation, and PARP cleavage. Our results demonstrate that rGel/BLyS can overcome stromal cell-mediated drug resistance which is a factor reducing the effectiveness of other conventionally-used agents for the treatment of this disease. This suggests that rGel/BLyS may be an excellent candidate for the treatment of DLBCLs which are resistant to conventional chemotherapeutic regimens. This research was conducted, in part, by the Clayton Foundation for Research and by Translational Research Award (LLS 6234-07) from the Leukemia and Lymphoma Society. 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 1758. doi:10.1158/1538-7445.AM2011-1758
CD34+/Ph+ cells are still detectable in chronic myeloid leukemia patients with sustained and prolonged complete cytogenetic remission during treatment with imatinib mesylate
Authors: M Bocchia, M Ippoliti, A Gozzetti, E Abruzzese, S Calabrese, M Amabile, M T Pirrotta, R Crupi, D Tozzuoli, M M Trawinska, M Defina, G Martinelli, F Lauria
Journal: Leukemia (2007)
Exercise in Cardiovascular Health and Disease
Authors: David H. Spodick
Journal: JAMA (1978)

Exercise for diagnosis. Exercise for fitness. Exercise for treatment. Exercise for fun. One result of the mass interest in exercise in all its aspects is a mass of literature of varying quality. This book is one of the very good examples. The list of contributors bespeaks its authority: outstanding physicians in cardiovascular medicine and distinguished physical educators. The 26 chapters are replete with theoretical and practical information, including epidemiology and pathophysiology of coronary disease, exercise physiology, methodology and interpretation of exercise tests, preventive measures for coronary disease (including exercise prescription), physical fitness, risk factor modification, and rehabilitation. Uncertain areas are clearly labeled in a text that is free of the familiar hucksterism of exercise zealots and remarkably free—considering its scope—of errors, misstatements, and overlap. Uniformly lucid writing makes it difficult to pick among these outstanding essays. A sampler would include Wilmore's "Acute and Chronic Physiological Responses," Kattus's "Exercise Electrocardiography," Amsterdam