tbuckley/cabot-search huggingface dataset:
A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome
Authors: S. Vadhan-Raj, L.E. Fayad, M.A. Fanale, B. Pro, A. Rodriguez, F.B. Hagemeister, C.E. Bueso-Ramos, X. Zhou, P.W. McLaughlin, N. Fowler, J. Shah, R.Z. Orlowski, F. Samaniego, M. Wang, J.E. Cortes, A. Younes, L.W. Kwak, N.J. Sarlis, J.E. Romaguera
Journal: Annals of Oncology (2011)

BackgroundTumor lysis syndrome (TLS) is a life-threatening disorder characterized by hyperuricemia and metabolic derangements. The efficacy of rasburicase, administered daily for 5 days, has been well established. However, the optimal duration of therapy is unknown in adults.Patients and methodsWe evaluated the efficacy of rasburicase (0.15 mg/kg) administered as single dose followed by as needed dosing (maximum five doses) versus daily dosing for 5 days in adult patients at risk for TLS.ResultsEighty of the 82 patients enrolled received rasburicase; 40 high risk [median uric acid (UA) 8.5 mg/dl; range, 1.5–19.7] and 40 potential risk (UA = 5.6 mg/dl; range, 2.4–7.4). Seventy-nine patients (99%) experienced normalization in their UA within 4 h after the first dose; 84% to an undetectable level (<0.7 mg/dl). Thirty-nine of 40 (98%) patients in the daily-dose arm and 34 of 40 (85%) patients in single-dose arm showed sustained UA response. Six high-risk patients within the single-dose arm required second dose for UA >7.5 mg/dl. Rasburicase was well tolerated; one patient with glucose-6-phosphate dehydrogenase deficiency developed methemoglobinemia and hemolysis.ConclusionsRasburicase is highly effective for prevention and management of hyperuricemia in adults at risk for TLS. Single-dose rasburicase was effective in most patients; only a subset of high-risk patients required a second dose.
Ex vivo expansion of human umbilical cord hematopoietic progenitor cells using a coculture system with human telomerase catalytic subunit (hTERT)–transfected human stromal cells
Authors: Yutaka Kawano, Masayoshi Kobune, Miki Yamaguchi, Kiminori Nakamura, Yoshinori Ito, Katsunori Sasaki, Sho Takahashi, Takafumi Nakamura, Hiroki Chiba, Tsutomu Sato, Takuya Matsunaga, Hiroshi Azuma, Kenji Ikebuchi, Hisami Ikeda, Junji Kato, Yoshiro Niitsu, Hirofumi Hamada
Journal: Blood (2002)
Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis
Authors: E. Schmidt, N.H. Thoennissen, A. Rudat, R. Bieker, C. Schliemann, R.M. Mesters, M. Zühlsdorf, C. Müller-Tidow, W.E. Berdel
Journal: Annals of Oncology (2008)
Characterization of pathogenic and prognostic factors of nonalcoholic steatohepatitis associated with obesity
Authors: Carmelo Garcia-Monzón, Elena Martín-Pérez, Oreste Lo Iacono, Miguel Fernández-Bermejo, Pedro L Majano, Arantxa Apolinario, Eduardo Larrañaga, Ricardo Moreno-Otero
Journal: Journal of Hepatology (2000)
Posttranscriptional deregulation of MYC via PTEN constitutes a major alternative pathway of MYC activation in T-cell acute lymphoblastic leukemia
Authors: Mélanie Bonnet, Marie Loosveld, Bertrand Montpellier, Jean-Marc Navarro, Benoit Quilichini, Christophe Picard, Julie Di Cristofaro, Claude Bagnis, Chantal Fossat, Lucie Hernandez, Emilie Mamessier, Sandrine Roulland, Ester Morgado, Christine Formisano-Tréziny, Willem A. Dik, Anton W. Langerak, Thomas Prebet, Norbert Vey, Gérard Michel, Jean Gabert, Jean Soulier, Elizabeth A. Macintyre, Vahid Asnafi, Dominique Payet-Bornet, Bertrand Nadel
Journal: Blood (2011)
Global pattern of experienced and anticipated discrimination reported by people with major depressive disorder: a cross-sectional survey
Authors: Antonio Lasalvia, Silvia Zoppei, Tine Van Bortel, Chiara Bonetto, Doriana Cristofalo, Kristian Wahlbeck, Simon Vasseur Bacle, Chantal Van Audenhove, Jaap van Weeghel, Blanca Reneses, Arunas Germanavicius, Marina Economou, Mariangela Lanfredi, Shuntaro Ando, Norman Sartorius, Juan J Lopez-Ibor, Graham Thornicroft
Journal: The Lancet (2012)
A Randomized Controlled Trial Comparing Foster Care and Institutional Care for Children With Signs of Reactive Attachment Disorder
Authors: Anna T. Smyke, Charles H. Zeanah, Mary Margaret Gleason, Stacy S. Drury, Nathan A. Fox, Charles A. Nelson, Donald Guthrie
Journal: American Journal of Psychiatry (2012)

Objective: The authors examined signs of emotionally withdrawn (inhibited type) and indiscriminately social (disinhibited type) reactive attachment disorder in Romanian children enrolled in a randomized trial of foster care compared with institutional care and in a comparison group of never-institutionalized children. Method: At baseline and when children were ages 30, 42, and 54 months and 8 years, caregivers were interviewed with the Disturbances of Attachment Interview to assess changes in signs of reactive attachment disorder in three groups of children: those receiving care as usual (including continued institutional care) (N=68); those placed in foster care after institutional care (N=68); and those who were never institutionalized (N=72). The impact of gender, ethnicity, and baseline cognitive ability was also examined. Results: On the Disturbances of Attachment Interview, signs of the inhibited type of reactive attachment disorder decreased after placement in foster care, and scores were indistinguishable from those of never-institutionalized children after 30 months. Signs of the disinhibited type were highest in the usual care group, lower in the foster care group, and lowest in the never-institutionalized group. Early placement in foster care (before age 24 months) was associated with fewer signs of the disinhibited type. Lower baseline cognitive ability was associated with more signs of the inhibited type in the usual care group and more signs of the disinhibited type in both groups. Conclusions: Signs of the inhibited type of reactive attachment disorder responded quickly to placement in foster care; signs of the disinhibited type showed less robust resolution with foster placement. Lower baseline cognitive ability was linked to signs of reactive attachment disorder.
Microscopic polyarteritis: a forgotten aetiology of haemoptysis and rapidly progressive glomerulonephritis.
Authors: S Zashin, R Fattor, D Fortin
Journal: Annals of the Rheumatic Diseases (1990)

A 76 year old white woman died from massive pulmonary haemorrhage nine days after she was admitted to Parkland Memorial Hospital for evaluation of haemoptysis and rapidly progressive glomerulonephritis. The differential diagnosis of haemoptysis with rapidly progressive glomerulonephritis is presented with particular emphasis on Wegener9s granulomatosis and microscopic polyarteritis. Necropsy showed a small vessel necrotising vasculitis associated with a focal segmental necrotising glomerulonephritis consistent with microscopic polyarteritis.
Three-dimensional morphology and gene expression in the Drosophila blastoderm at cellular resolution I: data acquisition pipeline.
Authors: Cris L Luengo Hendriks, Soile VE Keränen, Charless C Fowlkes, Lisa Simirenko, Gunther H Weber, Angela H DePace, Clara Henriquez, David W Kaszuba, Bernd Hamann, Michael B Eisen, Jitendra Malik, Damir Sudar, Mark D Biggin, David W Knowles
Journal: Genome biology (2006)

Abstract Background To model and thoroughly understand animal transcription networks, it is essential to derive accurate spatial and temporal descriptions of developing gene expression patterns with cellular resolution. Results Here we describe a suite of methods that provide the first quantitative three-dimensional description of gene expression and morphology at cellular resolution in whole embryos. A database containing information derived from 1,282 embryos is released that describes the mRNA expression of 22 genes at multiple time points in the Drosophila blastoderm. We demonstrate that our methods are sufficiently accurate to detect previously undescribed features of morphology and gene expression. The cellular blastoderm is shown to have an intricate morphology of nuclear density patterns and apical/basal displacements that correlate with later well-known morphological features. Pair rule gene expression stripes, generally considered to specify patterning only along the anterior/posterior body axis, are shown to have complex changes in stripe location, stripe curvature, and expression level along the dorsal/ventral axis. Pair rule genes are also found to not always maintain the same register to each other. Conclusion The application of these quantitative methods to other developmental systems will likely reveal many other previously unknown features and provide a more rigorous understanding of developmental regulatory networks.
Association of the Insulin Resistance Syndrome and Microalbuminuria among Nondiabetic Native Americans.The Inter-Tribal Heart Project
Authors: Christine M. Hoehner, Kurt J. Greenlund, Stephen Rith-Najarian, Michele L. Casper, William M. McClellan
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. This study investigated the association between microalbuminuria and the insulin resistance syndrome (IRS) among nondiabetic Native Americans. In a cross-sectional survey, age-stratified random samples were drawn from the Indian Health Service clinic lists for one Menominee and two Chippewa reservations. Information was collected from physical examinations, personal interviews, and blood and urine samples. The urinary albumin:creatinine ratio (ACR) was measured using a random spot urine sample. The IRS was defined by the number of composite traits: hypertension, impaired fasting glucose (IFG), high fasting insulin, low HDL cholesterol, and hypertriglyceridemia. Among the 934 eligible nondiabetic participants, 15.2% exhibited microalbuminuria. The prevalence of one, two, and three or more traits was 27.0, 16.6, and 7.4%, respectively. After controlling for age, sex, smoking, body mass index, education, and family histories of diabetes and kidney disease, the odds ratio (OR) for microalbuminuria was 1.8 (95% confidence interval [CI], 1.1 to 2.8) for one IRS trait, 1.8 (95% CI, 1.0 to 3.2) for two traits, and 2.3 (95% CI, 1.1 to 4.9) for three or more traits (<i>versus</i> no traits). The pattern of association appeared weaker among women compared with men. Of the individual IRS traits, only hypertension and IFG were associated with microalbuminuria. Among these nondiabetic Native Americans, the IRS was associated with a twofold increased prevalence of microalbuminuria. Health promotion efforts should focus on lowering the prevalence of hypertension, as well as glucose intolerance and obesity, in this population at high risk for renal and cardiovascular disease.
The Spectrum of Systemic Involvement in Adults Presenting with Renal Lesion and Mitochondrial tRNA(Leu) Gene Mutation
Authors: Bruno Guéry, Gabriel Choukroun, Laure-Hélène Noël, Pierre Clavel, Agnès Rötig, Sophie Lebon, Pierre Rustin, Christine Bellané-Chantelot, Béatrice Mougenot, Jean-Pierre Grünfeld, Dominique Chauveau
Journal: Journal of the American Society of Nephrology (2003)

The A3243G mutation of the mitochondrial tRNA(Leu) gene has been recently reported in rare patients with focal and segmental glomerulosclerosis (FSGS). However, the full spectrum of systemic and kidney manifestations in adults presenting with this mutation remains poorly defined. Assessment of renal and nonrenal manifestations was performed in nine patients with A3243G mutation and prominent kidney disease diagnosed in adulthood. At first renal evaluation, median age was 35 years. Renal lesions consisted of FSGS (n = 2), tubulointerstitial nephropathy (n = 3), or bilateral enlarged cystic kidneys (n = 1). All but one patient exhibited extrarenal manifestations: deafness (8 of 9) requiring hearing aid in half the cases, diabetes mellitus (3 of 9), neuromuscular involvement (2 of 9), hypertrophic cardiomyopathy (1 of 9), and macular dystrophy (1 of 9). After a median follow-up of 5 yr, five patients progressed to end-stage renal disease between the ages of 15 and 51 years, four being successfully transplanted. Similarly, extrarenal manifestations progressed since all patients had deafness and diabetes (including three posttransplants), while half had neuromuscular, cardiac, or retinal involvement. In the adult patients with A3243G mutation and renal involvement, preexisting deafness is almost consistently found. While FSGS remains the most typical lesion, tubulointerstitial nephropathy or bilateral, enlarged cystic kidneys may also be encountered. In most cases, diabetes mellitus, macular dystrophy, hypertrophic cardiomyopathy, or neuromuscular features occur later in the course of the disease. The severity of the clinical course is heterogeneous, with end-stage renal failure being reached between the second and sixth decades. Renal transplantation may be offered to these patients, despite a high incidence of steroid-induced diabetes mellitus.
Effect of the Second-Generation Vascular Disrupting Agent OXi4503 on Tumor Vascularity
Authors: Howard W. Salmon, Dietmar W. Siemann
Journal: Clinical Cancer Research (2006)

Abstract Purpose: As first-generation small-molecule vascular disrupting agents (VDA) have begun to enter clinical trials, second-generation agents are under active development. One such agent is the combretastatin A4 disodium phosphate (CA4P) analogue OXi4503 (CA1P). Experimental Design: C3H/HeJ mice bearing KHT sarcomas were treated with CA4P and OXi4503 and the effect on tumor vasculature was determined by evaluating the extent of vascular shutdown (Hoechst-33342 vessel staining) and tumor perfusion inhibition (dynamic contrast-enhanced magnetic resonance imaging). Dynamic contrast-enhanced magnetic resonance imaging and tumor necrosis end points also were used to examine the pathophysiologic tumor effects following repeated exposures to these agents. Results: Single doses of either agent (CA4P, 100 mg/kg; OXi4503, 25 mg/kg) resulted in an 80% to 90% reduction in tumor perfusion 4 hours after treatment. Whereas recovery in tumor perfusion was observed 48 hours posttreatment, this recovery was significantly slower in mice treated with OXi4503. Tumors re-treated with either VDA 72 hours after the first drug exposure showed a similar reduction and recovery in tumor perfusion. Histologic evidence showed the presence of a smaller viable rim after exposure to OXi4503 than that observed after CA4P treatment. Furthermore, the extent of recovery of tumor necrosis 72 hours after drug treatment was less for OXi4053. Conclusions: The present studies show that the second-generation VDA OXi4503 possesses significant antivascular effects in solid tumors. Importantly, the vasculature of tumors of mice that had received an initial dose this agent was as responsive to a subsequent treatment.
Cardiac function and modulation of sarcomeric function by length
Authors: L. M. Hanft, F. S. Korte, K. S. McDonald
Journal: Cardiovascular Research (2007)

The Frank–Starling relationship provides beat-to-beat regulation of ventricular function by matching ventricular input and output. This review addresses the subcellular mechanisms by which the ventricle adjusts its output (i.e. stroke volume) by changes in end-diastolic volume. The subcellular processes are placed in the context of the four phases of the cardiac cycle with emphasis on the sarcomeric properties that mediate the number of force-generating cross-bridges recruited during pressure development. Additional mechanistic insight is provided regarding the factors that regulate myocyte loaded shortening speeds, which are paramount for dictating ejection volume. Emphasis is placed on the interplay between cross-bridge-induced cooperative activation of the thin filament and cooperative deactivation of the thin filament induced by muscle shortening. The balance of these two properties seems to determine systolic haemodynamics, and how this balance is modulated by sarcomere length, in part, underlies the Frank–Starling relationship.
Intrarenal site of action of calcium on renin secretion in dogs.
Authors: B E Watkins, J O Davis, T E Lohmeier, R H Freeman
Journal: Circulation Research (1976)

We studied the effects of intrarenal calcium infusion on renin secretion in sodium-depleted dogs in an attempt to elucidate the major site of calcium-induced inhibition of renin release. Both calcium chloride and calcium gluconate reduced renal blood flow and renin secretion while renal perfusion pressure was unchanged. These data indicate that calcium inhibition of renin secretion did not occur primarily at the renal vascular receptor; decreased renal blood flow is usually associated with increased renin secretion. Calcium chloride infusion increased urinary chloride excretion without affecting sodium excretion, and calcium gluconate failed to increase either sodium or chloride excretion. Also, the filtered loads of sodium and chloride were unchanged during the calcium infusions. These results give no indication that calcium inhibited renin secretion by increasing the sodium or chloride load at the macula densa. The effects of intrarenal calcium infusion on renin release were also assessed in dogs with a nonfiltering kidney in which renal tubular mechanisms could not influence renin secretion. The observation that calcium still suppressed renin release in these dogs provides additional evidence that the the major effect of calcium involved nontubular mechanisms. Thus, it appears likely that calcium acted directly on the juxtaglomerular cells to inhibit renin secretion.
Nuclear YB-1 expression as a negative prognostic marker in nonsmall cell lung cancer
Authors: C. Gessner, C. Woischwill, A. Schumacher, U. Liebers, H. Kuhn, P. Stiehl, K. Jürchott, H.D. Royer, C. Witt, G. Wolff
Journal: European Respiratory Journal (2003)

The human Y-box binding protein, YB-1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB-1 has been associated with chemoresistance and poor prognosis of tumour patients. Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB-1 and p53, in order to evaluate the prognostic role of nuclear expression of YB-1. Cytoplasmic YB-1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB-1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB-1. Patients with nuclear YB-1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB-1 and wildtype p53 (median survival 15 months). This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y-box binding protien seems to be an independent prognostic marker.
Prediction of synergistic transcription factors by function conservation
Authors: Zihua Hu, Boyu Hu, James F Collins
Journal: Genome biology (2007)

Abstract Background Previous methods employed for the identification of synergistic transcription factors (TFs) are based on either TF enrichment from co-regulated genes or phylogenetic footprinting. Despite the success of these methods, both have limitations. Results We propose a new strategy to identify synergistic TFs by function conservation. Rather than aligning the regulatory sequences from orthologous genes and then identifying conserved TF binding sites (TFBSs) in the alignment, we developed computational approaches to implement the novel strategy. These methods include combinatorial TFBS enrichment utilizing distance constraints followed by enrichment of overlapping orthologous genes from human and mouse, whose regulatory sequences contain the enriched TFBS combinations. Subsequently, integration of function conservation from both TFBS and overlapping orthologous genes was achieved by correlation analyses. These techniques have been used for genome-wide promoter analyses, which have led to the identification of 51 homotypic TF combinations; the validity of these approaches has been exemplified by both known TF-TF interactions and function coherence analyses. We further provide computational evidence that our novel methods were able to identify synergistic TFs to a much greater extent than phylogenetic footprinting. Conclusion Function conservation based on the concordance of combinatorial TFBS enrichment along with enrichment of overlapping orthologous genes has been proven to be a successful means for the identification of synergistic TFs. This approach avoids the limitations of phylogenetic footprinting as it does not depend upon sequence alignment. It utilizes existing gene annotation data, such as those available in GO, thus providing an alternative method for functional TF discovery and annotation.
CD8 T Cell Recognition of Endogenously Expressed Epstein-Barr Virus Nuclear Antigen 1
Authors: Steven P. Lee, Jill M. Brooks, Hatim Al-Jarrah, Wendy A. Thomas, Tracey A. Haigh, Graham S. Taylor, Sibille Humme, Aloys Schepers, Wolfgang Hammerschmidt, John L. Yates, Alan B. Rickinson, Neil W. Blake
Journal: The Journal of Experimental Medicine (2004)

The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I–restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon γ release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter–dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies.
The BCR-ABL Story: Bench to Bedside and Back
Authors: Stephane Wong, Owen N. Witte
Journal: Annual Review of Immunology (2004)

The twenty-first century is beginning with a sharp turn in the field of cancer therapy. Molecular targeted therapies against specific oncogenic events are now possible. The BCR-ABL story represents a notable example of how research from the fields of cytogenetics, retroviral oncology, protein phosphorylation, and small molecule chemical inhibitors can lead to the development of a successful molecular targeted therapy. Imatinib mesylate (Gleevec, STI571, or CP57148B) is a direct inhibitor of ABL (ABL1), ARG (ABL2), KIT, and PDGFR tyrosine kinases. This drug has had a major impact on the treatment of chronic myelogenous leukemia (CML) as well as other blood neoplasias and solid tumors with etiologies based on activation of these tyrosine kinases. Analysis of CML patients resistant to BCR-ABL suppression by Imatinib mesylate coupled with the crystallographic structure of ABL complexed to this inhibitor have shown how structural mutations in ABL can circumvent an otherwise potent anticancer drug. The successes and limitations of Imatinib mesylate hold general lessons for the development of alternative molecular targeted therapies in oncology.