tbuckley/cabot-search huggingface dataset:
Comparison of 2 Family Therapies for Adolescent Anorexia Nervosa
Authors: W. Stewart Agras, James Lock, Harry Brandt, Susan W. Bryson, Elizabeth Dodge, Katherine A. Halmi, Booil Jo, Craig Johnson, Walter Kaye, Denise Wilfley, Blake Woodside
Journal: JAMA Psychiatry (2014)

Anorexia nervosa (AN) is a serious disorder with high rates of morbidity and mortality. Family-based treatment (FBT) is an evidence-based therapy for adolescent AN, but less than half of those who receive this approach recover. Hence, it is important to identify other approaches to prevent the development of the chronic form of AN for which there is no known evidence-based treatment.To compare FBT with systemic family therapy (SyFT) for the treatment of adolescent-onset AN.Research in Anorexia Nervosa (RIAN) is a 2-group (FBT and SyFT) randomized trial conducted between September 2005 and April 2012. Interviewers were blinded to the treatment condition. A total of 564 adolescents receiving care at 6 outpatient clinics experienced in the treatment of AN were screened. Of these, 262 adolescents did not meet the inclusion criteria and 138 declined to participate; hence, 164 adolescents (aged 12-18 years) of both sexes meeting the criteria for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, AN (except for amenorrhea) were enrolled. Three participants were withdrawn from FBT and 7 were withdrawn from SyFT after serious adverse events occurred.Two manualized family therapies with 16 one-hour sessions during 9 months. Family-based therapy focuses on the facilitation of weight gain, whereas SyFT addresses general family processes.The primary outcomes were percentage of ideal body weight (IBW) and remission (≥95% of IBW). The a priori hypothesis was that FBT would result in faster weight gain early in treatment and at the end of treatment (EOT).There were no statistically significant differences between treatment groups for the primary outcome, for eating disorder symptoms or comorbid psychiatric disorders at the EOT or follow-up. Remission rates included FBT, 33.1% at the EOT and 40.7% at follow-up and SyFT, 25.3% and 39.0%, respectively. Family-based therapy led to significantly faster weight gain early in treatment, significantly fewer days in the hospital, and lower treatment costs per patient in remission at the EOT (FBT, $8963; SyFT, $18 005). An exploratory moderator analysis found that SyFT led to greater weight gain than did FBT for participants with more severe obsessive-compulsive symptoms.The findings of this study suggest that FBT is the preferred treatment for adolescent AN because it is not significantly different from SyFT and leads to similar outcomes at a lower cost than SyFT. Adolescents with more severe obsessive-compulsive symptoms may receive more benefits with SyFT.clinicaltrials.gov Identifier NCT00610753.
Editor's Note: Cotreatment with STI-571 Enhances Tumor Necrosis Factor α-related Apoptosis-inducing Ligand (TRAIL or Apo-2L)–induced Apoptosis of Bcr-Abl–positive Human Acute Leukemia Cells
Authors: Ramadevi Nimmanapalli, Mercedes Porosnicu, Diep Nguyen, Elizabeth Worthington, Erica O’Bryan, Charles Perkins, Kapil Bhalla
Journal: Clinical Cancer Research (2019)

The editors are publishing this note to alert readers to concerns about this article (1). Figure 5A and B use the same β-actin control panel. The β-actin control panel in Fig. 3A is similar to lanes 2 through 6 in the β-actin panels in Fig. 5A and B. The original data are no longer available for review, and the authors stand by the conclusions of the article.
Embryonic Expression of the Gax Homeodomain Protein in Cardiac, Smooth, and Skeletal Muscle
Authors: Hal A. Skopicki, Gary E. Lyons, Gina Schatteman, Roy C. Smith, Vicente Andrés, Sabine Schirm, Jeffrey Isner, Kenneth Walsh
Journal: Circulation Research (1997)

Abstract Gax is a homeobox-containing gene that has been detected in adult cardiovascular tissues and exhibits a growth arrest–specific pattern of expression in cultured vascular myocytes. To study the regulation of gax during development, we performed immunohistochemistry and in situ hybridization on mouse embryos. Gax was present in mesodermally and, as with other homeobox genes, neuroectodermally derived tissues. Early mesodermal protein expression was limited to the lateral plate and somitic mesoderm. Gax in the cardiac muscle lineage exhibited a biphasic pattern of expression. Expression was prominent in the heart tube of the earliest cardiomyocytes and remained prominent through the looping stage (day 12.5 post coitum [pc]) but fell below the threshold of detection in atria and ventricles by day 13.5 pc. At day 15.5 pc, Gax protein was again detectable but restricted to cells within the compact layer of the ventricular myocardium. Gax expression was also noted in smooth muscle cells as early as day 9.5 pc. In the skeletal muscle lineage, Gax protein was expressed at the onset of somitogenesis before the expression of the myogenic basic helix-loop-helix and MEF2/RSRF family proteins. Subsequently, it was noted at day 9.5 pc in premyogenic cells migrating into head, trunk, and limb buds. Gax was detected in myotomes, premuscle masses, and mature muscle groups. These data suggest an important developmental role for Gax in all muscle lineages.
Effect of Cholic Acid Feeding on &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N&lt;/italic&gt;-nitrosourea-Induced Colon Tumors and Cell Kinetics in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Bertram I. Cohen
 6, Robert F. Raicht, Eleanor E. Deschner, Makoto Takahashi, Amar N. Sarwal, Eugene Fazzini
Journal: JNCI Journal of the National Cancer Institute (1980)

The tumor-inducing effects of cholic acid feeding were examined in cesarean-derived F344 rats treated with intrarectally administered N-methyl-N-nitrosourea (MNU). The rats were divided into 4 treatment groups. Group 1 received control chow; group 2, control chow and cholic acid (0.2%); group 3, control chow and 8 mg MNU; and group 4, control chow plus 0.2% cholic acid and 8 mg MNU. At 28 weeks, rats in groups 1 and 2 had no tumors. Group 3 had a tumor incidence of 54% (1.1 tumors/animal), whereas rats in group 4 had a tumor incidence of 62% (1.8 tumors/animal). Significantly more tumors were seen in group 4 than in group 3 (modified chi-square, P<0.05). Tumors were primarily adenomas, but invasive adenocarcinomas were also detected. The tumors increased in size from adenomas to invasive carcinomas. Analyses at week 28 revealed a slight increase in fecal neutral sterols in groups 3 and 4 compared with their respective controls (2.17 vs. 1.90 and 2.22 vs. 1.65 mg/g). Conversion of cholesterol to coprostanol was similar in all groups (averaging 65% in groups 1 and 3 and 64% in groups 2 and 4). Total fecal bile acid output was elevated in the cholic acid-fed rats compared with their controls (9.52 vs. 3.68 mg/g feces). The major fecal bile acid in groups 2 and 4 was deoxycholic acid, whereas the amounts of cholic acid were similar in all groups. Deoxycholic acid was presumed to be the primary tumor promoter (or cocarcinogen). Cell kinetics were measured at weeks 5 and 19. At 5 weeks groups 2 and 4 showed enhanced cell proliferation over control values. Cell proliferation was also increased as a result of the MNU-induced damage (group 3). The cumulative effect of MNU and cholic acid feeding increased the numbers of epithelial cells that underwent DNA synthesis. The heightened cell turnover allowed tumors to occur with greater frequency as seen in the cholic acid- plus MNU-treated rats.
Novel Computational Approaches to Polypharmacology as a Means to Define Responses to Individual Drugs
Authors: Lei Xie, Li Xie, Sarah L. Kinnings, Philip E. Bourne
Journal: The Annual Review of Pharmacology and Toxicology (2011)

Polypharmacology, which focuses on designing therapeutics to target multiple receptors, has emerged as a new paradigm in drug discovery. Polypharmacological effects are an attribute of most, if not all, drug molecules. The efficacy and toxicity of drugs, whether designed as single- or multitarget therapeutics, result from complex interactions between pharmacodynamic, pharmacokinetic, genetic, epigenetic, and environmental factors. Ultimately, to predict a drug response phenotype, it is necessary to understand the change in information flow through cellular networks resulting from dynamic drug-target interactions and the impact that this has on the complete biological system. Although such is a future objective, we review recent progress and challenges in computational techniques that enable the prediction and analysis of in vitro and in vivo drug-response phenotypes.
The excess risk of treated end-stage renal disease in blacks in the United States.
Authors: A A Lopes, F K Port, S A James, L Agodoa
Journal: Journal of the American Society of Nephrology (1993)

Analysis of national data from the United States Renal Data System for 1988 revealed an important joint effect of age and race in determining the higher risk of ESRD for blacks as compared with whites. For adults, both hypertension and diabetes made important contributions to the combined effect of age and race. In contrast, glomerulonephritis was not considered to be an important contributor to this joint effect. The combined effect of gender and race was weaker than that of age and race; however, among blacks, differences in the proportions of ESRD attributed to hypertension and diabetes across gender were observed. The age-race joint effect is consistent with the hypothesis that a combined effect of lack of treatment and aging on the process that leads to ESRD may play an important role in the excess risk for ESRD among blacks.
Patients with lung cancer and paraneoplastic Hu syndrome harbor HuD-specific type 2 CD8+ T cells
Authors: Wendy K. Roberts, Ilana J. Deluca, Ashby Thomas, John Fak, Travis Williams, Noreen Buckley, Athanasios G. Dousmanis, Jerome B. Posner, Robert B. Darnell
Journal: Journal of Clinical Investigation (2009)

Paraneoplastic neurologic disorders (PNDs) offer an uncommon opportunity to study human tumor immunity and autoimmunity. In small cell lung cancer (SCLC), expression of the HuD neuronal antigen is thought to lead to immune recognition, suppression of tumor growth, and, in a subset of patients, triggering of the Hu paraneoplastic neurologic syndrome. Antigen-specific CTLs believed to contribute to disease pathophysiology were described 10 years ago in paraneoplastic cerebellar degeneration. Despite parallel efforts, similar cells have not been defined in Hu patients. Here, we have identified HuD-specific T cells in Hu patients and provided an explanation for why their detection has been elusive. Different Hu patients harbored 1 of 2 kinds of HuD-specific CD8+ T cells: classical IFN-γ–producing CTLs or unusual T cells that produced type 2 cytokines, most prominently IL-13 and IL-5, and lacked cytolytic activity. Further, we found evidence that SCLC tumor cells produced type 2 cytokines and that these cytokines trigger naive CD8+ T cells to adopt the atypical type 2 phenotype. These observations demonstrate the presence of an unusual noncytotoxic CD8+ T cell in patients with the Hu paraneoplastic syndrome and suggest that SCLC may evade tumor immune surveillance by skewing tumor antigen–specific T cells to this unusual noncytolytic phenotype.
Intracoronary γ-Radiation Therapy After Angioplasty Inhibits Recurrence in Patients With In-Stent Restenosis
Authors: Ron Waksman, R. Larry White, Rosanna C. Chan, Bill G. Bass, Lisa Geirlach, Gary S. Mintz, Lowell F. Satler, Roxana Mehran, Patrick W. Serruys, Alexandra J. Lansky, Peter Fitzgerald, Balram Bhargava, Kenneth M. Kent, Augusto D. Pichard, Martin B. Leon
Journal: Circulation (2000)

Background —Treatment of in-stent restenosis presents a critical limitation of intracoronary stent implantation. Ionizing radiation has been shown to decrease neointimal formation within stents in animal models and in initial clinical trials. We studied the effects of intracoronary γ-radiation therapy versus placebo on the clinical and angiographic outcomes of patients with in-stent restenosis. Methods and Results —One hundred thirty patients with in-stent restenosis underwent successful coronary intervention and were then blindly randomized to receive either intracoronary γ-radiation with 192 Ir (15 Gy) or placebo. Four independent core laboratories blinded to the treatment protocol analyzed the angiographic and intravascular ultrasound end points of restenosis. Procedural success and in-hospital and 30-day complications were similar among the groups. At 6 months, patients assigned to radiation therapy required less target lesion revascularization and target vessel revascularization (9 [13.8%] and 17 [26.2%], respectively) compared with patients assigned to placebo (41 [63.1%, P =0.0001] and 44 [67.7%, P =0.0001], respectively). Binary angiographic restenosis was lower in the irradiated group (19% versus 58% for placebo, P =0.001). Freedom from major cardiac events was lower in the radiation group (29.2% versus 67.7% for placebo, P &lt;0.001). Conclusions —Intracoronary γ-radiation used as adjunct therapy for patients with in-stent restenosis significantly reduces both angiographic and clinical restenosis.
Mycophenolate Mofetil Does Not Modify the Incidence of Cytomegalovirus (CMV) Disease after Kidney Transplantation but Prevents CMV-Induced Chronic Graft Dysfunction
Authors: MAGALI GIRAL, JEAN MICHEL NGUYEN, PASCAL DAGUIN, MARYVONNE HOURMANT, DIEGO CANTAROVICH, JACQUES DANTAL, GILLES BLANCHO, REGIS JOSIEN, DARIA ANCELET, JEAN PAUL SOULILLOU
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Ganciclovir, which is used to treat cytomegalovirus (CMV) infection, has been shown in rodent models to abolish CMV-mediated chronic cellular damage and endothelial cell proliferation; when associated with mycophenolate mofetil (MMF), it has been shown to increase its anti—herpes virus activity. This study tested the hypothesis that kidney graft recipients who received antirejection prophylaxis with MMF and who were treated with ganciclovir for a declared CMV disease could be protected from chronic graft dysfunction. Investigated was the impact of ganciclovir-treated CMV diseases in consecutive first kidney recipients according to their immunosuppressive therapy. The azathioprine (Aza)-treated group (Aza group) included 319 patients. The MMF-treated group (MMF group) included 126 patients. CMV disease was clinically defined and confirmed by virological proof of CMV infection and was treated for at least 14 d with ganciclovir. Despite having the same incidence (21.6% in the Aza group versus 24.6% in the MMF group) and severity, CMV disease was significantly associated with graft loss independent of acute rejection episodes or other factors when tested in a Cox proportional model in the Aza group only ( P &lt; 10 -4 ). It was shown for the first time that patients whose CMV disease is treated with ganciclovir while they are on MMF therapy are protected from the long-term deleterious consequences of CMV disease on graft survival, independent of acute rejection. It is suggested that the enhanced anti—herpes virus activity of ganciclovir by MMF could contribute to this reported effect, which may represent a significant contribution of MMF efficacy to graft survival.
Cardiac S100A1 Protein Levels Determine Contractile Performance and Propensity Toward Heart Failure After Myocardial Infarction
Authors: Patrick Most, Hanna Seifert, Erhe Gao, Hajime Funakoshi, Mirko Völkers, Jörg Heierhorst, Andrew Remppis, Sven T. Pleger, Brent R. DeGeorge, Andrea D. Eckhart, Arthur M. Feldman, Walter J. Koch
Journal: Circulation (2006)

Diminished cardiac S100A1 protein levels are characteristic of ischemic and dilated human cardiomyopathy. Because S100A1 has recently been identified as a Ca2+-dependent inotropic factor in the heart, this study sought to explore the pathophysiological relevance of S100A1 levels in development and progression of postischemic heart failure (HF).S100A1-transgenic (STG) and S100A1-knockout (SKO) mice were subjected to myocardial infarction (MI) by surgical left anterior descending coronary artery ligation, and survival, cardiac function, and remodeling were compared with nontransgenic littermate control (NLC) and wild-type (WT) animals up to 4 weeks. Although MI size was similar in all groups, infarcted S100A1-deficient hearts (SKO-MI) responded with acute contractile decompensation and accelerated transition to HF, rapid onset of cardiac remodeling with augmented apoptosis, and excessive mortality. NLC/WT-MI mice, displaying a progressive decrease in cardiac S100A1 expression, showed a later onset of cardiac remodeling and progression to HF. Infarcted S100A1-overexpressing hearts (STG-MI), however, showed preserved global contractile performance, abrogated apoptosis, and prevention from cardiac hypertrophy and HF with superior survival compared with NLC/WT-MI and SKO-MI. Both Gq-protein-dependent signaling and protein kinase C activation resulted in decreased cardiac S100A1 mRNA and protein levels, whereas Gs-protein-related signaling exerted opposite effects on cardiac S100A1 abundance. Mechanistically, sarcoplasmic reticulum Ca2+ cycling and beta-adrenergic signaling were severely impaired in SKO-MI myocardium but preserved in STG-MI.Our novel proof-of-concept study provides evidence that downregulation of S100A1 protein critically contributes to contractile dysfunction of the diseased heart, which is potentially responsible for driving the progressive downhill clinical course of patients with HF.
Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis
Authors: Jenny Jongstra-Bilen, Mehran Haidari, Su-Ning Zhu, Mian Chen, Daipayan Guha, Myron I. Cybulsky
Journal: The Journal of Experimental Medicine (2006)

Atherosclerotic lesions develop in regions of arterial curvature and branch points, which are exposed to disturbed blood flow and have unique gene expression patterns. The cellular and molecular basis for atherosclerosis susceptibility in these regions is not completely understood. In the intima of atherosclerosis-predisposed regions of the wild-type C57BL/6 mouse aorta, we quantified increased expression of several proinflammatory genes that have been implicated in atherogenesis, including vascular cell adhesion molecule–1 (VCAM-1) and a relative abundance of dendritic cells, but only occasional T cells. In contrast, very few intimal leukocytes were detected in regions resistant to atherosclerosis; however, abundant macrophages, including T cells, were found throughout the adventitia (Adv). Considerably lower numbers of intimal CD68+ leukocytes were found in inbred atherosclerosis-resistant C3H and BALB/c mouse strains relative to C57BL/6 and 129; however, leukocyte distribution throughout the Adv of all strains was similar. The predominant mechanism for the accumulation of intimal CD68+ cells was continued recruitment of bone marrow–derived blood monocytes, suggestive of low-grade chronic inflammation. Local proliferation of intimal leukocytes was low. Intimal CD68+ leukocytes were reduced in VCAM-1–deficient mice, suggesting that mechanisms of leukocyte accumulation in the intima of normal aorta are analogous to those in atherosclerosis.
Imaging Granzyme B Activity Assesses Immune-Mediated Myocarditis
Authors: Masanori Konishi, S. Sibel Erdem, Ralph Weissleder, Andrew H. Lichtman, Jason R. McCarthy, Peter Libby
Journal: Circulation Research (2015)

Rationale: The development of molecular imaging approaches that assess specific immunopathologic mechanisms can advance the study of myocarditis. Objective: This study validates a novel molecular imaging tool that enables the in vivo visualization of granzyme B activity, a major effector of cytotoxic CD8 + T lymphocytes. Methods and Results: We synthesized and optimized a fluorogenic substrate capable of reporting on granzyme B activity and examined its specificity ex vivo in mice hearts with experimental cytotoxic CD8 + T lymphocyte–mediated myocarditis using fluorescence reflectance imaging, validated by histological examination. In vivo experiments localized granzyme B activity in hearts with acute myocarditis monitored by fluorescent molecular tomography in conjunction with coregistered computed tomography imaging. A model anti-inflammatory intervention (dexamethasone administration) in vivo reduced granzyme B activity (vehicle versus dexamethasone: 504±263 versus 194±77 fluorescence intensities in hearts; P =0.002). Conclusions: Molecular imaging of granzyme B activity can visualize T cell–mediated myocardial injury and monitor the response to an anti-inflammatory intervention.
Mediation of Cytotoxic Immune Responses Against Human Tumor-Associated Antigens by Xenogeneic Immune RNA 2
Authors: David H. Kern, Dieter Fritze, Carol R. Drogemuller, Yosef H. Pilch
Journal: JNCI Journal of the National Cancer Institute (1976)

Allogeneic immune RNA (I-RNA), extracted from the peripheral blood lymphocytes of patients putatively cured of cancer, mediated cytotoxic immune reactions that apparently were directed specifically against human tumor-associated antigens. I-RNA was extracted from the peripheral blood lymphocytes of patients with various types of cancer. Patients selected had not been previously sensitized to HL-A or other normal transplantation antigens or to blood group antigens. Normal human peripheral blood lymphocytes were incubated with these allogeneic I-RNA preparations and tested for cytotoxicity against human target cells in vitro. Allogeneic I-RNA mediated cytotoxic immune reactions only against tumor target cells of the same histologic type as the I-RNA donor. I-RNA's extracted from peripheral blood lymphocytes of melanoma patients mediated cytotoxic immune reactions only against melanoma cells. Similarly, only I-RNA's extracted from the lymphocytes of patients with colon cancer mediated cytotoxic immune reactions against colon carcinoma cells, and only I-RNA's from the lymphocytes of breast cancer patients mediated immune reactions against breast cancer target cells. Allogeneic I-RNA extracted from peripheral blood lymphocytes of cancer patients possibly mediated specific cytotoxic immune reactions that were directed against common tumor-associated antigens shared by human tumors of similar histologic type.
The Impact of Minimally Invasive Surgical Techniques
Authors: Ara Darzi, Yaron Munz
Journal: Annual Review of Medicine (2004)

The use of minimally invasive techniques (MIT) in patient care is well documented in ancient history; however, it was not until the 1990s that advancements in technology enabled surgeons to realize the true potential of this approach. The minimally invasive approach has revolutionized surgical care, significantly reducing postoperative pain, recovery time, and hospital stays with marked improvements in cosmetic outcome and overall cost-effectiveness. It is now used around the world and in all major fields of surgery, compelling changes in training programs in order to assure quality control and patient safety. The bond between surgeons practicing minimally invasive surgery (MIS) and the high-tech industry is of utmost importance to future developments. Surgical robotic systems represent the most technologically advanced product of this collaboration, and their potential application in MIS shows much promise. As technology advances, additional developments in MIT are likely.