tbuckley/cabot-search huggingface dataset:
Smooth Muscle Expression of Lipoma Preferred Partner Is Mediated by an Alternative Intronic Promoter That Is Regulated by Serum Response Factor/Myocardin
Authors: Marleen M.R. Petit, Henrik Lindskog, Erik Larsson, Per Wasteson, Elisabeth Athley, Silke Breuer, Meike Angstenberger, David Hertfelder, Erney Mattsson, Alfred Nordheim, Sven Nelander, Per Lindahl
Journal: Circulation Research (2008)

Lipoma preferred partner (LPP) was recently recognized as a smooth muscle marker that plays a role in smooth muscle cell migration. In this report, we focus on the transcriptional regulation of the LPP gene. In particular, we investigate whether LPP is directly regulated by serum response factor (SRF). We show that the LPP gene contains 3 evolutionarily conserved CArG boxes and that 1 of these is part of an alternative promoter in intron 2. Quantitative RT-PCR shows that this alternative promoter directs transcription specifically to smooth muscle containing tissues in vivo. By using chromatin immunoprecipitation, we demonstrate that 2 of the CArG boxes, including the promoter-associated CArG box, bind to endogenous SRF in cultured aortic smooth muscle cells. Electrophoretic mobility-shift assays show that the conserved CArG boxes bind SRF in vitro. In reporter experiments, we show that the alternative promoter has transcriptional capacity that is dependent on SRF/myocardin and that the promoter associated CArG box is required for that activity. Finally, we show by quantitative RT-PCR that the alternative promoter is strongly downregulated in SRF-deficient embryonic stem cells and in smooth muscle tissues derived from conditional SRF knockout mice. Collectively, our data demonstrate that expression of LPP in smooth muscle is mediated by an alternative promoter that is regulated by SRF/myocardin.
Abdominal pain in long distance runners: case report and analysis of the literature
Authors: F C Dimeo, J Peters, H Guderian
Journal: British Journal of Sports Medicine (2004)

Abdominal pain is a common complaint among participants in endurance sports. It may be severe, recurrent, and resistant to treatment. There is no direct evidence of the cause of this phenomenon. This report is of a long distance runner who had severe pain in the upper right abdominal quadrant during strenuous exertion. The symptom had been present for several years and did not respond to conservative treatment. Laparoscopy showed congenital supernumerary ligaments binding the gallbladder to the abdominal wall. The complaint resolved after cholecystectomy and resection of adhesions. There was evidence of chronic cholecystitis on histopathological examination. Two years after the operation, he remains free of symptoms. The differential diagnosis of abdominal pain in athletes is discussed.
Phase II Study of 9-Nitro-Camptothecin in Patients With Advanced Chordoma or Soft Tissue Sarcoma
Authors: Rashmi Chugh, Rodney Dunn, Mark M. Zalupski, J. Sybil Biermann, Vernon K. Sondak, Joseph R. Mace, Kirsten M. Leu, William F. Chandler, Laurence H. Baker
Journal: Journal of Clinical Oncology (2005)

Purpose The purpose of this trial was to assess the objective clinical response, toxicity, and time to progression of treatment with 9-Nitro-Camptothecin (9-NC) in patients with advanced chordoma, soft tissue sarcoma (STS), and gastrointestinal stromal tumor (GIST). Patients and Methods Patients with locally advanced and/or metastatic chordoma, STS, or GIST received 9-NC 1.25 mg/m 2 orally for 5 consecutive days followed by 2 days of rest. Patients continued on therapy until disease progression, uncontrollable toxicity, or withdrawal of consent. Results From January 2000 to May 2003, 51 patients (15 chordoma, 23 STS, 13 GIST patients) enrolled. One patient (7%) with chordoma and one patient (4%) with STS had an objective response. Median time to progression was 9.9, 8.0, and 8.3 weeks for chordoma, STS, and GIST patients, respectively. Three- and 6-month progression-free survival rates were 47% and 33% for chordoma patients, 26% and 22% for STS patients, and 31% and 23% for GIST patients, respectively. Ten patients (10%) stopped study drug before disease progression secondary to toxicity. Common adverse events included anemia (42 patients, seven with grade 3/4 toxicity), leukopenia (33 patients, nine with grade 3/4 toxicity), fatigue (30 patients, three with grade 3/4 toxicity), nausea (34 patients, six with grade 3/4 toxicity), and diarrhea (28 patients, five with grade 3/4 toxicity). Conclusion 9-NC has modest activity in delaying progression in patients with unresectable or metastatic chordoma. 9-NC is associated with moderate toxicity and shows little benefit in patients with advanced STS and GIST.
The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune Encephalomyelitis
Authors: Naoto Kawakami, Silke Lassmann, Zhaoxia Li, Francesca Odoardi, Thomas Ritter, Tjalf Ziemssen, Wolfgang E.F. Klinkert, Joachim W. Ellwart, Monika Bradl, Kimberly Krivacic, Hans Lassmann, Richard M. Ransohoff, Hans-Dieter Volk, Hartmut Wekerle, Christopher Linington, Alexander Flügel
Journal: The Journal of Experimental Medicine (2004)

The clinical picture of experimental autoimmune encephalomyelitis (EAE) is critically dependent on the nature of the target autoantigen and the genetic background of the experimental animals. Potentially lethal EAE is mediated by myelin basic protein (MBP)–specific T cells in Lewis rats, whereas transfer of S100β- or myelin oligodendrocyte glycoprotein (MOG)–specific T cells causes intense inflammatory response in the central nervous system (CNS) with minimal disease. However, in Dark Agouti rats, the pathogenicity of MOG-specific T cells resembles the one of MBP-specific T cells in the Lewis rat. Using retrovirally transduced green fluorescent T cells, we now report that differential disease activity reflects different levels of autoreactive effector T cell activation in their target tissue. Irrespective of their pathogenicity, the migratory activity, gene expression patterns, and immigration of green fluorescent protein+ T cells into the CNS were similar. However, exclusively highly pathogenic T cells were significantly reactivated within the CNS. Without local effector T cell activation, production of monocyte chemoattractants was insufficient to initiate and propagate a full inflammatory response. Low-level reactivation of weakly pathogenic T cells was not due to anergy because these cells could be activated by specific antigen in situ as well as after isolation ex vivo.
Neuroleptic Concentrations and Clinical Response
Authors: L Rivera-Calimlim, L Hershey
Journal: The Annual Review of Pharmacology and Toxicology (1984)

The clinical effectiveness of antipsychotic chemotherapy has been proven worldwide, yet a multitude of problems remain concerning that significant percent of the target population who do not benefit from such chemotherapy. Since the introduction of chlorpromazine in the early 1950s, other phe­ nothiazines, the butyrophenones, the thioxanthenes, the dihydroindolones, and the dibenzoxazepines have been introduced and have proven therapeutically effective with varying degrees of potency and side effects( 1). Non-responders to chlorpromazine have responded to some of the newer drugs, but the param­ eters of safe and effective dosage remain to be set. In the many uncontrolled and controlled clinical trials and anecdotal case reports, drug dosing has been mainly empirical, based on pushing doses to toxic levels or on a trial-and-error titration of dose and clinical effect. The lack of therapeutic guidelines in the clinical use of the antipsychotic drugs has moved interested groups to attack the problem of wide variability in drug dosage and clinical response among psychiatric patients. The introduction of sensitive antipsychotic drug assays in biologic fluids (2) revolutionized phannacokinetic and pharmacodynamic knowledge about the various antipsychotic drugs used in different types of clinical disorders. It
Abstract 2561: Inhibiting the mTOR pathway synergistically enhances etoposide-induced cytotoxicity by upregulating c-Jun in ovarian cancer cells
Authors: Hiroaki Itamochi, Michiko Nonaka, Seiya Sato, Kazunori Uegaki, Jun Naniwa, Shinya Sato, Muneaki Shimada, Oishi Tetsuro, Naoki Terakawa, Junzo Kigawa, Tasuku Harada
Journal: Cancer Research (2011)

Abstract Objective: The mammalian target of rapamycin (mTOR) pathway is considered to be a central regulator of proliferation and survival of cells. Rapamycin and its analogs are undergoing clinical trials in patients with epithelial ovarian cancer. Rapamycin has been reported to enhance the effectiveness of several chemotherapeutic agents. The present study aimed to assess the potential of combination effects of rapamycin and anticancer drugs used as first- or second-line chemotherapy to treat ovarian cancer. Methods: Six cell lines of ovarian serous adenocarcinoma (KF, KOC-2S, SHIN-3, SK-OV-3, TU-OS-3, TU-OS-4) were used in this study. We treated the cells with rapamycin combined with anticancer agents, then assessed cell viability, apoptosis, and the expression of proteins in apoptotic pathways and molecules downstream of the mTOR signaling pathways. We also investigated the effect of combined treatment on survival in xenograft models with nude mice. Results: The protein expression levels of PTEN, phosphorylated (p) Akt, pmTOR, p4E-BP1, and pS6K1 were confirmed in all cell lines. Synergistic effects with rapamycin were observed in combination with etoposide in five cell lines, with doxorubicin in four lines, and with SN38, which is an active metabolite of camptothecin-11, in two lines. However, we observed antagonistic effects when rapamycin was combined with gemcitabine, cisplatin, or paclitaxel on more than two cell lines. Rapamycin dramatically enhanced apoptosis induced by etoposide and the expression of cleaved caspase 9. This effect was associated with up-regulation of phosphorylated c-Jun and down-regulation of Bcl-xL. The synergistic interaction of rapamycin and etoposide was lower when the c-Jun pathway was suppressed by a c-Jun N-terminal kinase inhibitor (SP600125). Finally, treating nude mice with rapamycin and etoposide significantly prolonged survival in model mice with ovarian cancer xenografts (P&amp;lt;0.001). Conclusion: Combination chemotherapy consisting of rapamycin and etoposide showed synergistic effect against epithelial ovarian cancer. This treatment modality is worth exploring further for patients with ovarian cancer. 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 2561. doi:10.1158/1538-7445.AM2011-2561
Androgen Levels Increase by Intratumoral <i>De novo</i> Steroidogenesis during Progression of Castration-Resistant Prostate Cancer
Authors: Jennifer A. Locke, Emma S. Guns, Amy A. Lubik, Hans H. Adomat, Stephen C. Hendy, Catherine A. Wood, Susan L. Ettinger, Martin E. Gleave, Colleen C. Nelson
Journal: Cancer Research (2008)

Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of a castration-resistant prostate cancer (CRPC) as indicated by recurring PSA. This complex process of progression does not seem to be stochastic as the timing and phenotype are highly predictable, including the observation that most androgen-regulated genes are reactivated despite castrate levels of serum androgens. Recent evidence indicates that intraprostatic levels of androgens remain moderately high following systemic androgen deprivation therapy, whereas the androgen receptor (AR) remains functional, and silencing the AR expression following castration suppresses tumor growth and blocks the expression of genes known to be regulated by androgens. From these observations, we hypothesized that CRPC progression is not independent of androgen-driven activity and that androgens may be synthesized de novo in CRPC tumors leading to AR activation. Using the LNCaP xenograft model, we showed that tumor androgens increase during CRPC progression in correlation to PSA up-regulation. We show here that all enzymes necessary for androgen synthesis are expressed in prostate cancer tumors and some seem to be up-regulated during CRPC progression. Using an ex vivo radiotracing assays coupled to high-performance liquid chromatography-radiometric/mass spectrometry detection, we show that tumor explants isolated from CRPC progression are capable of de novo conversion of [(14)C]acetic acid to dihydrotestosterone and uptake of [(3)H]progesterone allows detection of the production of six other steroids upstream of dihydrotestosterone. This evidence suggests that de novo androgen synthesis may be a driving mechanism leading to CRPC progression following castration.
Collagen in the human lung. Quantitation of rates of synthesis and partial characterization of composition.
Authors: K Bradley, S McConnell-Breul, R G Crystal
Journal: Journal of Clinical Investigation (1975)

The presence of collagen in lung is fundamental in normal lung structure and function. Methods have been developed to examine human fetal and adult lung collagen with respect to its composition and synthesis. The second trimester fetal lung has a large number of cells per unit lung mass (36.6 plus or minus 2.7 mug DNA/mg dry wt) and relatively small amounts of collagen (17.0 plus or minus 5.3 mug collagen/mg dry wt). The number of cells per unit lung mass in the adult lung (11.1 plus or minus 3.4 mug DNA/mg dry wt) is 30% of the number of cells in the fetal lung, but the adult has 11 times more collagen (196 plus or minus 25 mug collagen/mg dry wt). The composition of fetal lung collagen can be partially characterized by extraction with salt at neutral pH, acetic acid, or guanidine. The extracted chains, representing 10% of the total lung collagen, chromatograph as alpha1 and alpha2 chains, each with a mol wt of 100,000 and an animo acid composition characteristic for collagen but not specific for lung. Short-term explant cultures of fetal and adult lung synthesize alpha chains which can be isolated by ion-exchange chromatography. These chains, representing 30-40% of the total collagen synthesized by the explants, coelectrophorese with extracted collagen chains on acrylamide gels: they are destroyed by clostridial collagenase and they have a mol wt of 100,000. Although the composition of the collagen synthesized by these explants can be only partially characterized, the rate of synthesis of both collagen and noncollagen protein can be quantitated. In fetal lung, 4.0 plus or minus 1.2% of the amino acids incorporated into protein per hour are incorporated into collagen. In normal adult lung, this percentage (4.2 plus or minus 0.9%) is remarkably similar. These values are almost identical to the relative rate of collagen synthesis in rabbit lung in the same age range. This technology should be applicable to answer specific questions regarding collagen synthesis and degradation in human lung disease.
Prospective Study of Plasma Fatty Acids and Risk of Prostate Cancer
Authors: P H Gann, C H Hennekens, F M Sacks, F Grodstein, E L Giovannucci, M J Stampfer
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Prospective Study of Plasma Fatty Acids and Risk of Prostate Cancer Get access Peter H. Gann, Peter H. Gann Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles H. Hennekens, Charles H. Hennekens Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank M. Sacks, Frank M. Sacks Search for other works by this author on: Oxford Academic PubMed Google Scholar Francine Grodstein, Francine Grodstein Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward L. Giovannucci, Edward L. Giovannucci Search for other works by this author on: Oxford Academic PubMed Google Scholar Meir J. Stampfer Meir J. Stampfer * * Correspondence to: Peter H. Gann, M.D., Department of Preventive Medicine, North western University School of Medicine, 680 N Lake Shore Dr., Suite 1102, Chicago, IL 60611 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 4, 16 February 1994, Pages 281–286, https://doi.org/10.1093/jnci/86.4.281 Published: 16 February 1994 Article history Received: 08 July 1993 Revision received: 04 November 1993 Accepted: 26 November 1993 Published: 16 February 1994
Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis
Authors: Hideki Makishima, Valeria Visconte, Hirotoshi Sakaguchi, Anna M. Jankowska, Sarah Abu Kar, Andres Jerez, Bartlomiej Przychodzen, Manoj Bupathi, Kathryn Guinta, Manuel G. Afable, Mikkael A. Sekeres, Richard A. Padgett, Ramon V. Tiu, Jaroslaw P. Maciejewski
Journal: Blood (2012)
Interleukin-17 causes Rho-kinase-mediated endothelial dysfunction and hypertension
Authors: Hoanglan Nguyen, Valorie L. Chiasson, Piyali Chatterjee, Shelley E. Kopriva, Kristina J. Young, Brett M. Mitchell
Journal: Cardiovascular Research (2012)

AimsElevated levels of pro-inflammatory cytokine interleukin-17A (IL-17) are associated with hypertensive autoimmune diseases; however, the connection between IL-17 and hypertension is unknown. We hypothesized that IL-17 increases blood pressure by decreasing endothelial nitric oxide production.
Oesophageal reconstruction for complete stenosis due to dystrophic epidermolysis bullosa.
Authors: S Sehhat, S A Amirie
Journal: Thorax (1977)

Oesophageal involvement in epidermolysis bullosa is discussed. Two patients, a brother and sister, with stricture of the oesophagus due to the disease are described. The strictures were treated by resection and end-to-end oesophageal anastomosis and the patients have been relieved of dysphagia for the subsequent three years.
Extensive mutational status of genes and clinical outcome in pediatric acute myeloid leukemia
Authors: H Lapillonne, L Llopis, A Auvrignon, A Renneville, M Labopin, F Mazingue, C Perot, J-L Lai, N Philippe, P Ballerini, V Zurawski, M Adam, L Douay, G Leverger, J Landman-Parker, C Preudhomme
Journal: Leukemia (2009)
Analysis of dihydrofolate reductase and reduced folate carrier gene status in relation to methotrexate resistance in osteosarcoma cells
Authors: M. Serra, G. Reverter-Branchat, D. Maurici, S. Benini, J.-N. Shen, T. Chano, C.-M. Hattinger, M.-C. Manara, M. Pasello, K. Scotlandi, P. Picci
Journal: Annals of Oncology (2003)
Unadjusted and Adjusted Prevalence of Diagnosed Depression in Type 2 Diabetes
Authors: Gregory A. Nichols, Jonathan B. Brown
Journal: Diabetes Care (2003)

To estimate the prevalence of diagnosed depression in a large population of individuals with type 2 diabetes, compared to a matched control group, and to estimate the extent of depression that is independently associated with diabetes.We compared the prevalence of diagnosed depression in all 16180 full-year health maintenance organization members in 1999 who had been diagnosed with type 2 diabetes and in 16180 comparison members without diabetes matched for age and sex. We ascertained diagnoses from the Kaiser Permanente Northwest Region's electronic medical record. Using multiple logistic regression, we adjusted the prevalence estimates for the presence of cardiovascular disease, age, sex, and body weight.Depression was more common in individuals with type 2 diabetes than among matched control subjects (17.9 vs. 11.2%; P < 0.001). Women in both groups were nearly twice as likely to be depressed as men; however, the relative difference in depression prevalence between subjects with and without diabetes was greater in men. In the multivariate model for women, body weight was a much stronger predictor of depression than diabetes status.This study further documents the association between depression and diabetes, providing unadjusted population-based estimates in a large sample. Depression remained associated with diabetes after adjustment for several other possible causes. The association among diabetes, cardiovascular disease, depression, and obesity are multifaceted and differ for men and women.
Bradykinin generation by dialysis membranes
Authors: G Schulman, R Hakim, R Arias, M Silverberg, A P Kaplan, L Arbeit
Journal: Journal of the American Society of Nephrology (1993)

Several recent reports have described a high incidence of anaphylactic reactions in patients being dialyzed with high-flux membranes while simultaneously using angiotensin-converting enzyme inhibitors. Many of these reports implicate polyacrylonitrile (PAN) as the membrane commonly involved in these reactions. To elucidate potential mechanisms of these anaphylactic reactions, whether dialysis membranes can activate the Hageman factor-dependent (contact) pathways as assessed by the in vitro generation of activated Hageman factor (Hfa), as well as the formation of kallikrein and subsequent bradykinin generation was examined. Both cuprophane (CUP) and PAN membranes were able to activate Hageman factor and convert prekallikrein to kallikrein as measured by an ELISA against kallikrein-C1-inactivator complexes. Subsequently, the active kallikrein was able to cleave bradykinin from its endogenous substrate, high-molecular-weight kininogen. However, it was found that the PAN membrane consistently led to an earlier and significantly higher formation of Hfa and kallikrein when compared with CUP. Importantly, there was also a pronounced but transient generation of bradykinin by the PAN membrane, in contrast to slower bradykinin formation by CUP, with both normal and uremic blood. It was proposed that the early and vigorous bradykinin generation induced by the contact of blood with PAN could explain, in part, the pathogenesis of the reported anaphylactoid reactions.
Sex differences and predictors of objective cough frequency in chronic cough
Authors: A Kelsall, S Decalmer, K McGuinness, A Woodcock, J A Smith
Journal: Thorax (2009)

<h3>Background:</h3> Women are consistently over-represented in specialist cough clinics and known to have a more sensitive cough reflex than men. Whether female sex and other patient characteristics are associated with higher cough rates is not known. A study was conducted to determine the predictors of objective cough frequency in patients presenting to a tertiary referral clinic with chronic cough. <h3>Methods:</h3> 100 subjects (65 women) of mean (SD) age 55.8 (11.0) years and median cough duration 4 years (IQR 2.0–10.0) with unexplained chronic cough completed flow-volume loops (mean (SD) forced expiratory volume in 1 s 103 (15.2)% predicted; forced expiratory flow (FEF<sub>50</sub>) 68.8 (24.1)% predicted), methacholine challenge (42% positive), citric acid cough reflex sensitivity (C5; 0.12 M (IQR 0.06–0.50)) and the Leicester Cough Questionnaire. 24-h ambulatory cough monitoring was performed in 86 subjects; manually counted coughs were quantified as the number of explosive cough sounds per hour. <h3>Results:</h3> Women coughed significantly more than men (geometric mean 16.6 coughs/h (95% CI 13.1 to 21.0) vs 9.4 coughs/h (95% CI 6.4 to 13.9), p = 0.01)). The cough reflex was also more sensitive in women than in men (median logC5 −0.9 M vs −0.6 M, p = 0.002), but cough-related quality of life was similar in women and men (12.0 (3.6) and 12.2 (3.2), respectively, p = 0.76). Linear regression analysis showed that 38.6% of the variation in cough rate was predicted by sex (p = 0.01), logC5 (p&lt;0.001) and age (p = 0.002) but not lung function or bronchial hyper-reactivity. <h3>Conclusions:</h3> Ambulatory objective cough monitoring provides novel insights into factors modulating chronic cough. These findings suggest that effects of sex and age must be taken into account in the study of cough and when designing clinical trials testing novel antitussive agents.