tbuckley/cabot-search huggingface dataset:
Phase II Study of Radiotherapy Employing Proton Beam for Hepatocellular Carcinoma
Authors: Mitsuhiko Kawashima, Junji Furuse, Teiji Nishio, Masaru Konishi, Hiroshi Ishii, Taira Kinoshita, Michitaka Nagase, Keiji Nihei, Takashi Ogino
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the safety and efficacy of proton beam radiotherapy (PRT) for hepatocellular carcinoma. Patients and Methods Eligibility criteria for this study were: solitary hepatocellular carcinoma (HCC); no indication for surgery or local ablation therapy; no ascites; age ≥ 20 years; Zubrod performance status of 0 to 2; no serious comorbidities other than liver cirrhosis; written informed consent. PRT was administered in doses of 76 cobalt gray equivalent in 20 fractions for 5 weeks. No patients received transarterial chemoembolization or local ablation in combination with PRT. Results Thirty patients were enrolled between May 1999 and February 2003. There were 20 male and 10 female patients, with a median age of 70 years. Maximum tumor diameter ranged from 25 to 82 mm (median, 45 mm). All patients had liver cirrhosis, the degree of which was Child-Pugh class A in 20, and class B in 10 patients. Acute reactions of PRT were well tolerated, and PRT was completed as planned in all patients. Four patients died of hepatic insufficiency without tumor recurrence at 6 to 9 months. Three of these four patients had pretreatment indocyanine green retention rate at 15 minutes of more than 50%. After a median follow-up period of 31 months (16 to 54 months), only one patient experienced recurrence of the primary tumor, and 2-year actuarial local progression-free rate was 96% (95% CI, 88% to 100%). Actuarial overall survival rate at 2 years was 66% (48% to 84%). Conclusion PRT showed excellent control of the primary tumor, with minimal acute toxicity. Further study is warranted to scrutinize adequate patient selection in order to maximize survival benefit of this promising modality.
Induced Sputum Assessment in New York City Firefighters Exposed to World Trade Center Dust
Authors: Elizabeth M. Fireman, Yehuda Lerman, Eliezer Ganor, Joel Greif, Sharon Fireman-Shoresh, Paul J. Lioy, Gisela I. Banauch, Michael Weiden, Kerry J. Kelly, David J. Prezant
Journal: Environmental Health Perspectives (2004)

New York City Firefighters (FDNY-FFs) were exposed to particulate matter and combustion/pyrolysis products during and after the World Trade Center (WTC) collapse. Ten months after the collapse, induced sputum (IS) samples were obtained from 39 highly exposed FDNY-FFs (caught in the dust cloud during the collapse on 11 September 2001) and compared to controls to determine whether a unique pattern of inflammation and particulate matter deposition, compatible with WTC dust, was present. Control subjects were 12 Tel-Aviv, Israel, firefighters (TA-FFs) and 8 Israeli healthcare workers who were not exposed to WTC dust. All controls volunteered for this study, had never smoked, and did not have respiratory illness. IS was processed by conventional methods. Retrieved cells were differentially counted, and metalloproteinase-9 (MMP-9), particle size distribution (PSD), and mineral composition were measured. Differential cell counts of FDNY-FF IS differed from those of health care worker controls (p < 0.05) but not from those of TA-FFs. Percentages of neutrophils and eosinophils increased with greater intensity of WTC exposure (< 10 workdays or greater than or equal to 10 workdays; neutrophils p = 0.046; eosinophils p = 0.038). MMP-9 levels positively correlated to neutrophil counts (p = 0.002; r = 0.449). Particles were larger and more irregularly shaped in FDNY-FFs (1-50 microm; zinc, mercury, gold, tin, silver) than in TA-FFs (1-10 microm; silica, clays). PSD was similar to that of WTC dust samples. In conclusion, IS from highly exposed FDNY-FFs demonstrated inflammation, PSD, and particle composition that was different from nonexposed controls and consistent with WTC dust exposure.
Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31hiLy-6Cneg bone marrow precursors in a mouse model of asthma
Authors: Leonie S. van Rijt, Jan-Bas Prins, Pieter J. M. Leenen, Kris Thielemans, Victor C. de Vries, Henk C. Hoogsteden, Bart N. Lambrecht
Journal: Blood (2002)
Safety and Efficacy of Chymopapain (Chymodiactin) in Herniated Nucleus Pulposus With Sciatica
Authors: Manucher J. Javid
Journal: JAMA (1983)

A double-blind, randomized trial was conducted to compare the efficacy of intradiskal injection of chymopapain (Chymodiactin) with injection of placebo in patients with a herniated lumbar disk. Patients were randomly assigned to either placebo or drug regimens and followed up for six months. The primary measure of performance was agreement by patient and surgeon that further intervention was not necessary. At any time that patient and investigator agreed that treatment had failed, the patient was classified as a failure and the treatment code was broken. Of 53 placebo-treated patients, 31 failed by this criterion. Of 55 drug-treated patients, 15 failed. Placebo-treated patients who failed were allowed to receive drug treatment, and 29 (91%) of 32 were treated successfully. This study demonstrates that chymopapain is more effective than placebo for treatment of patients with a herniated lumbar disk.
Severe congenital mitral stenosis in infants.
Authors: P Moore, I Adatia, P J Spevak, J F Keane, S B Perry, A R Castaneda, J E Lock
Journal: Circulation (1994)

Despite current medical and surgical therapy, infants with symptomatic congenital mitral stenosis (CMS) continue to have high rates of morbidity and mortality. Catheter balloon dilation has been successful in relieving symptoms in a few older children with CMS but has not been evaluated in infants.We reviewed the records of 85 infants with CMS to assess severity of CMS, associated cardiac lesions, echocardiographic morphological appearance of the mitral valve, treatment, and outcome. There were five valve morphologies identified: "typical" hypoplastic mitral valve with symmetric papillary muscles (SYMM, 52%), supravalvar mitral ring (SVMR, 20%), double-orifice mitral valve (DOMV, 11%), hypoplastic mitral valve with asymmetric papillary muscles (ASYMM, 8%), and parachute mitral valve (PARA, 8%). Of the 85 infants, 31 (36%) were severely symptomatic, requiring intervention within the first 2 years. Balloon dilation was performed in 18 infants (age, 8.7 +/- 5.7 months; weight, 5.9 +/- 1.9 kg) and valve surgery in 13 (age, 10.9 +/- 5.9 months; weight, 6.7 +/- 2.1 kg). Balloon dilation decreased the peak transmitral gradient (LAa-LVED) > 30% in 15 of 18 initial attempts, from 20.3 +/- 8.2 to 10.9 +/- 4.9 mm Hg (P < .001), and the mitral valve area increased from 0.7 +/- 0.3 to 1.0 +/- 0.5 cm2/M2 (n = 10, P = .01). No infants died during the initial balloon dilation, although 2 of 3 died during a repeat procedure for restenosis. Other complications included significant mitral regurgitation in 7 of 18 patients (39%), 4 of whom had SVMR. Of the 18 infants, 8 (44%) had persistent symptomatic improvement at a mean follow-up of 14 months (range, 2 to 32 months). The 2-year survival after balloon dilation was 70%; 40% remained free of repeat intervention. Mitral valve surgery in 13 infants consisted of SVMR resections in 7, mitral valve replacements in 4, and LA-to-LV aortic valved homografts in 2. The operative mortality was 30%. Sustained improvement occurred in 8 (6 with SVMR) at 11 to 62 months of follow-up (mean, 30 months), with a 2-year survival of 60%.Infants with severe CMS have 2-year mortality rates approaching 40% regardless of treatment modality. Balloon dilation significantly reduces the transmitral gradient in the majority, but symptomatic improvement persists in only 40%. Procedure-related mortality was associated with repeat balloon dilation in patients with left ventricular hypoplasia. Balloon dilation of "typical" CMS can provide symptomatic relief in many infants, allowing postponement of valve replacement, although infants with SVMR do better with surgical management.
Temporal association between <i>Der pI</i> exposure, immediate hypersensitivity and clinical severity of eczema
Authors: A. J. W. Henderson, C. T. C. Kennedy, S. J. Thompson, F. Carswell
Journal: Allergy (1990)

Uncontrolled studies of avoidance of house dust mite ( Dermatophagoides pteronyssinus ) by atopic subjects have reported clinical improvement in the severity of eczema. The aim of the present study was to examine the temporal relationship between environmental exposure to the major mite allergen ( Der pI ) and clinical disease severity in children with chronic atopic eczema. Twelve children were identified as being house dust mite‐sensitive on the basis of skin prick test and RAST to Der pI. They were examined on two occasions with a median interval of 63 days. Clinical severity of eczema improved in nine children and deteriorated in two children during this period. Der pI concentration in dust from mattresses changed significantly in only three subjects and there was no correlation between changes in clinical severity and changes in environmental Der pI exposure. Change in RAST against Der pI did correlate positively with change in Der pI exposure (rho=0.56, P &lt;0.05) but these changes were not associated significantly with changes in eczema severity or skin test response to Der pI. It is concluded that the observed changes in clinical severity were unlikely to be due to immediate hypersensitivity responses to natural variations in Der pI concentrations in the personal environments of these subjects.
BCR-ABL Activity Is Critical for the Immunogenicity of Chronic Myelogenous Leukemia Cells
Authors: Katharina M. Brauer, Daniela Werth, Karin von Schwarzenberg, Anita Bringmann, Lothar Kanz, Frank Grünebach, Peter Brossart
Journal: Cancer Research (2007)

Abstract Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by excessive granulopoiesis due to the formation of the constitutively active tyrosine kinase BCR-ABL. An effective drug against CML is imatinib mesylate, a tyrosine kinase inhibitor acting on Abl kinases, c-KIT, and platelet-derived growth factor receptor. Recently, a study revealed that patients treated with imatinib showed impaired CTL responses compared with patients treated with IFN-α, which might be due to a treatment-induced reduction in immunogenicity of CML cells or immunosuppressive effects. In our study, we found that inhibition of BCR-ABL leads to a down-regulation of immunogenic antigens on the CML cells in response to imatinib treatment, which results in the inhibition of CML-directed immune responses. By treating CML cells with imatinib, we could show that the resulting inhibition of BCR-ABL leads to a decreased expression of tumor antigens, including survivin, adipophilin, hTERT, WT-1, Bcl-xL, and Bcl-2 in correlation to a decreased development of CML-specific CTLs. In contrast, this reduction in immunogenicity was not observed when a CML cell line resistant to the inhibitory effects of imatinib was used, but could be confirmed by transfection with specific small interfering RNA against BCR-ABL or imatinib treatment of primary CML cells. [Cancer Res 2007;67(11):5489–97]
Preferential Induction of EphB4 over EphB2 and Its Implication in Colorectal Cancer Progression
Authors: S. Ram Kumar, Jeffrey S. Scehnet, Eric J. Ley, Jasbir Singh, Valery Krasnoperov, Ren Liu, Parmeet K. Manchanda, Robert D. Ladner, Debra Hawes, Fred A. Weaver, Robert W. Beart, Gagandeep Singh, Cu Nguyen, Michael Kahn, Parkash S. Gill
Journal: Cancer Research (2009)

Abstract The receptor tyrosine kinase EphB2 is expressed by colon progenitor cells; however, only 39% of colorectal tumors express EphB2 and expression levels decline with disease progression. Conversely, EphB4 is absent in normal colon but is expressed in all 102 colorectal cancer specimens analyzed, and its expression level correlates with higher tumor stage and grade. Both EphB4 and EphB2 are regulated by the Wnt pathway, the activation of which is critically required for the progression of colorectal cancer. Differential usage of transcriptional coactivator cyclic AMP-responsive element binding protein–binding protein (CBP) over p300 by the Wnt/β-catenin pathway is known to suppress differentiation and increase proliferation. We show that the β-catenin-CBP complex induces EphB4 and represses EphB2, in contrast to the β-catenin-p300 complex. Gain of EphB4 provides survival advantage to tumor cells and resistance to innate tumor necrosis factor-related apoptosis-inducing ligand–mediated cell death. Knockdown of EphB4 inhibits tumor growth and metastases. Our work is the first to show that EphB4 is preferentially induced in colorectal cancer, in contrast to EphB2, whereby tumor cells acquire a survival advantage. [Cancer Res 2009;69(9):3736–45]
Integrated Array-Comparative Genomic Hybridization and Expression Array Profiles Identify Clinically Relevant Molecular Subtypes of Glioblastoma
Authors: Janice M. Nigro, Anjan Misra, Li Zhang, Ivan Smirnov, Howard Colman, Chandi Griffin, Natalie Ozburn, Mingang Chen, Edward Pan, Dimpy Koul, W.K. Alfred Yung, Burt G. Feuerstein, Kenneth D. Aldape
Journal: Cancer Research (2005)

Abstract Glioblastoma, the most aggressive primary brain tumor in humans, exhibits a large degree of molecular heterogeneity. Understanding the molecular pathology of a tumor and its linkage to behavior is an important foundation for developing and evaluating approaches to clinical management. Here we integrate array-comparative genomic hybridization and array-based gene expression profiles to identify relationships between DNA copy number aberrations, gene expression alterations, and survival in 34 patients with glioblastoma. Unsupervised clustering on either profile resulted in similar groups of patients, and groups defined by either method were associated with survival. The high concordance between these separate molecular classifications suggested a strong association between alterations on the DNA and RNA levels. We therefore investigated relationships between DNA copy number and gene expression changes. Loss of chromosome 10, a predominant genetic change, was associated not only with changes in the expression of genes located on chromosome 10 but also with genome-wide differences in gene expression. We found that CHI3L1/YKL-40 was significantly associated with both chromosome 10 copy number loss and poorer survival. Immortalized human astrocytes stably transfected with CHI3L1/YKL-40 exhibited changes in gene expression similar to patterns observed in human tumors and conferred radioresistance and increased invasion in vitro. Taken together, the results indicate that integrating DNA and mRNA-based tumor profiles offers the potential for a clinically relevant classification more robust than either method alone and provides a basis for identifying genes important in glioma pathogenesis.
Intravenous infusion of apolipoprotein E accelerates clearance of plasma lipoproteins in rabbits.
Authors: R W Mahley, K H Weisgraber, M M Hussain, B Greenman, M Fisher, T Vogel, M Gorecki
Journal: Journal of Clinical Investigation (1989)

Plasma cholesterol levels in cholesterol-fed rabbits were markedly reduced by the intravenous infusion or bolus injection of recombinant human apo E or rabbit plasma apo E. Administration of 6-70 mg of apo E resulted in an approximately 20-40% acute reduction in plasma cholesterol levels within 2-3 h. Plasma cholesterol levels remained reduced for 4-8 h after the administration of apo E. Furthermore, the intravenous injection of apo E reduced the plasma cholesterol levels in Watanabe heritable hyperlipidemic rabbits. The addition of apo E to [14C]cholesterol-labeled canine thoracic duct lymph or [14C]cholesterol-labeled chylomicrons resulted in accelerated plasma clearance of these diet-induced lipoproteins in normal rabbits, with the uptake occurring primarily in the liver. This study suggests that the amount or availability of apo E in the plasma of cholesterol-fed rabbits may be rate limiting for the normal clearance of diet-induced remnant lipoproteins.
Complementary Roles for Scavenger Receptor A and CD36 of Human Monocyte–derived Macrophages in Adhesion to Surfaces Coated with Oxidized Low-Density Lipoproteins and in Secretion of H2O2
Authors: Horst Maxeiner, Jens Husemann, Christian A. Thomas, John D. Loike, Joseph El Khoury, Samuel C. Silverstein
Journal: The Journal of Experimental Medicine (1998)

Oxidized low-density lipoprotein (oxLDL) is considered one of the principal effectors of atherogenesis. To explore mechanisms by which oxLDL affects human mononuclear phagocytes, we incubated these cells in medium containing oxLDL, acetylated LDL (acLDL), or native LDL, or on surfaces coated with these native and modified lipoproteins. The presence of soluble oxLDL, acLDL, or native LDL in the medium did not stimulate H2O2 secretion by macrophages. In contrast, macrophages adherent to surfaces coated with oxLDL secreted three- to fourfold more H2O2 than macrophages adherent to surfaces coated with acLDL or native LDL. Freshly isolated blood monocytes secreted little H2O2 regardless of the substrate on which they were plated. H2O2 secretion was maximal in cells maintained for 4–6 d in culture before plating on oxLDL-coated surfaces. Fucoidan, a known ligand of class A macrophage scavenger receptors (MSR-A), significantly reduced macrophage adhesion to surfaces coated with oxLDL or acLDL. Monoclonal antibody SMO, which blocks oxLDL binding to CD36, did not inhibit adhesion of macrophages to oxLDL-coated surfaces but markedly reduced H2O2 secretion by these cells. These studies show that MSR-A is primarily responsible for adhesion of macrophages to oxLDL-coated surfaces, that CD36 signals H2O2 secretion by macrophages adherent to these surfaces, and that substrate-bound, but not soluble, oxLDL stimulates H2O2 secretion by macrophages.
Remote Monitoring Reduces Healthcare Use and Improves Quality of Care in Heart Failure Patients With Implantable Defibrillators
Authors: Maurizio Landolina, Giovanni B. Perego, Maurizio Lunati, Antonio Curnis, Giuseppe Guenzati, Alessandro Vicentini, Gianfranco Parati, Gabriella Borghi, Paolo Zanaboni, Sergio Valsecchi, Maurizio Marzegalli
Journal: Circulation (2012)

Background— Heart failure patients with implantable cardioverter-defibrillators (ICDs) or an ICD for resynchronization therapy often visit the hospital for unscheduled examinations, placing a great burden on healthcare providers. We hypothesized that Internet-based remote interrogation systems could reduce emergency healthcare visits. Methods and Results— This multicenter randomized trial involving 200 patients compared remote monitoring with standard patient management consisting of scheduled visits and patient response to audible ICD alerts. The primary end point was the rate of emergency department or urgent in-office visits for heart failure, arrhythmias, or ICD-related events. Over 16 months, such visits were 35% less frequent in the remote arm (75 versus 117; incidence density, 0.59 versus 0.93 events per year; P =0.005). A 21% difference was observed in the rates of total healthcare visits for heart failure, arrhythmias, or ICD-related events (4.40 versus 5.74 events per year; P &lt;0.001). The time from an ICD alert condition to review of the data was reduced from 24.8 days in the standard arm to 1.4 days in the remote arm ( P &lt;0.001). The patients' clinical status, as measured by the Clinical Composite Score, was similar in the 2 groups, whereas a more favorable change in quality of life (Minnesota Living With Heart Failure Questionnaire) was observed from the baseline to the 16th month in the remote arm ( P =0.026). Conclusions— Remote monitoring reduces emergency department/urgent in-office visits and, in general, total healthcare use in patients with ICD or defibrillators for resynchronization therapy. Compared with standard follow-up through in-office visits and audible ICD alerts, remote monitoring results in increased efficiency for healthcare providers and improved quality of care for patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00873899.
T Cells Can Use Either T Cell Receptor or Cd28 Receptors to Absorb and Internalize Cell Surface Molecules Derived from Antigen-Presenting Cells
Authors: Inkyu Hwang, Jing-Feng Huang, Hidehiro Kishimoto, Anders Brunmark, Per A. Peterson, Michael R. Jackson, Charles D. Surh, Zeling Cai, Jonathan Sprent
Journal: The Journal of Experimental Medicine (2000)

At the site of contact between T cells and antigen-presenting cells (APCs), T cell receptor (TCR)–peptide–major histocompatibility complex (MHC) interaction is intensified by interactions between other molecules, notably by CD28 and lymphocyte function-associated antigen 1 (LFA-1) on T cells interacting with B7 (B7-1 and B7-2), and intracellular adhesion molecule 1 (ICAM-1), respectively, on APCs. Here, we show that during T cell–APC interaction, T cells rapidly absorb various molecules from APCs onto the cell membrane and then internalize these molecules. This process is dictated by at least two receptors on T cells, namely CD28 and TCR molecules. The biological significance of T cell uptake of molecules from APCs is unclear. One possibility is that this process may allow activated T cells to move freely from one APC to another and eventually gain entry into the circulation.
Impact of Gender on Access to the Renal Transplant Waiting List for Pediatric and Adult Patients
Authors: PUSHKAL P. GARG, SUSAN L. FURTH, BARBARA A. FIVUSH, NEIL R. POWE
Journal: Journal of the American Society of Nephrology (2000)

Abstract. While the public and policy-makers place a priority on equity in the organ allocation process, several studies suggest that women may be less likely than men to receive a renal transplant. However, the cause of this disparity and whether it exists among children with end-stage renal disease (ESRD) are unknown. To address these issues, two nationally representative cohorts of incident patients were examined: ( 1 ) 7594 adults with ESRD onset between 1986 and 1993 for whom detailed data were available from the medical record on health status; and ( 2 ) 3217 patients &lt;20 yr old who developed ESRD between 1988 and 1993. Patients were followed from initiation of dialysis for up to 10 yr until first activation on the United Network of Organ Sharing renal transplant waiting list. Access to the list for female and male patients with ESRD was compared using Cox proportional hazards models with adjustment for demographic, socioeconomic, and clinical factors. Crude rates of wait-listing per 100 person-years of ESRD were lower for female patients than male patients in both the pediatric (28.89 versus 34.18) and adult (3.94 versus 6.54) populations. Despite adjustment for numerous confounding factors, this gender-based disparity persisted in multivariate analysis. Among children with ESRD, female patients were 14% less likely to be listed than male patients (relative hazard [RH] 0.86; 95% confidence interval [CI], 0.78 to 0.93), and in the adult group, women were 18% less likely to be activated for transplant than men (RH 0.82; 95% CI, 0.72 to 0.93). These findings suggest that female patients of all ages with ESRD face barriers in being activated for cadaveric renal transplantation. Greater attention to this issue is necessary to improve equity in the organ allocation system and potentially improve the outcomes of female patients with ESRD.