tbuckley/cabot-search huggingface dataset:
Second and Subsequent Recurrences of Osteosarcoma: Presentation, Treatment, and Outcomes of 249 Consecutive Cooperative Osteosarcoma Study Group Patients
Authors: Stefan S. Bielack, Beate Kempf-Bielack, Detlev Branscheid, Dorothe Carrle, Godehard Friedel, Knut Helmke, Matthias Kevric, Gernot Jundt, Thomas Kühne, Rainer Maas, Rudolf Schwarz, Andreas Zoubek, Heribert Jürgens
Journal: Journal of Clinical Oncology (2008)

Purpose To evaluate patient and tumor characteristics, treatment, and outcomes in a large cohort of unselected patients with second and subsequent recurrences of osteosarcoma. Patients and Methods Two hundred forty-nine consecutive patients who had originally received combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group protocols and went on to develop a total of 409 second and subsequent osteosarcoma recurrences were analyzed for patient-, tumor-, and treatment-related factors and outcomes. Results Five-year overall and event-free survival rates were 16% and 9% for 249 second, 14% and 0% for 93 third, 13% and 6% for 38 fourth, and 18% and 0% for 14 fifth recurrences, respectively. The proportion of recurrences confined to the lungs decreased and the proportion of those with chest wall involvement increased with increasing numbers of recurrences. The duration of relapse-free intervals and the number of lesions at recurrence correlated with outcomes. While only one of 205 patients with rerecurrence survived past 5 years without surgical remission, 5-year overall and event-free survival rates were 32% and 18% for 119 second, 26% and 0% for 45 third, 28% and 13% for 20 fourth, and 53% and 0% for five fifth recurrences, respectively, in which a renewed surgical remission was achieved. The use of chemotherapy correlated with longer survival in patients without surgical remissions. Conclusion To our knowledge, this is the first report of survival estimates derived from large cohorts of unselected patients with second and subsequent osteosarcoma recurrences. It confirms the overwhelming importance of surgical clearance. Prognostic indicators after rerecurrences resemble those known from first recurrence. The exact role of re-treatment with chemotherapy, particularly in the adjuvant situation, remains to be defined.
Prevalence of Autism Spectrum Disorders in a Total Population Sample
Authors: Young Shin Kim, Bennett L. Leventhal, Yun-Joo Koh, Eric Fombonne, Eugene Laska, Eun-Chung Lim, Keun-Ah Cheon, Soo-Jeong Kim, Young-Key Kim, HyunKyung Lee, Dong-Ho Song, Roy Richard Grinker
Journal: American Journal of Psychiatry (2011)

Experts disagree about the causes and significance of the recent increases in the prevalence of autism spectrum disorders (ASDs). Limited data on population base rates contribute to this uncertainty. Using a population-based sample, the authors sought to estimate the prevalence and describe the clinical characteristics of ASDs in school-age children.The target population was all 7- to 12-year-old children (N=55,266) in a South Korean community; the study used a high-probability group from special education schools and a disability registry and a low-probability, general-population sample from regular schools. To identify cases, the authors used the Autism Spectrum Screening Questionnaire for systematic, multi-informant screening. Parents of children who screened positive were offered comprehensive assessments using standardized diagnostic procedures.The prevalence of ASDs was estimated to be 2.64% (95% CI=1.91-3.37), with 1.89% (95% CI=1.43-2.36) in the general-population sample and 0.75% (95% CI=0.58-0.93) in the high-probability group. ASD characteristics differed between the two groups: the male-to-female ratios were 2.5:1 and 5.1:1 in the general population sample and high-probability group, respectively, and the ratios of autistic disorders to other ASD subtypes were 1:2.6 and 2.6:1, respectively; 12% in the general-population sample had superior IQs, compared with 7% in the high-probability group; and 16% in the general-population sample had intellectual disability, compared with 59% in the high-probability group.Two-thirds of ASD cases in the overall sample were in the mainstream school population, undiagnosed and untreated. These findings suggest that rigorous screening and comprehensive population coverage are necessary to produce more accurate ASD prevalence estimates and underscore the need for better detection, assessment, and services.
Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus.
Authors: A Vaag, J E Henriksen, S Madsbad, N Holm, H Beck-Nielsen
Journal: Journal of Clinical Investigation (1995)

12 identical twin pairs discordant for non-insulin-dependent diabetes mellitus (NIDDM) were studied for insulin sensitivity (euglycemic insulin clamp, 40 mU/m2 per min), hepatic glucose production (HGP, [3-3H]glucose infusion), and insulin secretion (oral glucose tolerance test and hyperglycemic [12 mM] clamp, including glucagon administration). Five of the nondiabetic twins had normal and seven had impaired glucose tolerance. 13 matched, healthy subjects without a family history of diabetes were included as control subjects. The NIDDM twins were more obese compared with their non-diabetic co-twins. The nondiabetic twins were insulin resistant and had a delayed insulin and C-peptide response during oral glucose tolerance tests compared with controls. Furthermore, the nondiabetic twins had a decreased first-phase insulin response and a decreased maximal insulin secretion capacity during hyperglycemic clamping and intravenous glucagon administration. Nondiabetic twins and controls had similar rates of HGP. Compared with both nondiabetic twins and controls, the NIDDM twins had an elevated basal rate of HGP, a further decreased insulin sensitivity, and a further impaired insulin secretion pattern as determined by all tests. In conclusion, defects of both in vivo insulin secretion and insulin action are present in non- and possibly prediabetic twins who possess the necessary NIDDM susceptibility genes. However, all defects of both insulin secretion and glucose metabolism are expressed quantitatively more severely in their identical co-twins with overt NIDDM.
Tyrosine Kinase Etk/BMX Is Up-regulated in Human Prostate Cancer and Its Overexpression Induces Prostate Intraepithelial Neoplasia in Mouse
Authors: Bojie Dai, Oekyung Kim, Yingqiu Xie, Zhiyong Guo, Kexin Xu, Bin Wang, Xiangtian Kong, Jonathan Melamed, Hegang Chen, Charles J. Bieberich, Alexander D. Borowsky, Hsing-Jien Kung, Guo Wei, Michael C. Ostrowski, Angela Brodie, Yun Qiu
Journal: Cancer Research (2006)

Abstract The nonreceptor tyrosine kinase Etk/BMX was originally identified from the human prostate xenograft CWR22. Here, we report that Etk is up-regulated in human prostate tumor specimens surveyed. Knocking down Etk expression by a specific small interfering RNA (siRNA) in prostate cancer cells attenuates cell proliferation, suggesting an essential role of Etk for prostate cancer cell survival and growth. Targeted expression of Etk in mouse prostate epithelium results in pathologic changes resembling human prostatic intraepithelial neoplasia, indicating that up-regulation of Etk may contribute to prostate cancer development. A marked increase of luminal epithelial cell proliferation was observed in the Etk transgenic prostate, which may be attributed in part to the elevated activity of Akt and signal transducers and activators of transcription 3 (STAT3). More interestingly, the expression level of acetyltransferase cyclic AMP–responsive element binding protein–binding protein (CBP) is also increased in the Etk transgenic prostate as well as in a prostate cancer cell line overexpressing Etk, concomitant with elevated histone 3 acetylation at lysine 18 (H3K18Ac). Down-modulation of Etk expression by a specific siRNA leads to a decrease of H3 acetylation in prostate cancer cell lines. Our data suggest that Etk may also modulate chromatin remodeling by regulating the activity of acetyltransferases, such as CBP. Given that Etk may exert its effects in prostate through modulation of multiple signaling pathways altered in human prostate cancer, the Etk transgenic mouse model may be a useful tool for studying the functions of Etk and identification of new molecular markers and drug targets relevant to human diseases. (Cancer Res 2006; 66(16): 8058-64)
Water and Electrolyte Content of Normal and Hypertensive Arteries in Dogs
Authors: ALLAN W. JONES, ERIC O. FEIGL, LYSLE H. PETERSON
Journal: Circulation Research (1964)

This study was designed to establish values for the water and electrolyte content along the arterial tree in the dog under normal conditions and to determine how the normal electrolyte pattern was altered in renal hypertension. Determinations of vessel wall water, potassium, sodium, and chloride contents have shown that the water and electrolyte contents from the various sites along the arterial tree differ significantly from each other. Total water and potassium contents decrease progressively from the ascending aorta to the femoral and carotid sites, while the sodium and chloride contents showed the opposite trend. These differences were significant statistically. These trends may not persist along the entire vascular tree to very small arteries, as indicated by analysis of mesenteric arterial samples. Studies of vessel wall inulin space supported the view that these differences result from the relative distribution of cellular and noncellular material; thus the proximal aorta contains a relatively greater proportion of cellular (smooth muscle) material than more distal sites such as the femoral and carotid arteries. A review of the literature further supports these findings. In experimentally induced renal hypertension the same trends persist along the aorta, but the total water and sodium contents are significantly elevated at all sites.
Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study
Authors: Isabelle Ray-Coquard, Jean-Yves Blay, Antoine Italiano, Axel Le Cesne, Nicolas Penel, Jianguo Zhi, Florian Heil, Ruediger Rueger, Bradford Graves, Meichun Ding, David Geho, Steven A Middleton, Lyubomir T Vassilev, Gwen L Nichols, Binh Nguyen Bui
Journal: The Lancet Oncology (2012)
Interaction of Heat Shock Proteins with Peptides and Antigen Presenting Cells: Chaperoning of the Innate and Adaptive Immune Responses
Authors: Pramod Srivastava
Journal: Annual Review of Immunology (2002)

Heat shock proteins are abundant soluble intracellular proteins, present in all cells. Members of the heat shock protein family bind peptides including antigenic peptides generated within cells. Heat shock proteins also interact with antigen presenting cells through CD91 and other receptors, eliciting a cascade of events including re-presentation of heat shock protein-chaperoned peptides by MHC, translocation of NFκB into the nuclei and maturation of dendritic cells. These consequences point to a key role of heat shock proteins in fundamental immunological phenomena such as activation of antigen presenting cells, indirect presentation (or cross-priming), and chaperoning of peptides during antigen presentation. Heat shock proteins appear to have been involved in innate immune responses since the emergence of phagocytes in early multicellular organisms and to have been commandeered for adaptive immune responses with the advent of specificity. These properties of heat shock proteins also allow them to be used for immunotherapy of cancers and infections in novel ways.
A Combination Hybrid-Based Vaccination/Adoptive Cellular Therapy to Prevent Tumor Growth by Involvement of T Cells
Authors: Rajkumar Savai, Ralph Theo Schermuly, Soni Savai Pullamsetti, Michael Schneider, Susanne Greschus, Hossein Ardeschir Ghofrani, Horst Traupe, Friedrich Grimminger, Gamal-Andre Banat
Journal: Cancer Research (2007)

Cancer immunotherapy with dendritic cell-tumor cell fusion hybrids induces polyclonal stimulation against a variety of tumor antigens, including unknown antigens. Hybrid cells can prime CTLs, which subsequently develop antitumor responses. The aim of this study was to enhance the known antitumor effect of hybrid vaccination (HC-Vacc) and hybrid-primed adoptive T-cell therapy (HC-ACT) using the poorly immunogenic Lewis lung carcinoma (LLC1) model. The strategy used was a combination of a double HC-Vacc alternating with HC-ACT (HC-Vacc/ACT). Using flat-panel volumetric computer tomography and immunohistochemistry, we showed a significant retardation of tumor growth (85%). In addition, a significant delay in tumor development, a reduction in the number of pulmonary metastases, and increased survival times were observed. Furthermore, the tumors displayed significant morphologic changes and increased apoptosis, as shown by up-regulation of gene expression of the proapoptotic markers Fas, caspase-8, and caspase-3. The residual tumor masses seen in the HC-Vacc/ACT-treated mice were infiltrated with CD4+ and CD8+ lymphocytes and showed elevated IFNgamma expression. Moreover, splenic enlargement observed in HC-Vacc/ACT-treated mice reflected the increased functionality of T cells, as also indicated by increased expression of markers for CTL activation, differentiation, and proliferation (Cd28, Icosl, Tnfrsf13, and Tnfsf14). Our findings indicate that the combination therapy of dendritic cell-tumor cell HC-Vacc/ACT is a very effective and a promising immunotherapeutic regimen against poorly immunogenic carcinomas.
FORMALDEHYDE-INDUCED FLUORESCENCE OF INTRANUCLEAR BODIES IN MELANOMA CELLS*
Authors: B. EHINGER, B. FALCK, S. JACOBSSON, H. RORSMAN
Journal: British Journal of Dermatology (1969)

SUMMARY.— Imprints of 5 human melanomas were treated with formaldehyde and studied by fluorescence microscopy. Granular fluorescence was seen in the cytoplasm, and, in two of the melanomas, also large intranuclear fluorescent bodies. Microspectrofluorometry showed that the fluorescence of the nuclear bodies and the cytoplasm had the same excitation and emission maxima. Intranuclear bodies were also demonstrated in imprints stained with May-Grünwald-Giemsa.
Control of cardiac Ca2+ levels. Inhibitory actions of sphingosine on Ca2+ transients and L-type Ca2+ channel conductance.
Authors: P M McDonough, K Yasui, R Betto, G Salviati, C C Glembotski, P T Palade, R A Sabbadini
Journal: Circulation Research (1994)

The naturally occurring second messenger sphingosine (SPH) was examined for its ability to influence cardiac myocyte Ca2+ regulation. SPH inhibited intracellular Ca2+ transients in adult and neonatal rat ventricular myocytes. The inhibition was steeply dose dependent, with complete blockage of the Ca2+ transients occurring in the 20- to 25-mumol/L range. Whole-cell patch clamping revealed substantial inhibition of the L-type Ca2+ channel current (ICa) by SPH. The ability of SPH to block both the Ca2+ transients and ICa was not dependent on protein kinases, since the general protein kinase inhibitor H7 failed to prevent the actions of SPH. The specificity of the effect of SPH was determined in experiments showing that SPH analogues did not produce comparable effects. Neither the naturally occurring ceramide, N-stearoyl SPH, nor the cell-permeant ceramide, N-acetyl SPH, had SPH-like actions on the Ca2+ transients or L-type channel conductances. Caffeine-induced Ca2+ transients were also inhibited by the actions of SPH on cardiac sarcoplamic reticulum Ca2+ release, and the threshold for caffeine-induced Ca2+ release was raised. We conclude that SPH inhibits excitation-contraction coupling in cardiac myocytes by reducing the amount of entering "trigger Ca2+" for Ca(2+)-induced Ca2+ release and by simultaneously raising the threshold of the ryanodine receptor for Ca(2+)-induced Ca2+ release. Consequently, we propose that sphingolipids produced by the sphingomyelin signal transduction pathway could be physiologically relevant regulators of cardiac [Ca2+]i and therefore cardiac contractility.
A PHASE 2, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER TRIAL OF THE SAFETY AND EFFICACY OF PLASMID DNA EXPRESSING 2 ISOFORMS OF HEPATOCYTE GROWTH FACTOR IN PATIENTS WITH CRITICAL LIMB ISCHEMIA
Authors: Emerson C. Perin, Farrell Mendelsohn, Mark Davies, Hau Pham, Jorge Saucedo, Alan Hirsch, William Marston, Wook-Bum Pyun, Seung-Kee Min, Brian G. Peterson, Anthony Comerota, Donghoon Choi, Jeffrey Ballard, Douglas Losordo, Warren Sherman, William Hiatt, Melina Kibbe
Journal: Journal of the American College of Cardiology (2014)
Recurring episodes of meningitis (Mollaret's meningitis) with one showing an association with herpes simplex virus type 2
Authors: C. Bachmeyer, A. de la Blanchardière, J. Lepercq, R. Dh⩽ote, G. Grateau, M. Detilleux, M. Tournaire, B. Christoforov
Journal: Journal of Infection (1996)
Late Outcome After Arterial Switch Operation for Transposition of the Great Arteries
Authors: J Losay, A Touchot, A Serraf, A Litvinova, V Lambert, J D Piot, F Lacour-Gayet, A Capderou, C Planche
Journal: Circulation (2001)

Early and midterm results of the arterial switch operation (ASO) in transposition of the great arteries (TGA) are good, but late outcome data in large populations are still few.Twelve hundred patients had an ASO for TGA between 1982 and 1999, with prospective follow-up of 1095 survivors. Outcome measures included late death, reoperation, aortic insufficiency (AI), pulmonary stenosis (PS), and coronary anomaly. Median follow-up was 4.9 years (range 0.5 to 17 years). Late death occurred in 32 patients; survival was 88% at both 10 and 15 years. The hazard function for death declined rapidly, with no deaths after 5 years. Late mortality was correlated with reintervention and major events in the intensive care unit. Reoperation was performed in 103 patients, more often in complex TGA; the cause was mainly PS. Freedom from reintervention was 82% at 10 and 15 years, with a hazard function that declined rapidly but slowly increased after 3 years. At the last follow-up, PS was present in 3.9% of patients, and grade II or more AI was present in 3.2%, with a cumulative incidence of 9% at 15 years. Among the 278 patients who had a coronary arteriography, 8% had coronary lesions. Normal left ventricle and sinus rhythm were seen in 96.4% and 98.1%, respectively.Fifteen years after ASO, late mortality was low, with no deaths after 5 years; reoperation, mainly owing to PS, occurred throughout the follow-up. AI and coronary obstruction are rare but warrant further follow-up. Good left ventricular function and sinus rhythm are maintained.
DDX3, a DEAD Box RNA Helicase with Tumor Growth–Suppressive Property and Transcriptional Regulation Activity of the <i>p21waf1/cip1</i> Promoter, Is a Candidate Tumor Suppressor
Authors: Chi-Hong Chao, Chun-Ming Chen, Pei-Lin Cheng, Jing-Wen Shih, Ann-Ping Tsou, Yan-Hwa Wu Lee
Journal: Cancer Research (2006)

Abstract DDX3 is a DEAD box RNA helicase with diverse biological functions. Using colony formation assay, our results revealed that DDX3 inhibited the colony formation ability of various tumor cells, and this inhibition might be due to a reduced growth rate caused by DDX3. Additionally, we identified p21waf1/cip1, a cyclin-dependent kinase inhibitor, as a target gene of DDX3, and the up-regulation of p21waf1/cip1 expression accounted for the colony-suppressing activity of DDX3. Moreover, DDX3 exerted its transactivation function on p21waf1/cip1 promoter through an ATPase-dependent but helicase-independent mechanism, and the four Sp1 sites located within the −123 to −63 region, relative to the transcription start site of p21waf1/cip1 promoter, were essential for the response to DDX3. Furthermore, DDX3 interacted and cooperated with Sp1 to up-regulate the promoter activity of p21waf1/cip1. To determine the relevance of DDX3 in clinical cancers, the expression profile of DDX3 in various tumors was also examined. A declined expression of DDX3 mRNA and protein was found in ∼58% to 73% of hepatoma specimens, which led to the reduction of p21waf1/cip1 expression in a manner independent of p53 status. Additionally, an alteration of subcellular localization from nuclei to cytoplasm was also observed in &amp;gt;70% of cutaneous squamous cell carcinoma samples. Because DDX3 exhibits tumor suppressor functions, such as a growth-suppressive property and transcriptional activation of the p21waf1/cip1 promoter, and is inactivated through down-regulation of gene expression or alteration of subcellular localization in tumor cells, all these features together suggest that DDX3 might be a candidate tumor suppressor. (Cancer Res 2006; 66(13): 6579-88)
Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry
Authors: E Kunisch
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objectives:</b> To investigate the specificity of three anti-CD68 monoclonal antibodies (mAbs) for macrophages (Mφ) in immunohistochemistry (IHC) and flow cytometry (FACS). <b>Methods:</b> IHC was performed on cryostat sections of rheumatoid arthritis (RA) and osteoarthritis (OA) synovial membranes using the anti-CD68 mAbs KP1, EBM11, and PGM1, and the fibroblast (FB) markers CD90 and prolyl 4-hydroxylase. Expression of CD68 was also analysed by FACS on the monocytic cell lines THP-1 and U937, as well as on synovial fibroblasts (SFB), skin FB, and gingival FB (both surface and intracellular staining). <b>Results:</b> In IHC, there was an overlap between CD68 (mAbs KP1 and EBM11) and the FB markers CD90/prolyl 4-hydroxylase in the lining layer, diffuse infiltrates, and stroma of RA and OA synovial membranes. In FACS analysis of THP-1 and U937 cells, the percentage of cells positive for the anti-CD68 mAbs KP1 and EBM11 progressively increased from surface staining of unfixed cells, to surface staining of pre-fixed cells, to intracellular staining of the cells. Upon intracellular FACS of different FB, nearly all cells were positive for KP1 and EBM11, but only a small percentage for PGM1. In surface staining FACS, a small percentage of FB were positive for all three anti-CD68 mAbs. <b>Conclusion:</b> An overlap between CD68 (mAbs KP1 or EBM11) and the FB markers CD90 or prolyl 4-hydroxylase may prevent unequivocal identification of Mφ in synovial tissue by IHC or in monocytic cells and FB upon intracellular FACS. This may be due to sharing of common markers by completely different cell lineages.
Roles of antimicrobial peptides such as defensins in innate and adaptive immunity
Authors: J J Oppenheim
Journal: Annals of the Rheumatic Diseases (2003)

A number of antimicrobial peptides such as defensins have multiple functions in host defence. Defensins are produced not only by phagocytic cells and lymphocytes, but also by the epithelial cell lining of the gastrointestinal and genitourinary tracts, the tracheobronchial tree, and keratinocytes. Some are produced constitutively, whereas others are induced by proinflammatory cytokines and exogenous microbial products. Defensins produced by cells in the course of innate host defence serve as signals which initiate, mobilise, and amplify adaptive immune host defences. Administration of defensins with antigens to mice enhances both cellular (Th1-dependent) and humoral (Th2-dependent) cytokine production and immune responses. Linkage of defensins to weak tumour antigens potentiates their immunoadjuvant effects. Defensins use multiple cellular receptors, which endows them with the capacity to marshall adaptive host defences against microbial invaders.