tbuckley/cabot-search huggingface dataset:
Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis progression in pubertal lupus patients with higher C reactive protein
Authors: Stacy P Ardoin, Laura Eve Schanberg, Christy I Sandborg, Huiman X Barnhart, Greg W Evans, Eric Yow, Kelly L Mieszkalski, Norman T Ilowite, Anne Eberhard, Lisa F Imundo, Yuki Kimura, Deborah Levy, Emily von Scheven, Earl Silverman, Suzanne L Bowyer, L Punaro, Nora G Singer, David D Sherry, Deborah K McCurdy, Marissa Klein-Gitelman, Carol Wallace, Richard M Silver, Linda Wagner-Weiner, Gloria C Higgins, Hermine I Brunner, Lawrence Jung, Jennifer B Soep, Ann M Reed, Susan D Thompson
Journal: Annals of the Rheumatic Diseases (2013)

Objective Participants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy. Methods Subgroups were prespecified and defined by age (&gt; or ≤15.5 years), systemic lupus erythematosus (SLE) duration (&gt; or ≤24 months), pubertal status (Tanner score ≥4 as post-pubertal or &lt;4 as pre-pubertal), low density lipoprotein cholesterol (LDL) (≥ or &lt;110 mg/dl) and high-sensitivity C reactive protein (hsCRP) (≥ or &lt;1.5 mg/l). A combined subgroup (post-pubertal and hsCRP≥1.5 mg/l) was compared to all others. Longitudinal linear mixed-effects models were developed using 12 CIMT and other secondary APPLE outcomes (lipids, hsCRP, disease activity and damage, and quality of life). Three way interaction effects were assessed for models. Results Significant interaction effects with trends of less CIMT progression in atorvastatin-treated participants were observed in pubertal (3 CIMT segments), high hsCRP (2 CIMT segments), and the combined high hsCRP and pubertal group (5 CIMT segments). No significant treatment effect trends were observed across subgroups defined by age, SLE duration, LDL for CIMT or other outcome measures. Conclusions Pubertal status and higher hsCRP were linked to lower CIMT progression in atorvastatin-treated subjects, with most consistent decreases in CIMT progression in the combined pubertal and high hsCRP group. While secondary analyses must be interpreted cautiously, results suggest further research is needed to determine whether pubertal lupus patients with high CRP benefit from statin therapy. ClinicalTrials.gov identifier: NCT00065806.
Pathogenesis of secondary hypertrophic osteoarthropathy: a hypothesis
Authors: L Doyle
Journal: European Respiratory Journal (1989)

Wide ranges both in the location and the pathological state of the primary disease associated with hypertrophic osteoarthropathy (HO) have been noted. The combined distribution of the glossopharyngeal and vagus nerves appears to coincide with the range of locations of the primary disease associated with HO. These two nerves are believed to contribute to the innervation of the blood vessels in this same area. This hypothesis states that: i) some of this innervation is part of a blood volume control system; and ii) by an inappropriate stimulation of this system, as a result of blood-flow in an anomalous vascular rearrangement lying close to the primary disease associated with HO, a cerebral salt centre is stimulated to retain extra-cellular sodium. A secondary atrial natriuretic peptide over-secretion ensues and a "near steady-state" is established, with the presence of excess fluid and dilated vessels in all four limbs. Thus, the pathogenesis of HO and the distribution of an extra-renal volume control system are reciprocal facets of the same question.
Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity.
Authors: A Moretta, G Pantaleo, L Moretta, J C Cerottini, M C Mingari
Journal: The Journal of Experimental Medicine (1983)

In an attempt to determine the clonogenic properties of human peripheral blood T cells, we have developed a limiting dilution microculture system using phytohemagglutinin (PHA) as T cell activator and supernatant from PHA-stimulated spleen cultures as a source of T cell growth factors. The frequencies of cells capable of extensive proliferation under these culture conditions were 0.52-0.73, 0.98-1.11, and less than 0.02 in peripheral blood mononuclear, E-rosette-positive, and E-rosette-negative cell populations, respectively. The clonogenic potential of virtually all T cells was confirmed in experiments using single cells isolated by micromanipulation. Clone size ranged between 5 and 30 X 10(4) cells on day 14 of culture. The same microculture system was used to determine the precursor frequency of all cytolytic T lymphocytes (CTL-P). As assessed by a lectin-dependent 51Cr release assay, the CTL-P frequency in purified T cell populations ranged between 0.30 and 0.34. In comparison, the precursor frequency of T cells capable of lysing K562 target cells was ranging between 0.14 and 0.16. Parallel analysis of individual clonal cultures for both lytic activities showed that 50% of the clones exhibiting lectin-dependent lysis were also active against K562 target cells. All of the proliferating clones expressed HLA-DR antigens, although to a varying degree as assessed by flow cytofluorometry. Given the high cloning efficiency of this culture system, it appears now possible to determine the precursor frequencies of the various classes of functional cells in T cell populations.
The role of TGF-β signaling in myocardial infarction and cardiac remodeling
Authors: M BUJAK, N FRANGOGIANNIS
Journal: Cardiovascular Research (2006)

Transforming Growth Factor (TGF)-beta is markedly induced and rapidly activated in the infarcted myocardium. However, understanding of the exact role of TGF-beta signaling in the infarcted and remodeling heart has been hampered by the complex and unusual biology of TGF-beta activation and by the diversity of its effects eliciting multiple, and often opposing cellular responses. Experimental studies suggest that TGF-beta signaling may be crucial for repression of inflammatory gene synthesis in healing infarcts mediating resolution of the inflammatory infiltrate. In addition, TGF-beta may play an important role in modulating fibroblast phenotype and gene expression, promoting extracellular matrix deposition in the infarct by upregulating collagen and fibronectin synthesis and by decreasing matrix degradation through induction of protease inhibitors. TGF-beta is also a key mediator in the pathogenesis of hypertrophic and dilative ventricular remodeling by stimulating cardiomyocyte growth and by inducing interstitial fibrosis. In this review we summarize the current knowledge on the role of TGF-beta in infarct healing and cardiac remodeling.
Epidemiology of injuries in typical Scandinavian team sports.
Authors: U. Jørgensen
Journal: British Journal of Sports Medicine (1984)

An investigation by questionnaire was undertaken in a group of 480 football players and 288 handball players (768 players). Of these 803 were injured, giving a player incidence of 4.1 injury/1000 football hours and 8.3 injury/1000 handball hours. The lower extremities were involved in 82% of the football injuries, whereas handball injuries were evenly distributed on both upper and lower extremities. The football injury prevalence was 0.36 per player, the handball injury prevalence 0.71 per player. Medical attention was given to 62% of the injured footballers and 47% of the injured handballers. Based on the injury pattern, some modifications to the rules and equipment in the two sports is suggested: The "boot-type" footwear should be tried out, and the soles in both games should correspond to the different playing surfaces that may be encountered. Stricter enforcement of the rules, and the use of a maximum size playing ground in both sports. Last, but not least a modification of the football rules concerning substitution is a must.
Viral interleukin 10 (IL-10), the human herpes virus 4 cellular IL-10 homologue, induces local anergy to allogeneic and syngeneic tumors.
Authors: T Suzuki, H Tahara, S Narula, K W Moore, P D Robbins, M T Lotze
Journal: The Journal of Experimental Medicine (1995)

After the cloning of murine cytokine synthesis inhibitory factor, it was recognized that a homologous open reading frame was encoded within the Epstein-Barr virus (human herpes virus 4). This viral protein has now been termed viral interleukin 10 (vIL-10) to reflect its protein sequence homology to "cellular" IL-10 (cIL-10, either murine or human IL-10). It is now widely accepted that vIL-10 shares many functions with cIL-10, principally, the ability to enhance survival of newly infected B cells and to diminish the production of IFN-gamma and IL-2 during ongoing immune reactions. The immunomodulatory effect of locally secreted vIL-10 and murine IL-10 (mIL-10) was examined in tumor models using CL8-1 (a BL6 melanoma cell line transfected with the H-2Kb class I gene) in syngeneic animals. Although parental BL6 tumor cells grow in immunocompetent syngeneic hosts, CL8-1 are rejected. To achieve local secretion of vIL-10, we generated vIL-10 retroviral vectors. While nontransduced CL8-1 cells (1 x 10(4)) failed to grow when injected intradermally in C57BL/6 mice, CL8-1 cells (1 x 10(4)) transduced with vIL-10 formed palpable tumors and eventually killed 80% of injected animals. Suppression of tumor rejection was also noted when CL8-1 tumors with or without vIL-10 transfection were admixed with syngeneic vIL-10-transfected fibroblasts and inoculated. Since the in vitro proliferation of the tumor was not altered after transduction with the vIL-10 gene and injection of vIL-10-transduced CL8-1 does not affect the rejection of nontransduced CL8-1 inoculated at a distant site, local vIL-10 secretion appears to suppress the process of immune rejection of the target cells in a dose-dependent manner. Similar results were observed for the H-2b MCA105 sarcoma tumor model in allogeneic BALB/c mice (H-2d). Although all animals that received nontransfected MCA105 rapidly rejected these tumors, MCA105 sarcomas transfected with vIL-10 remained palpable for up to 37 d. The local immunosuppressive effect of gene-delivered vIL-10 could be neutralized by anti-human IL-10 monoclonal antibody or could be reversed by the systemic administration of IL-2 or IL-12. In marked contrast, mIL-10 transfection of CL8-1 significantly suppressed tumor growth and frequently led to the rejection of tumor. Similar results were obtained for the murine tumor cell lines MCA102.(ABSTRACT TRUNCATED AT 400 WORDS)
Agencies collaborate to tackle world's biggest killers
Authors: A. O'Dowd
Journal: BMJ (2009)

Six of the world’s leading health agencies have formed a groundbreaking alliance in an attempt to tackle diseases such as cancers, cardiovascular diseases, and type 2 diabetes.

The newly formed Global Alliance for Chronic Diseases is a collaboration between the United Kingdom’s Medical Research Council; Australia’s National Health Medical Research Council; the Canadian Institutes of Health Research; China’s Ministry of Health in association with the Chinese Academy of Medical Sciences; and the US National Institutes of Health’s National Heart, Lung, and Blood Institute, and the Fogarty International Center.

The sixth organisation that will be invited to join the alliance is the Indian Council of …
Clinical Applications of Metabolomics in Oncology: A Review
Authors: Jennifer L. Spratlin, Natalie J. Serkova, S. Gail Eckhardt
Journal: Clinical Cancer Research (2009)

Abstract Metabolomics, an omic science in systems biology, is the global quantitative assessment of endogenous metabolites within a biological system. Either individually or grouped as a metabolomic profile, detection of metabolites is carried out in cells, tissues, or biofluids by either nuclear magnetic resonance spectroscopy or mass spectrometry. There is potential for the metabolome to have a multitude of uses in oncology, including the early detection and diagnosis of cancer and as both a predictive and pharmacodynamic marker of drug effect. Despite this, there is lack of knowledge in the oncology community regarding metabolomics and confusion about its methodologic processes, technical challenges, and clinical applications. Metabolomics, when used as a translational research tool, can provide a link between the laboratory and clinic, particularly because metabolic and molecular imaging technologies, such as positron emission tomography and magnetic resonance spectroscopic imaging, enable the discrimination of metabolic markers noninvasively in vivo. Here, we review the current and potential applications of metabolomics, focusing on its use as a biomarker for cancer diagnosis, prognosis, and therapeutic evaluation.
A 20-Month, Double-Blind, Maintenance Trial of Lithium Versus Divalproex in Rapid-Cycling Bipolar Disorder
Authors: Joseph R. Calabrese, Melvin D. Shelton, Daniel J. Rapport, Eric A. Youngstrom, Kelly Jackson, Sarah Bilali, Stephen J. Ganocy, Robert L. Findling
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors tested the hypothesis that divalproex would be more effective than lithium in the long-term management of patients with recently stabilized rapid-cycling bipolar disorder. METHOD: A 20-month, double-blind, parallel-group comparison was carried out in recently hypomanic/manic patients who had experienced a persistent bimodal response to combined treatment with lithium and divalproex. Sixty patients were randomly assigned to lithium or divalproex monotherapy in a balanced design after stratification for illness type (bipolar I versus bipolar II disorder). RESULTS: Of the 254 patients enrolled in the open-label acute stabilization phase, 76% discontinued the study prematurely (poor adherence: 28%; nonresponse: 26% [of whom 74% remained depressed and 26% remained in a hypomanic/manic/mixed episode], intolerable side effects: 19%). Of the 60 patients (24%) randomly assigned to double-blind maintenance monotherapy, 53% relapsed (59% into depression and 41% into a hypomanic/manic/mixed episode), 22% completed the study, 10% had intolerable side effects, and 10% were poorly adherent. The rates of relapse into any mood episode for those given lithium versus divalproex were 56% and 50%, respectively; the rates were 34% and 29% for a depressive relapse and 19% and 22% for a hypomania/mania relapse. There were no significant differences in time to relapse. The proportion discontinuing prematurely because of side effects was 16% for lithium and 4% for divalproex. CONCLUSIONS: The hypothesis that divalproex is more effective than lithium in the long-term management of rapid-cycling bipolar disorder is not supported by these data. Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid-cycling bipolar disorder.
Schedule-Dependent Cytotoxicity of 5-Fluorouracil in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G Santelli, F Valeriote
Journal: JNCI Journal of the National Cancer Institute (1986)

The cytotoxic effect of 5-fluorouracil (FUra) given as a 24-hour infusion against both AKR and L1210 leukemias was quantitated by spleen colony assays. The antitumor effect was enhanced in AKR leukemia but was reduced in L1210 leukemia when FUra was given as a 24-hour infusion compared to when the drug was given as an iv bolus injection. No difference in cytotoxicity was noted for these two schedules against normal hematopoietic stem cells in either AKR or (BALB/c X DBA/2)F1 mice. The pharmacokinetics of FUra given as an infusion was similar in the mice bearing these two transplantable leukemias, which ruled out the possibility that the pharmacokinetics of FUra was the cause of the difference observed. Finally, correlation was good between the spleen colony assays and the therapeutic effect defined by life-span assays for both leukemias.
The Human Placental Lactogen Genes: Structure, Function, Evolution and Transcriptional Regulation
Authors: WILLIAM H. WALKER, SUSAN L. FITZPATRICK, HUGO A. BARRERA-SALDAÑA, DIANA RESÉNDEZ-PÉREZ, GRADY F. SAUNDERS
Journal: Endocrine Reviews (1991)

THE placenta is an important source of a diverse group of hormones, cytokines, and growth factors necessary for continuation of pregnancy. Due to its continued growth and differentiation during gestation, the placenta represents a unique organ for the study of hormonal genes during development. The production of one hormone in particular, placental lactogen (PL), also called chorionic somatomammotropin (CS), reflects the development of the placenta as blood PL levels rise throughout pregnancy and reach a peak at term. Human PL (hPL) is a member of a closely related gene family that includes human GH (hGH) and human PRL (hPRL). Although these genes are highly similar and have evolved from a common precursor, they have dramatically different physiological functions and regulatory mechanisms. Recently, advances have been made in understanding the regulation of hPL production and its physiological significance. In this review we discuss the various physiological actions of hPL during pregnancy, the evolution and structure of hPL genes, and the tissue-specific regulation of hPL gene expression.
Evidence from a House Finch (Haemorhous mexicanus) Spleen Transcriptome for Adaptive Evolution and Biased Gene Conversion in Passerine Birds
Authors: Niclas Backström, Qu Zhang, Scott V. Edwards
Journal: Molecular Biology and Evolution (2013)

Identifying genes influenced by natural selection can provide information about lineage-specific adaptations, and transcriptomes generated by next-generation sequencing are a useful resource for identifying such genes. Here, we utilize a spleen transcriptome for the house finch (Haemorhous mexicanus), an emerging model for sexual selection and disease ecology, together with previously sequenced avian genomes (chicken, turkey, and zebra finch), to investigate lineage-specific adaptations within birds. An analysis of 4,398 orthologous genes revealed a significantly higher ratio of nonsynonymous to synonymous substitutions and significantly higher GC content in passerines than in galliforms, an observation deviating from strictly neutral expectations but consistent with an effect of biased gene conversion on the evolutionary rate in passerines. These data also showed that genes exhibiting signs of positive selection and fast evolution in passerines have functional roles related to fat metabolism, neurodevelopment, and ion binding.
EMP1, a novel poor prognostic factor in pediatric leukemia regulates prednisolone resistance, cell proliferation, migration and adhesion
Authors: I M Ariës, I S Jerchel, R E S R van den Dungen, L C J van den Berk, J M Boer, M A Horstmann, G Escherich, R Pieters, M L den Boer
Journal: Leukemia (2014)
A Phase I and Pharmacodynamic Study of Fludarabine, Carboplatin, and Topotecan in Patients With Relapsed, Refractory, or High-Risk Acute Leukemia
Authors: Brenda W. Cooper, Gareth J. Veal, Tomas Radivoyevitch, Michael J. Tilby, Howard J. Meyerson, Hillard M. Lazarus, Omer N. Koc, Richard J. Creger, Graham Pearson, Geoff M. Nowell, David Gosky, Stephen T. Ingalls, Charles L. Hoppel, Stanton L. Gerson
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A novel regimen designed to maximize antileukemia activity of carboplatin through inhibiting repair of platinum-DNA adducts was conducted in poor prognosis, acute leukemia patients. Experimental Design: Patients received fludarabine (10 to 15 mg/m2 × 5 days), carboplatin (area under the curve 10 to 12 by continuous infusion over 5 days), followed by escalated doses of topotecan infused over 72 hours (fludarabine, carboplatin, topotecan regimen). Twenty-eight patients had acute myelogenous leukemia (7 untreated secondary acute myelogenous leukemia, 11 in first relapse, and 10 in second relapse or refractory), 1 patient had refractory/relapsed acute lymphoblastic leukemia, and 2 patients had untreated chronic myelogenous leukemia blast crisis. Six patients had failed an autologous stem cell transplant. Patients ranged from 19 to 76 (median 54) years. Measurement of platinum-DNA adducts were done in serial bone marrow specimens. Results: Fifteen of 31 patients achieved bone marrow aplasia. Clinical responses included 2 complete response, 4 complete response with persistent thrombocytopenia, and 2 partial response. Prolonged myelosuppression was observed with median time to blood neutrophils ≥200/μl of 28 (0 to 43) days and time to platelets ≥20,000/μl (untransfused) of 40 (24 to 120) days. Grade 3 or greater infections occurred in all of the patients, and there were 2 infection-related deaths. The nonhematologic toxicity profile was acceptable. Five patients subsequently received allografts without early transplant-related mortality. Maximum tolerated dose of fludarabine, carboplatin, topotecan regimen was fludarabine 15 mg/m2 × 5, carboplatin area under the curve 12, and topotecan 2.55 mg/m2 over 72 hours. An increase in bone marrow, platinum-DNA adduct formation between the end of carboplatin infusion and 48 hours after the infusion correlated with bone marrow response. Conclusions: Fludarabine, carboplatin, topotecan regimen is a promising treatment based on potential pharmacodynamic interactions, which merits additional study in poor prognosis, acute leukemia patients.
Predictive Value of Cardiac Autonomic Neuropathy in Diabetic Patients With or Without Silent Myocardial Ischemia
Authors: Paul Valensi, Régis-Nessim Sachs, Boubakeur Harfouche, Boris Lormeau, Jacques Paries, Emmanuel Cosson, Frédéric Paycha, Marc Leutenegger, Jean-Raymond Attali
Journal: Diabetes Care (2001)

The aim of this study was to determine the predictive value of silent myocardial ischemia (SMI) and cardiac autonomic neuropathy (CAN) in asymptomatic diabetic patients.We recruited 120 diabetic patients with no history of myocardial infarction or angina, a normal 12-lead electrocardiogram (ECG), and two or more additional risk factors. SMI assessment was carried out by means of an ECG stress test, a thallium-201 myocardial scintigraphy with dipyridamole, and 48-h ECG monitoring. CAN was searched for by standardized tests evaluating heart rate variations. Accurate follow-up information for 3-7 years (mean 4.5) was obtained in 107 patients.There was evidence of SMI in 33 patients (30.7%). CAN was detected in 33 of the 75 patients (38.9%) who were tested, and a major cardiac event occurred in 11 of them. Among these 75 patients, the proportion of major cardiac events in the SMI+ patients was not significantly higher than that in the SMI- patients (6 of 25 vs. 5 of 50 patients), whereas it was significantly higher in the CAN+ patients than in the CAN- patients (8 of 33 vs. 3 of 42 patients; P = 0.04), with a relative risk of 4.16 (95% CI 1.01-17.19) and was the highest in the patients with both SMI and CAN (5 of 10 patients). After adjusting for SMI, there was a significant association between CAN and major cardiac events (P = 0.04).In asymptomatic diabetic patients, CAN appears to be a better predictor of major cardiac events than SMI. The risk linked to CAN appears to be independent of SMI and is the highest when CAN is associated with SMI.
Pulmonary Complications of Solid Organ and Hematopoietic Stem Cell Transplantation
Authors: Robert M. Kotloff, Vivek N. Ahya, Stephen W. Crawford
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

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