tbuckley/cabot-search huggingface dataset:
Adenoviral Human BCL-2 Transgene Expression Attenuates Early Donor Cell Death After Cardiomyoblast Transplantation Into Ischemic Rat Hearts
Authors: Ingo Kutschka, Theo Kofidis, Ian Y. Chen, Georges von Degenfeld, Monika Zwierzchoniewska, Grant Hoyt, Takayasu Arai, Darren R. Lebl, Stephen L. Hendry, Ahmad Y. Sheikh, David T. Cooke, Andrew Connolly, Helen M. Blau, Sanjiv S. Gambhir, Robert C. Robbins
Journal: Circulation (2006)

Background— Cell transplantation for myocardial repair is limited by early cell death. Gene therapy with human Bcl-2 (hBcl-2) has been shown to attenuate apoptosis in the experimental setting. Therefore, we studied the potential benefit of hBcl-2 transgene expression on the survival of cardiomyoblast grafts in ischemic rat hearts. Methods and Results— H9c2 rat cardiomyoblasts were genetically modified to express both firefly luciferase and green fluorescent protein (mH9c2). The cells were then transduced with adenovirus carrying hBcl-2 (AdCMVhBcl-2/mH9c2). Lewis rats underwent ligation of the left anterior descending artery (LAD) to induce a sizable left ventricular (LV) infarct. Hearts were explanted and the infarcted region was restored using collagen matrix (CM) seeded with 1×10 6 mH9c2 cells (n=9) or AdCMVhBcl-2/mH9c2 cells (n=9). Control animals received CM alone (n=6) or no infarct (n=6). Restored hearts were transplanted into the abdomen of syngeneic recipients in a “working heart” model. Cell survival was evaluated using optical bioluminescence imaging on days 1, 5, 8, 14, and 28 after surgery. The left heart function was assessed 4 weeks postoperatively using echocardiography and magnetic resonance imaging. During 4 weeks after surgery, the optical imaging signal for the AdCMVhBCL2/mH9c2 group was significantly ( P &lt;0.05) higher than that of the mH9c2-control group. Both grafts led to better fractional shortening (AdCMVhBcl-2/mH9c2: 0.21±0.03; mH9c2: 0.21±0.04; control: 0.15±0.03; P =0.04) and ejection fraction (AdCMVhBcl-2/mH9c2: 47.0±6.2; mH9c2: 48.7±6.1; control: 34.3±6.0; P =0.02) compared with controls. Importantly, no malignant cells were found in postmortem histology. Conclusion— Transduction of mH9c2 cardiomyoblasts with AdCMVhBcl-2 increased graft survival in ischemic rat myocardium without causing malignancies. Both AdCMVhBcl-2/mH9c2 and mH9c2 grafts improved LV function.
Report of the consensus conference on acne classification
Authors: Peter E. Pochi, Alan R. Shalita, John S. Strauss, Stephen B. Webster, William J. Cunliffe, H. Irving Katz, Albert M. Kligman, James J. Leyden, Donald P. Lookingbill, Gerd Plewig, Ronald M. Reisner, Orlando G. Rodman, Maria L. Turner, Guy F. Webster
Journal: Journal of the American Academy of Dermatology (1991)
Deregulation of the FOXM1 target gene network and its coregulatory partners in oesophageal adenocarcinoma
Authors: Elizabeth F Wiseman, Xi Chen, Namshik Han, Aaron Webber, Zongling Ji, Andrew D Sharrocks, Yeng S Ang
Journal: Molecular Cancer (2015)

Survival rates for oesophageal adenocarcinoma (OAC) remain disappointingly poor and current conventional treatment modalities have minimal impact on long-term survival. This is partly due to a lack of understanding of the molecular changes that occur in this disease. Previous studies have indicated that the transcription factor FOXM1 is commonly upregulated in this cancer type but the impact of this overexpression on gene expression in the context of OAC is largely unknown. FOXM1 does not function alone but works alongside the antagonistically-functioning co-regulatory MMB and DREAM complexes.To establish how FOXM1 affects gene expression in OAC we have identified the FOXM1 target gene network in OAC-derived cells using ChIP-seq and determined the expression of both its coregulatory partners and members of this target gene network in OAC by digital transcript counting using the Nanostring gene expression assay.We find co-upregulation of FOXM1 with its target gene network in OAC. Furthermore, we find changes in the expression of its coregulatory partners, including co-upregulation of LIN9 and, surprisingly, reduced expression of LIN54. Mechanistically, we identify LIN9 as the direct binding partner for FOXM1 in the MMB complex. In the context of OAC, both coregulator (eg LIN54) and target gene (eg UHRF1) expression levels are predictive of disease stage.Together our data demonstrate that there are global changes to the FOXM1 regulatory network in OAC and the expression of components of this network help predict cancer prognosis.
Comparison of Pioglitazone and Gliclazide in Sustaining Glycemic Control Over 2 Years in Patients With Type 2 Diabetes
Authors: Meng H. Tan, Arun Baksi, Boris Krahulec, Piotr Kubalski, Andrzej Stankiewicz, Richard Urquhart, Gareth Edwards, Don Johns
Journal: Diabetes Care (2005)

OBJECTIVE—The hypothesis that pioglitazone treatment is superior to gliclazide treatment in sustaining glycemic control for up to 2 years in patients with type 2 diabetes was tested. RESEARCH DESIGN AND METHODS—This was a randomized, multicenter, double-blind, double-dummy, parallel-group, 2-year study. Approximately 600 patients from 98 centers participated. Eligible patients had completed a previous 12-month study and consented to continue treatment for a further year. To avoid selection bias, all patients from all centers were included in the primary analysis (a comparison of the time-to-failure distributions of the two groups by using a log-rank test) regardless of whether they continued treatment for a 2nd year. By using repeated-measures ANOVA, time course of least square means of HbA1c and homeostasis model of assessment (HOMA) indexes (HOMA-%S and HOMA-%B) were analyzed. RESULTS—A greater proportion of patients treated with pioglitazone maintained HbA1c &amp;lt;8% over the 2-year period than those treated with gliclazide. A difference between the Kaplan-Meier curves was apparent as early as week 32 and widened at each time point thereafter, becoming statistically significant from week 52 onward. At week 104, 129 (47.8%) of 270 pioglitazone-treated patients and 110 (37.0%) of 297 gliclazide-treated patients maintained HbA1c &amp;lt;8%. Compared with gliclazide treatment, pioglitazone treatment produced a larger decrease in HbA1c, a larger increase in HOMA-%S, and a smaller increase in HOMA-%B during the 2nd year of treatment. CONCLUSIONS—Pioglitazone is superior to gliclazide in sustaining glycemic control in patients with type 2 diabetes during the 2nd year of treatment.
Cracking the Estrogen Receptor's Posttranslational Code in Breast Tumors
Authors: Muriel Le Romancer, Coralie Poulard, Pascale Cohen, Stéphanie Sentis, Jack-Michel Renoir, Laura Corbo
Journal: Endocrine Reviews (2011)

Estrogen signaling pathways, because of their central role in regulating the growth and survival of breast tumor cells, have been identified as suitable and efficient targets for cancer therapies. Agents blocking estrogen activity are already widely used clinically, and many new molecules have entered clinical trials, but intrinsic or acquired resistance to treatment limits their efficacy. The basic molecular studies underlying estrogen signaling have defined the critical role of estrogen receptors (ER) in many aspects of breast tumorigenesis. However, important knowledge gaps remain about the role of posttranslational modifications (PTM) of ER in initiation and progression of breast carcinogenesis. Whereas major attention has been focused on the phosphorylation of ER, many other PTM (such as acetylation, ubiquitination, sumoylation, methylation, and palmitoylation) have been identified as events modifying ER expression and stability, subcellular localization, and sensitivity to hormonal response. This article will provide an overview of the current and emerging knowledge on ER PTM, with a particular focus on their deregulation in breast cancer. We also discuss their clinical relevance and the functional relationship between PTM. A thorough understanding of the complete picture of these modifications in ER carcinogenesis might not only open new avenues for identifying new markers for prognosis or prediction of response to endocrine therapy but also could promote the development of novel therapeutic strategies.
Molecular Pathways: Adiponectin and Leptin Signaling in Cancer
Authors: Michael N. VanSaun
Journal: Clinical Cancer Research (2013)

Abstract The increasing percentage of obese individuals in the population and its independent association of increased risk for the development of cancer have heightened the necessity to understand the molecular mechanisms that underlie this connection. The deregulation of adipokines in the setting of obesity and their impact on cancer progression and metastasis is one such area of research. Adipokines are bioactive proteins that mediate metabolism, inflammation, angiogenesis, and proliferation. Altered levels of adipokines or their cognate receptors in cancers can ultimately lead to an imbalance in downstream molecular pathways. Discovery of adipokine receptors in various cancers has highlighted the potential for novel therapeutic targets. Leptin and adiponectin represent two adipokines that elicit generally opposing molecular effects. Epidemiologic studies have highlighted associations between increased serum leptin levels and increased tumor growth, whereas adiponectin exhibits an inverse correlation with cancer development. This review addresses the current level of understanding of molecular pathways activated by adiponectin and leptin to identify the areas of intervention and facilitate advancement in the field. Clin Cancer Res; 19(8); 1926–32. ©2013 AACR.
Similar 9-year mortality risks and reproducibility for the World Health Organization and American Diabetes Association glucose tolerance categories: the Hoorn Study.
Authors: F de Vegt, J M Dekker, C D Stehouwer, G Nijpels, L M Bouter, R J Heine
Journal: Diabetes Care (2000)

OBJECTIVE: To compare the risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association (ADA) and World Health Organization (WHO) glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. RESEARCH DESIGN AND METHODS: In this population-based cohort study of 2,468 elderly men and women, subjects were classified according to both the WHO and the ADA criteria. Causes of death were extracted from the medical records. Age- and sex-adjusted relative risks were estimated by Cox's proportional hazards model. Reproducibility of the diagnostic criteria was assessed in a sample of 1,109 subjects with duplicate oral glucose tolerance tests. RESULTS: Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects (P&amp;lt;0.05). The relative risks of all-cause mortality were 1.67 (95% CI 1.09-2.57) and 1.56 (1.00-2.43) for newly diagnosed diabetic subjects according to the WHO and ADA criteria, respectively. The WHO and ADA criteria had similar levels of reproducibility The overall K was 0.59 (0.54-0.64) for WHO criteria and 0.61 (0.56-0.66) for ADA criteria. For the category of newly diagnosed diabetes according to WHO or ADA, the percentages of agreement for the second test compared with the first test were 77% (85/110) and 74% (74/100), respectively. CONCLUSIONS: Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.
Macrophage MicroRNA-155 Promotes Cardiac Hypertrophy and Failure
Authors: Stephane Heymans, Maarten F. Corsten, Wouter Verhesen, Paolo Carai, Rick E.W. van Leeuwen, Kevin Custers, Tim Peters, Mark Hazebroek, Lauran Stöger, Erwin Wijnands, Ben J. Janssen, Esther E. Creemers, Yigal M. Pinto, Dirk Grimm, Nina Schürmann, Elena Vigorito, Thomas Thum, Frank Stassen, Xiaoke Yin, Manuel Mayr, Leon J. de Windt, Esther Lutgens, Kristiaan Wouters, Menno P.J. de Winther, Serena Zacchigna, Mauro Giacca, Marc van Bilsen, Anna-Pia Papageorgiou, Blanche Schroen
Journal: Circulation (2013)

Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this process. We recently reported that microRNA-155 is a key mediator of cardiac inflammation and injury in infectious myocarditis. Here, we investigated the impact of microRNA-155 manipulation in hypertensive heart disease.Genetic loss or pharmacological inhibition of the leukocyte-expressed microRNA-155 in mice markedly reduced cardiac inflammation, hypertrophy, and dysfunction on pressure overload. These alterations were macrophage dependent because in vivo cardiomyocyte-specific microRNA-155 manipulation did not affect cardiac hypertrophy or dysfunction, whereas bone marrow transplantation from wild-type mice into microRNA-155 knockout animals rescued the hypertrophic response of the cardiomyocytes and vice versa. In vitro, media from microRNA-155 knockout macrophages blocked the hypertrophic growth of stimulated cardiomyocytes, confirming that macrophages influence myocyte growth in a microRNA-155-dependent paracrine manner. These effects were at least partly mediated by the direct microRNA-155 target suppressor of cytokine signaling 1 (Socs1) because Socs1 knockdown in microRNA-155 knockout macrophages largely restored their hypertrophy-stimulating potency.Our findings reveal that microRNA-155 expression in macrophages promotes cardiac inflammation, hypertrophy, and failure in response to pressure overload. These data support the causative significance of inflammatory signaling in hypertrophic heart disease and demonstrate the feasibility of therapeutic microRNA targeting of inflammation in heart failure.
Living organ donation
Authors: T. Jackson
Journal: BMJ (2003)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Living organ donation Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Radiosurgery alone or in combination with whole-brain radiotherapy for brain metastases.
Authors: A Pirzkall, J Debus, F Lohr, M Fuss, B Rhein, R Engenhart-Cabillic, M Wannenmacher
Journal: Journal of Clinical Oncology (1998)

PURPOSE Evaluation of the treatment outcome after radiosurgery (RS) alone or in combination with whole-brain radiotherapy (WBRT) with special attention to prescribed dose and its influence on local control and survival. PATIENTS AND METHODS Between September 1984 and January 1997, 236 patients with 311 brain metastases treated with radiosurgery met the following inclusion criteria: one to three brain metastases per patient; no previous WBRT; and Kamofsky performance status (KPS) &gt; or = 50%. One hundred fifty-eight patients treated only with RS received a median dose of 20 Gy prescribed to the 80% isodose line; 78 patients received RS with a median dose of 15 Gy/80% and an additional course of WBRT. RESULTS For the entire series, overall median survival was 5.5 months, with control of CNS disease achieved in 92% of the treated brain metastases; the results were not significantly different between patients treated by RS with or without WBRT. However, in patients without evidence of extracranial disease, median survival was increased for patients who received WBRT (15.4 vs 8.3 months; P=.08). Additionally, there was a suggestion that increased doses for patients treated with RS only resulted in improved outcome. Four lesions were suspicious for radiation necrosis by magnetic resonance imaging (MRI); in one of the four lesions, radiation necrosis was confirmed histologically. The incidence of transient low-grade toxicity was 18%; symptoms could be treated by the temporary administration of steroids. CONCLUSION RS is an effective, noninvasive means of controlling brain metastases when used alone or in combination with WBRT. There is a trend for superior local control and especially in patients without extracranial disease for superior survival when RS is used in conjunction with WBRT. Randomized trials would seem to be warranted, comparing the benefit of RS with or without additional WBRT.
Thromboembolism—Another Threat to the Polymorbid Patient with Vasculitis?
Authors: P Merkel, GH Lo, JT Holbrook, AK Tibbs, NB Allen, JC Davis, GS Hoffman, WJ McCune, EW St Clair, U Specks, R Spiera, M Petri, JH Stone
Journal: Journal of the American Society of Nephrology (2005)

Patients with Wegener’s disease are known to suffer from a wide spectrum of pathology resulting from inflammatory lesions of small and medium-sized arterial vessels. Indeed, the definition of Wegener’s disease is based upon the localization of the typical lesions in the arterial vessels ([1][1
Age, Sex, and Racial Differences in the Use of Standard Adjuvant Therapy for Colorectal Cancer
Authors: Arnold L. Potosky, Linda C. Harlan, Richard S. Kaplan, Karen A. Johnson, Charles F. Lynch
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Dissemination of efficacious adjuvant therapies for resectable colorectal cancer has not been comprehensively described. Trends, patterns, and outcomes of adjuvant therapy for colorectal cancer, focusing on age, sex, and racial/ethnic differences, are reported. MATERIALS AND METHODS: Population-based random samples of patients diagnosed with colorectal cancer diagnosed in nine geographic areas were collected annually between 1987 and 1991 and in 1995 (n = 4,706). Data were obtained from medical record reviews. Multiple logistic regression was used to assess the use of standard adjuvant chemotherapy for colon and rectal cancers. The Cox proportional hazards model was used to assess 9-year mortality. RESULTS: From 1987 until 1995, the use of adjuvant therapy increased in all age groups. There was an increase starting in 1989 for colon and in 1988 for rectal cancer. Use of standard therapy was 78% for those younger than 55 years and 24% for those older than 80 years. White patients received standard therapy more frequently than African-Americans (odds ratio, 1.75; 95% confidence interval [CI], 1.09 to 2.83). All-cause and cancer-specific mortality exceeding 9 years were lower in those who received standard therapy (all-cause risk ratio [RR], 0.73; 95% CI, 0.61 to 0.88; cancer-specific RR, 0.87; 95% CI, 0.70 to 1.09). CONCLUSION: Standard adjuvant therapies for colorectal cancer disseminated into community practices during the 1990s. However, evidence exists of differential use of therapies by older patients and by African-Americans. The use of standard therapies in the general population is associated with lower mortality. Improved dissemination of standard adjuvant therapies to all segments of the population could help reduce mortality.
Role of the transient outward potassium current in the genesis of early afterdepolarizations in cardiac cells
Authors: Zhenghang Zhao, Yuanfang Xie, Hairuo Wen, Dandan Xiao, Charelle Allen, Nadezhda Fefelova, Wen Dun, Penelope A. Boyden, Zhilin Qu, Lai-Hua Xie
Journal: Cardiovascular Research (2012)

The transient outward potassium current (Ito) plays important roles in action potential (AP) morphology and dynamics; however, its role in the genesis of early afterdepolarizations (EADs) is not well understood. We aimed to study the effects and mechanisms of Ito on EAD genesis in cardiac cells using combined experimental and computational approaches. We first carried out patch-clamp experiments in isolated rabbit ventricular myocytes exposed to H2O2 (0.2 or 1 mM), in which EADs were induced at a slow pacing rate. EADs were eliminated by either increasing the pacing rate or blocking Ito with 2 mM 4-aminopyridine. In addition to enhancing the L-type calcium current (ICa,L) and the late sodium current, H2O2 also increased the conductance, slowed inactivation, and accelerated recovery from the inactivation of Ito. Computer simulations showed that Ito promoted EADs under the condition of reduced repolarization reserve, consistent with the experimental observations. However, EADs were only promoted in the intermediate ranges of the Ito conductance and the inactivation time constant. The underlying mechanism is that Ito lowers the AP plateau voltage into the range at which the time-dependent potassium current (namely IKs) activation is further slowed and ICa,L is available for reactivation, leading to voltage oscillations to manifest EADs. Further experimental studies in cardiac cells of other species validated the theoretical predictions. In cardiac cells, Ito, with a proper conductance and inactivation speed, potentiates EADs by setting the AP plateau into the voltage range where ICa,L reactivation is facilitated and IKs activation is slowed.
Purinogenic Immunodeficiency Diseases
Authors: James M. Wilson, Beverly S. Mitchell, Peter E. Daddona, William N. Kelley
Journal: Journal of Clinical Investigation (1979)

Deoxyadenosine and deoxyguanosine are toxic to human lymphoid cells in culture and have been implicated in the pathogenesis of the immunodeficiency states associated with adenosine deaminase and purine nucleoside phosphorylase deficiency, respectively. We have studied the relative incorporation of several labeled nucleosides into DNA and into nucleotide pools to further elucidate the mechanism of deoxyribonucleoside toxicity. In the presence of an inhibitor of adenosine deaminase [erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA], 5 μM], deoxyadenosine (1-50 μM) progressively decreased the incorporation of thymidine, uridine, and deoxyuridine into DNA, but did not affect uridine incorporation into RNA. This decrease in DNA synthesis was associated with increasing dATP and decreasing dCTP pools. Likewise, incubation of cells with deoxyguanosine caused an elevation of dGTP, depletion of dCTP, and inhibition of DNA synthesis.
The economic burden of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
Authors: B.Y. Lee, A. Singh, M.Z. David, S.M. Bartsch, R.B. Slayton, S.S. Huang, S.M. Zimmer, M.A. Potter, C.M. Macal, D.S. Lauderdale, L.G. Miller, R.S. Daum
Journal: Clinical Microbiology and Infection (2012)
Imiquimod in the treatment of lentigo maligna
Authors: S.F. Rajpar, J.R. Marsden
Journal: British Journal of Dermatology (2006)

Journal Article Imiquimod in the treatment of lentigo maligna Get access S.F. Rajpar, S.F. Rajpar Skin Oncology Service, University Hospital Birmingham NHS Trust, Birmingham B29 6JD, U.K Sajjad Rajpar. E‐mail: sfr@blueyonder.co.uk Search for other works by this author on: Oxford Academic Google Scholar J.R. Marsden J.R. Marsden Skin Oncology Service, University Hospital Birmingham NHS Trust, Birmingham B29 6JD, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 155, Issue 4, 1 October 2006, Pages 653–656, https://doi.org/10.1111/j.1365-2133.2006.07476.x Published: 01 October 2006 Article history Accepted: 15 May 2006 Published: 01 October 2006