tbuckley/cabot-search huggingface dataset:
Treatment for Acute Myelogenous Leukemia by Low-Dose, Total-Body, Irradiation-Based Conditioning and Hematopoietic Cell Transplantation From Related and Unrelated Donors
Authors: Ute Hegenbart, Dietger Niederwieser, Brenda M. Sandmaier, Michael B. Maris, Judith A. Shizuru, Hildegard Greinix, Catherine Cordonnier, Bernard Rio, Alois Gratwohl, Thoralf Lange, Haifa Al-Ali, Barry Storer, David Maloney, Peter McSweeney, Thomas Chauncey, Ed Agura, Benedetto Bruno, Richard T. Maziarz, Finn Petersen, Rainer Storb
Journal: Journal of Clinical Oncology (2005)

The use of low-dose, irradiation-based preparative regimens have allowed the extension of allografting to older and medically infirm patients. The study reported here assessed outcomes for patients with acute myeloid leukemia (AML) in different stages of their disease, who were not considered candidates for conventional hematopoietic cell transplantation (HCT) because of age and/or other known risk factors and were given minimal conditioning followed by HCT from related or unrelated donors.The present study included 122 patients with AML, who were conditioned with 2 Gy total-body irradiation (TBI) on day 0 with or without preceding fludarabine (30 mg/m2/d from days -4 to -2), and given postgrafting cyclosporine at 6.25 mg/kg twice daily from day -3 and mycophenolate mofetil at 15 mg/kg twice daily from day 0.Durable engraftment was observed in 95% of the patients. Cumulative incidences of acute graft-versus-host disease grades 2 to 4 at 6 months were 35% after related and 42% after unrelated HCT, respectively. With a median follow-up of 44 months (range, 26 to 79 months), 51 patients were alive, of whom 48 were in complete remission (CR). Cumulative nonrelapse mortalities were 10% and 22%, and cumulative mortalities from disease progression were 47% and 33% at 2 years for related and unrelated recipients, respectively. Overall, 2-year survival was 48%, and disease-free survival was 44%. Patients receiving transplantation in CR1 had 2-year overall survivals of 44% after related and 63% after unrelated HCT, respectively.We conclude that HCT from related and unrelated donors after low-dose TBI is a promising treatment for elderly patients with AML.
Ki-67 Is an Independent Predictor of Bladder Cancer Outcome in Patients Treated with Radical Cystectomy for Organ-Confined Disease
Authors: Vitaly Margulis, Shahrokh F. Shariat, Raheela Ashfaq, Arthur I. Sagalowsky, Yair Lotan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To determine the association of the cell proliferative marker Ki-67 with pathologic features and disease prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder. Methods: Immunohistochemical staining for Ki-67 was done on serial cuts from tissue microarrays containing cystectomy specimens from 9 patients without bladder cancer and 226 consecutive patients with bladder TCC. We also assessed malignant lymph nodes from 50 of the 226 cystectomy patients. Results: Ki-67 expression was increased in 42.5% cystectomy specimens and in 54% metastatic lymph nodes. In contrast, it was absent in all nine benign cystectomy specimens. Ki-67 overexpression was associated with advanced pathologic stage, higher grade, lymphovascular invasion, and metastases to lymph nodes (P = 0.001, 0.040, 0.031, and 0.036, respectively). In multivariate analyses, pathologic stage and lymph node metastases were independent predictors of disease recurrence and bladder cancer-specific mortality. In the subgroup of patients with organ-confined disease (&amp;lt;pT3 N0; n = 91), excluding patients who received neoadjuvant or adjuvant chemotherapy, Ki-67 status was an independent predictor of both disease recurrence (risk ratio, 7.591; P = 0.001) and bladder cancer-specific mortality (risk ratio, 4.045; P = 0.041). Conclusions: Ki-67 overexpression is associated with features of aggressive bladder TCC and adds independent prognostic information to standard pathologic features for prediction of clinical outcome after radical cystectomy.
A T Cell Receptor CDR3β Loop Undergoes Conformational Changes of Unprecedented Magnitude Upon Binding to a Peptide/MHC Class I Complex
Authors: Jean-Baptiste Reiser, Claude Grégoire, Claudine Darnault, Thomas Mosser, Annick Guimezanes, Anne-Marie Schmitt-Verhulst, Juan Carlos Fontecilla-Camps, Gilbert Mazza, Bernard Malissen, Dominique Housset
Journal: Immunity (2002)
Infective Complications After Prostate Biopsy: Outcome of the Global Prevalence Study of Infections in Urology (GPIU) 2010 and 2011, A Prospective Multinational Multicentre Prostate Biopsy Study
Authors: Florian M.E. Wagenlehner, Edgar van Oostrum, Peter Tenke, Zafer Tandogdu, Mete Çek, Magnus Grabe, Björn Wullt, Robert Pickard, Kurt G. Naber, Adrian Pilatz, Wolfgang Weidner, Truls E. Bjerklund-Johansen
Journal: European Urology (2012)
Red Blood Cell Contamination of the Final Cell Product Impairs the Efficacy of Autologous Bone Marrow Mononuclear Cell Therapy
Authors: Birgit Assmus, Torsten Tonn, Florian H. Seeger, Chang-Hwan Yoon, David Leistner, Jens Klotsche, Volker Schächinger, Erhard Seifried, Andreas M. Zeiher, Stefanie Dimmeler
Journal: Journal of the American College of Cardiology (2010)
Racial and Ethnic Disparities in Risk and Survival in Children With Neuroblastoma: A Children's Oncology Group Study
Authors: Tara O. Henderson, Smita Bhatia, Navin Pinto, Wendy B. London, Patrick McGrady, Catherine Crotty, Can-Lan Sun, Susan L. Cohn
Journal: Journal of Clinical Oncology (2010)

Purpose Although health disparities are well-described for many cancers, little is known about racial and ethnic disparities in neuroblastoma. To evaluate differences in disease presentation and survival by race and ethnicity, data from the Children's Oncology Group (COG) were analyzed. Patients and Methods The racial/ethnic differences in clinical and biologic risk factors, and outcome of patients with neuroblastoma enrolled on COG ANBL00B1 between 2001 and 2009 were investigated. Results A total of 3,539 patients (white, 72%; black, 12%; Hispanic, 12%; Asian, 4%; and Native American, &lt; 1%) with neuroblastoma were included. The 5-year event-free survival (EFS) rates were 67% for whites (95% CI, 65% to 69%), 69% for Hispanics (95% CI, 63% to 74%), 62% for Asians (95% CI, 51% to 71%), 56% for blacks (95% CI, 50% to 62%), and 37% for Native American (95% CI, 17% to 58%). Blacks (P &lt; .001) and Native Americans (P = .04) had a higher prevalence of high-risk disease than whites, and significantly worse EFS (P = .01 and P = .002, respectively). Adjustment for risk group abrogated these differences. However, closer examination of the EFS among high-risk patients who remained event free for 2 years or longer, revealed a higher prevalence of late-occurring events among blacks compared with whites (hazard ratio, 1.5; 95% CI, 1.0 to 2.3; P = .04). Conclusion Black and Native American patients with neuroblastoma have a higher prevalence of high-risk disease, accounting for their worse EFS when compared with whites. The higher prevalence of late-occurring events among blacks with high-risk disease suggests that this population may be more resistant to chemotherapy. Studies focused on delineating the genetic basis for the racial disparities observed in this study are planned.
Altered IFNγ Signaling and Preserved Susceptibility to Activated Natural Killer Cell–Mediated Lysis of BCR/ABL Targets
Authors: Christelle Cebo, Ioannis A. Voutsadakis, Sylvie Da Rocha, Jean-Henri Bourhis, Abdelali Jalil, Bruno Azzarone, Ali G. Turhan, Mounira Chelbi-Alix, Salem Chouaib, Anne Caignard
Journal: Cancer Research (2005)

Abstract Previous studies have shown that BCR/ABL oncogene, the molecular counterpart of the Ph1 chromosome, could represent a privileged target to natural killer (NK) cells. In the present study, we showed that activated peripheral NK cells killed high-level BCR/ABL transfectant UT-7/9 derived from the pluripotent hematopoietic cell line UT-7 with a high efficiency. To further define the mechanisms controlling BCR/ABL target susceptibility to NK-mediated lysis, we studied the effect of IFNγ, a key cytokine secreted by activated NK cells, on the lysis of these targets. Treatment of UT-7, UT-7/neo, and low BCR/ABL transfectant UT-7/E8 cells with IFNγ resulted in a dramatic induction of human leukocyte antigen class I (HLA-I) molecules and subsequently in their reduced susceptibility to NK-mediated cytolysis likely as a consequence of inhibitory NK receptors engagement. In contrast, such treatment neither affected HLA-I expression on transfectants expressing high level of BCR/ABL (UT-7/9) nor modulated their lysis by NK cells. Our data further show that the high-level BCR/ABL in UT-7/9 cells display an altered IFNγ signaling, as evidenced by a decrease in IFN regulatory factor-1 (IRF-1) and signal transducers and activators of transcription (STAT) 1 induction and activation in response to IFNγ, whereas this pathway is normal in UT-7 and UT-7/E8 cells. A decreased HLA-I induction and nuclear phospho-STAT1 nuclear translocation were also observed in blasts from most chronic myelogenous leukemia patients in response to IFNγ. These results outline the crucial role of IFNγ in the control of target cell susceptibility to lysis by activated NK cells and indicate that the altered response to IFNγ in BCR/ABL targets may preserve these cells from the cytokine-induced negative regulatory effect on their susceptibility to NK-mediated lysis.
Could a proportion of familial breast cancer patients testing negative to BRCA1 and BRCA2 in fact be false negatives in the Republic of Ireland?
Authors: Fatima Aloraifi, Trudi McDevitt, Nuala Cody, Marie Meanie, Cliona de Baroid, Rosemarie Kelly, Adrian Bracken, Andrew Green, James Geraghty
Journal: International Journal of Surgery (2012)
What a Cardiologist Needs to Know About Patients With Human Immunodeficiency Virus Infection
Authors: Priscilla Y. Hsue, David D. Waters
Journal: Circulation (2005)

A 48-year-old man with human immunodeficiency virus (HIV) infection developed chronic chest pain that started after a bout of pneumonia. He has hypertension and has smoked cigarettes in the past. His current medications include Kaletra and Combivir. His total cholesterol was 331 mg/L, his HDL cholesterol was 27 mg/L, his triglycerides were 935 mg/L, and his LDL cholesterol could not be calculated. How should this patient be evaluated and managed?
Expression and Activity of Src Regulate Interleukin-8 Expression in Pancreatic Adenocarcinoma Cells: Implications for Angiogenesis
Authors: Jose G. Trevino, Justin M. Summy, Michael J. Gray, Monique B. Nilsson, Donald P. Lesslie, Cheryl H. Baker, Gary E. Gallick
Journal: Cancer Research (2005)

Abstract Interleukin-8 (IL-8) is an angiogenic factor that promotes growth of pancreatic tumors. The purpose of this study was to determine if c-Src, a protein tyrosine kinase frequently overexpressed in pancreatic cancer, regulated IL-8 expression and to elucidate the Src-mediated signaling pathways that contribute to angiogenesis in pancreatic adenocarcinoma cells. In a panel of pancreatic cancer cell lines, expression of total and activated Src correlated with IL-8 production. Furthermore, ectopic expression of activated Src in PANC-1 cells with low endogenous Src activity significantly increased IL-8 production (P &amp;lt; 0.005). In contrast, pharmacologic inhibition of endogenous c-Src kinase activity or small interfering RNA–mediated “knockdown” of c-Src expression in L3.6pl cells with high Src expression and activity caused significant decreases in IL-8 production (P &amp;lt; 0.005). Inhibition of c-Src activity resulted in decreased phosphorylation of Akt, p38, and extracellular signal-regulated kinase (Erk)-1/2. Significant (P &amp;lt; 0.005) dose-dependent decreases were observed in IL-8 expression by inhibiting Src-dependent signaling molecules Erk-1/2 and p38 but not phosphatidylinositol 3-kinase. To assess the relevance of Src inhibition to angiogenesis, in vivo gelfoam assays were done. Robust infiltration of vessels was observed in gelfoam saturated with conditioned medium from pancreatic carcinoma cells. This angiogenesis was nearly abrogated in gelfoams saturated with conditioned medium from cells treated with the Src family kinase inhibitor, PP2 (P &amp;lt; 0.001). Thus, c-Src regulates critical “downstream” signaling pathways that contribute to expression of IL-8 in human pancreatic tumor cells, suggesting c-Src may be a target for therapeutic intervention in pancreatic adenocarcinoma.
<i>N-</i>Methyl-<scp>d</scp>-Aspartate Receptor Type 2B Is Epigenetically Inactivated and Exhibits Tumor-Suppressive Activity in Human Esophageal Cancer
Authors: Myoung Sook Kim, Keishi Yamashita, Jin Hyen Baek, Hannah Lui Park, Andre Lopes Carvalho, Motonobu Osada, Mohammad Obaidul Hoque, Sunil Upadhyay, Masaki Mori, Chulso Moon, David Sidransky
Journal: Cancer Research (2006)

Abstract Promoter hypermethylation accompanied by gene silencing is a common feature of human cancers. We identified previously several new tumor suppressor genes based on pharmacologic unmasking of the promoter region and detection of reexpression on microarray analysis. In this study, we modified the selection of candidates from our previous microarray data by excluding genes that showed basal expression in cancer cell lines. With the new method, we found novel methylated genes with 90% accuracy. Among these 33 novel methylated genes that we identified in esophageal squamous cell carcinoma (ESCC) cell lines, N-methyl-d-aspartate receptor type 2B (NMDAR2B) was of particular interest. NMDAR2B was methylated in 95% of primary human ESCC tissue specimens and 12 ESCC cell lines by sequence analysis. NMDAR2B expression was silenced in all 12 ESCC cell lines and was reactivated by the demethylating agent 5-aza-2′-deoxycytidine. Moreover, reintroduction of the gene was accompanied by marked Ca2+-independent apoptosis in ESCC cell lines, suggesting that NMDAR2B can suppress tumor growth. Thus, NMDAR2B promoter methylation is common in ESCC, abrogating gene transcription and leading to cellular resistance to apoptosis. (Cancer Res 2006; 66(7): 3409-18)
Evidence for distinct calcium channel agonist and antagonist binding sites in intact cultured embryonic chick ventricular cells.
Authors: R T Lee, T W Smith, J D Marsh
Journal: Circulation Research (1987)

To determine whether calcium channel agonists and antagonists bind to distinct pharmacologically active sites, the binding of dihydropyridine calcium channel agonists and antagonists was related to calcium flux and contractile state in primary monolayer cultures of spontaneously contracting chick embryo ventricular cells. Equilibrium binding studies using the antagonist (+)-[3H]PN200-110 demonstrated equilibrium binding to intact, beating cells consistent with a single class of binding sites (KD, 1.1 nM; Bmax, 40 fmol/mg protein). Membrane depolarization of the intact cells by incubation in 30 mM potassium caused a 91% increase in the apparent number of (+)-PN200-110 binding sites (Bmax 76 fmol/mg protein), but no significant change in the KD (1.2 nM). The (+)-PN200-110 produced a concentration-dependent decrease in calcium uptake (IC50 2.2 nM) and contractile amplitude (IC50 5.6 nM). The calcium channel agonist, (+/-)-[3H]BAY k 8644, bound to two distinct binding sites with high affinity (KD 1.0 nM) and low affinity (KD 1.9 microM). The (+/-)-BAY k 8644 produced biphasic modulation of calcium flux and contractile state. At concentrations of 100 nM or less, (+/-)-BAY k 8644 increased calcium flux and contractile amplitude, consistent with drug interaction with the high affinity agonist site. However, at higher concentrations, the stimulatory effect of (+/-)-BAY k 8644 on calcium flux and contractile amplitude was abolished, a finding that is consistent with drug interaction with the low affinity antagonist site.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Interactive Diary: A New Telemedicine System Enabling Flexible Diet and Insulin Therapy While Improving Quality of Life
Authors: Maria C.E. Rossi, Antonio Nicolucci, Paolo Di Bartolo, Daniela Bruttomesso, Angela Girelli, Francisco J. Ampudia, David Kerr, Antonio Ceriello, Carmen De La Questa Mayor, Fabio Pellegrini, David Horwitz, Giacomo Vespasiani
Journal: Diabetes Care (2009)

OBJECTIVE Widespread use of carbohydrate counting is limited by its complex education. In this study we compared a Diabetes Interactive Diary (DID) with standard carbohydrate counting in terms of metabolic and weight control, time required for education, quality of life, and treatment satisfaction. RESEARCH DESIGN AND METHODS Adults with type 1 diabetes were randomly assigned to DID (group A, n = 67) or standard education (group B, n = 63) and followed for 6 months. A subgroup also completed the SF-36 Health Survey (SF-36) and World Health Organization-Diabetes Treatment Satisfaction Questionnaire (WHO-DTSQ) at each visit. RESULTS Of 130 patients (aged 35.7 ± 9.4 years; diabetes duration 16.5 ± 10.5 years), 11 dropped out. Time for education was 6 h (range 2–15 h) in group A and 12 h (2.5–25 h) in group B (P = 0.07). A1C reduction was similar in both groups (group A from 8.2 ± 0.8 to 7.8 ± 0.8% and group B from 8.4 ± 0.7 to 7.9 ± 1.1%; P = 0.68). Nonsignificant differences in favor of group A were documented for fasting blood glucose and body weight. No severe hypoglycemic episode occurred. WHO-DTSQ scores increased significantly more in group A (from 26.7 ± 4.4 to 30.3 ± 4.5) than in group B (from 27.5 ± 4.8 to 28.6 ± 5.1) (P = 0.04). Role Physical, General Health, Vitality, and Role Emotional SF-36 scores improved significantly more in group A than in group B. CONCLUSIONS DID is at least as effective as traditional carbohydrate counting education, allowing dietary freedom for a larger proportion of type 1 diabetic patients. DID is safe, requires less time for education, and is associated with lower weight gain. DID significantly improved treatment satisfaction and several quality-of-life dimensions.
Ventilatory variables in normal children during rest and exercise
Authors: M. Rosenthal, A. Bush
Journal: European Respiratory Journal (2000)

The aim of this study was to provide a complete description of normal ventilation at rest and exercise in children and to determine how best to correct for body size. One-hundred and six children aged 8-17 years (55 male) underwent incremental bicycle exercise testing from rest to exhaustion in 3 min, 15 W.m(-2) steps and thence through 9 min recovery. All variables were calculated using helium dilution mixed expired gas analysis together with measures of alveolar gas concentrations from continuous measurement at the mouth, all via an AMIS 2000 quadrupole mass spectrometer. Surface area was the best single measure to correct for body size but always explained &lt;37% of the variance. Thus for example, surface area corrected oxygen consumption at rest in males was greater than females. Data is presented at rest, each work load and at "maximum" exercise. When presented per watt of work at each work load, this permits comparison of adaptability to exercise between sexes and age groups. Exercise appears to terminate when respiration reaches 45 and 40 breaths-min(-1) in males and females respectively and when alveolar oxygen concentrations rise. This simple protocol and near complete data set ought to permit accurate comparison with disease groups.
Health is global: proposals for a UK Government-wide strategy
Authors: Liam Donaldson, Nicholas Banatvala
Journal: The Lancet (2007)

Global health enables the harmonisation of international and domestic-health concerns-its outlook is much wider than a development or foreign-assistance perspective alone. Engaging globally in health requires the creation of relevant and effective partnerships to implement solutions for shared or common problems. To build on the UK's achievements and leadership in global health, the central government Department of Health is now leading the development of a UK Government-wide global strategy. This paper describes the rationale and process for developing the new UK Government-wide strategy for global health and highlights some of the issues that must be discussed.
Inhibition of apolipoprotein B100 secretion by lipid-induced hepatic endoplasmic reticulum stress in rodents
Authors: Tsuguhito Ota, Constance Gayet, Henry N. Ginsberg
Journal: Journal of Clinical Investigation (2008)

ER stress can cause hepatic insulin resistance and steatosis. Increased VLDL secretion could protect the liver from ER stress–induced steatosis, but the effect of lipid-induced ER stress on the secretion of VLDL is unknown. To determine the effect of lipids on hepatic ER stress and VLDL secretion, we treated McA-RH7777 liver cells with free fatty acids. Prolonged exposure increased cell triglycerides, induced steatosis, and increased ER stress. Effects on apoB100 secretion, which is required for VLDL assembly, were parabolic, with moderate free fatty acid exposure increasing apoB100 secretion, while greater lipid loading inhibited apoB100 secretion. This decreased secretion at higher lipid levels was due to increased protein degradation through both proteasomal and nonproteasomal pathways and was dependent on the induction of ER stress. These findings were supported in vivo, where intravenous infusion of oleic acid (OA) in mice increased ER stress in a duration-dependent manner. apoB secretion was again parabolic, stimulated by moderate, but not prolonged, OA infusion. Inhibition of ER stress was able to restore OA-stimulated apoB secretion after prolonged OA infusion. These results suggest that excessive ER stress in response to increased hepatic lipids may decrease the ability of the liver to secrete triglycerides by limiting apoB secretion, potentially worsening steatosis.
AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs
Authors: Federica Collino, Stefania Bruno, Danny Incarnato, Daniela Dettori, Francesco Neri, Paolo Provero, Margherita Pomatto, Salvatore Oliviero, Ciro Tetta, Peter J. Quesenberry, Giovanni Camussi
Journal: Journal of the American Society of Nephrology (2015)

Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell-promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal cells depleted of Drosha to alter microRNA expression. Drosha-knockdown cells produced extracellular vesicles that did not differ from those of wild-type cells in quantity, surface molecule expression, and internalization within renal tubular epithelial cells. However, these vesicles showed global downregulation of microRNAs. Whereas wild-type mesenchymal stromal cells and derived vesicles administered intravenously induced morphologic and functional recovery in AKI, the Drosha-knockdown counterparts were ineffective. RNA sequencing analysis showed that kidney genes deregulated after injury were restored by treatment with mesenchymal stromal cells and derived vesicles but not with Drosha-knockdown cells and vesicles. Gene ontology analysis showed in AKI an association of downregulated genes with fatty acid metabolism and upregulated genes with inflammation, matrix-receptor interaction, and cell adhesion molecules. These alterations reverted after treatment with wild-type mesenchymal stromal cells and extracellular vesicles but not after treatment with the Drosha-knockdown counterparts. In conclusion, microRNA depletion in mesenchymal stromal cells and extracellular vesicles significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of microRNAs in recovery after AKI.