tbuckley/cabot-search huggingface dataset:
Low-Intensity Therapy in Adults with Burkitt's Lymphoma
Authors: Kieron Dunleavy, Stefania Pittaluga, Margaret Shovlin, Seth M. Steinberg, Diane Cole, Cliona Grant, Brigitte Widemann, Louis M. Staudt, Elaine S. Jaffe, Richard F. Little, Wyndham H. Wilson
Journal: New England Journal of Medicine (2013)

Burkitt's lymphoma is an aggressive B-cell lymphoma that occurs in children and adults and is largely curable with the use of intensive and toxic chemotherapy. Current treatments are less effective and have more severe side effects in adults and patients with immunodeficiency than in children.We studied low-intensity treatment consisting of infused etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (EPOCH-R) in patients with untreated Burkitt's lymphoma. Two EPOCH-R regimens were tested: a standard dose-adjusted combination in human immunodeficiency virus (HIV)-negative patients (DA-EPOCH-R group) and a lower-dose short-course combination with a double dose of rituximab in HIV-positive patients (SC-EPOCH-RR group).A total of 30 consecutive patients were treated; 19 patients were in the DA-EPOCH-R group, and 11 in the SC-EPOCH-RR group. The overall median age of the patients was 33 years, and 40% were 40 years of age or older; 73% of the patients had intermediate-risk disease, and 10% had high-risk disease. The principal toxic events, fever and neutropenia, were observed during 22% of the DA-EPOCH-R treatment cycles and 10% of the SC-EPOCH-RR treatment cycles. The tumor lysis syndrome developed in 1 patient; no treatment-related deaths occurred. The median cumulative doses of doxorubicin-etoposide and cyclophosphamide administered in the SC-EPOCH-RR group were 47% and 57% lower, respectively, than those administered in the DA-EPOCH-R group. With median follow-up times of 86 months in the DA-EPOCH-R group and 73 months in the SC-EPOCH-RR group, the rates of freedom from progression of disease and overall survival were, respectively, 95% and 100% with DA-EPOCH-R and 100% and 90% with SC-EPOCH-RR. None of the patients died from Burkitt's lymphoma.In this uncontrolled prospective study, low-intensity EPOCH-R-based treatment was highly effective in adults with sporadic or immunodeficiency-associated Burkitt's lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov numbers, NCT00001337 and NCT00006436.).
THE IMPACT OF CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH RANGE OF LEFT VENTRICULAR EJECTION FRACTIONS IN MADIT-CRT
Authors: Valentina Kutyifa, Wojciech Zareba, Scott McNitt, Scott Solomon, Alon Barsheshet, Bela Merkely, Axel Kloppe, Arthur Moss, Ilan Goldenberg
Journal: Journal of the American College of Cardiology (2012)
Attentional Functioning in Children and Adolescents With IDDM
Authors: Joanne Rovet, Miguel Alvarez
Journal: Diabetes Care (1997)

To determine whether specific attentional cognitive processes are disrupted in children and adolescents with IDDM.We tested 103 children and adolescents with IDDM and 100 healthy control subjects (age range 9.3-18.3 years) for intelligence and attention. Subjects were given multiple clinical tests of attention and a computerized vigilance test, all of which served to provide information about multiple components of attentional processing. Specific components studied were the abilities to focus, select, shift, suppress, inhibit, and sustain attention. A diabetic history was obtained for the IDDM group, and blood glucose levels were determined before and after computerized attention testing.Across tests, IDDM subjects differed from control subjects only in the select component of attention, which was accounted for mainly by the poorer performance of children with early-onset diabetes (< 6 years). When subgrouped by history of seizures from hypoglycemia, those having had seizures demonstrated a lower verbal IQ and greater difficulty with select, focus, and inhibit attentional components, whereas sustain, suppress, and shift attentional components were unaffected. Correlation analyses showed that higher concurrent blood glucose levels were associated with less adequate ability to inhibit impulsive responses, whereas multiple regression analyses indicated that inhibit and focus were best predicted by onset age and concurrent blood glucose.In children and adolescents with IDDM, attention is poorer in several but not all aspects of attention; these aspects are affected by a history of seizures from hypoglycemia and higher ambient blood glucose levels at time of testing. These results suggest both organizational and activational effects of diabetes on specific subcomponents of attention in diabetes.
Induction of apoptosis in catecholaminergic PC12 cells by L-DOPA. Implications for the treatment of Parkinson's disease.
Authors: G Walkinshaw, C M Waters
Journal: Journal of Clinical Investigation (1995)

The hypothesis that L-DOPA therapy in Parkinson's disease may augment neuronal damage and thus accelerate the progression of the disease remains controversial. In this study, we demonstrate that L-DOPA induces death of catecholaminergic cells in vitro via an active program of apoptosis. Treatment of PC12 cells with clinically applicable concentrations of L-DOPA (25-100 microM) induced cell death via a mechanism which exhibited morphological and biochemical characteristics of apoptosis, including chromatin condensation, membrane blebbing, and internucleosomal DNA fragmentation. L-DOPA-induced apoptosis was cell and drug-type specific. Toxicity is an intrinsic property of the drug molecule since it was not suppressed by inhibiting conversion of L-DOPA to dopamine. However, L-DOPA toxicity was inhibited by antioxidants, suggesting that activation of apoptosis is mediated by oxygen radicals. Our finding that L-DOPA-induced cell death in vitro occurs via apoptosis explains the lack of evidence supporting its toxicity in vivo, since apoptotic neurons are rapidly phagocytosed in vivo without causing damage to surrounding tissue. Furthermore, since apoptosis is an active cellular program which can be modulated, we suggest clinical approaches for decreasing L-DOPA toxicity, thus preventing acceleration of neuronal damage in Parkinson's disease.
Polish police hold health workers over alleged murder of patients
Authors: K. Krosnar
Journal: BMJ (2002)

Polish police have detained seven people including doctors and paramedics on suspicion of being involved in a scam in which patients were killed and their bodies sold to undertakers.

They are investigating claims that ambulance crews in Lodz, 110 km from Warsaw, deliberately delayed the arrival of emergency vehicles at patients' homes or at hospitals, leaving patients to die, and even administered drugs that speeded up the deaths of seriously ill patients, in return for bribes. It is thought the practice could have been going on for years and that hundreds …
Abstract 5350: Aldehyde dehydrogenase 1 is useful for identifying some subtypes of non-basal triple negative breast cancer
Authors: Takashi Ishikawa, Yashushi Ichikawa, Daisuke Shimizu, Akimitsu Yamada, Mikiko Tanabe, Takeshi Sasaki, Kumiko Kida, Mariko Kimura, Ikuko Ota, Takashi Chishima, Itaru Endo
Journal: Cancer Research (2012)

Abstract BACKGROUND Triple negative breast cancer (TNBC) is heterogeneous and consists of tumors associated with basal-type and cancer stem cell (CSC) phenotypes. Identifying these specific phenotypes is important for treating TNBC. The expression of aldehyde dehydrogenase 1 (ALDH-1), a biomarker of CSC phenotype, is observed more frequently in TNBC than non-TNBC and is associated with biologically aggressive features. AIM In order to categorize types of breast cancer, especially TNBC, ALDH-1 was examined in terms of 1) its association with pathological factors and 2) the genes significantly expressed in ALDH-1 positive cells. METHODS 1) The expression of ALDH-1 and its association with the other pathological factors of ER, PgR, HER2, p53, Ki-67, CK5/6, EGFR were examined immunohistochemically in 87 breast cancer samples. Histological grade was assigned to each of the samples.2) ALDH-1 positive and negative cells were collected by microdissection from formalin-fixed paraffin- embedded samples of 5 ALDH-1 positive breast cancer cases. mRNA was extracted and the expression profile of approximately 5,000 genes was assessed by cDNA microarray (Affymetrix GeneChip®, Human Genome U133 Plus 2.0 Array). By comparing gene expressions of ALDH-1 positive and negative cells in the same sample, characteristic genes related to CSC were identified. RESULTS 1) ALDH-1 was inversely correlated with ER (p=0.0006) and PgR (p=0.0054), while positively correlated with Ki67 (p=0.0023) and TopoII (p=0.0014). No association was found between ALDH-1 with CK5/6 or with EGFR. 2) Approximately 800 annotated genes were significantly up- or down- regulated. Several characteristic genes related to ALDH-1 have been presently confirmed by other methodologies. CONCLUSION CK5/6 and EGFR are currently used to identify basal-type TNBC. Because ALDH-1 was not associated with CK5/6 or EGFR, ALDH-1 and related genes may be helpful in identifying some non-basal types of TNBC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5350. doi:1538-7445.AM2012-5350
An osteopenic nonfracture syndrome with features of mild osteogenesis imperfecta associated with the substitution of a cysteine for glycine at triple helix position 43 in the pro alpha 1(I) chain of type I collagen.
Authors: J R Shapiro, M L Stover, V E Burn, M B McKinstry, A L Burshell, S D Chipman, D W Rowe
Journal: Journal of Clinical Investigation (1992)

Mutations affecting the pro alpha 1(I) or pro alpha 2(I) collagen genes have been identified in each of the major clinical types of osteogenesis imperfecta. This study reports the presence of a heritable connective tissue disorder in a family with an osteopenic syndrome which has features of mild osteogenesis imperfecta but was considered idiopathic osteoporosis in the proband. At age 38, while still premenopausal, she was found to have osteopenia, short stature, hypermobile joints, mild hyperelastic skin, mild scoliosis, and blue sclerae. There was no history of vertebral or appendicular fracture. Hip and vertebral bone mineral density measurements were consistent with marked fracture risk. Delayed reduction SDS-PAGE of pepsin-digested collagens from dermal fibroblast cultures demonstrated an anomalous band migrating between alpha 1(I) and alpha 1(III). This band merged with the normal alpha-chains upon prereduction, indicating an unexpected cysteine residue. Cyanogen bromide peptide mapping suggested that the mutation was in the smaller NH2-terminal peptides. cDNA was reverse transcribed from mRNA and amplified by the polymerase chain reaction. A basepair mismatch between proband and control alpha 1(I) cDNA hybrids was detected by chemical cleavage with hydroxylamine:piperidine. The cysteine substitution was thus localized to alpha 1(I) exon 9 within the cyanogen bromide 4 peptide. Nucleotide sequence analysis localized a G----T point mutation in the first position of helical codon 43, replacing the expected glycine (GGT) residue with a cysteine (TGT). The prevalence of similar NH2-terminal mutations in subjects with this phenotype which clinically overlaps idiopathic osteoporosis remains to be determined.
Maturing reticulocytes internalize plasma membrane in glycophorin A–containing vesicles that fuse with autophagosomes before exocytosis
Authors: Rebecca E. Griffiths, Sabine Kupzig, Nicola Cogan, Tosti J. Mankelow, Virginie M. S. Betin, Kongtana Trakarnsanga, Edwin J. Massey, Jon D. Lane, Stephen F. Parsons, David J. Anstee
Journal: Blood (2012)
Thallium-201 and Gallium-67 Myocardial Scintigraphy for the Evaluation of Sarcoid Involvement
Authors: YOSHITATSU NAGATOMO, TAKUROH IMAMURA, YASUSHI KOIWAYA, SEISHI JINNOUCHI, HIROAKI HOSHI, KATSUSHI WATANABE, KENJIRO TANAKA
Journal: Clinical Nuclear Medicine (1987)

In a patient with cardiac sarcoidosis, left ventriculography demonstrated asynergy on the antero-lateral and infero-apical wall. TI-201 myocardial scintigraphy revealed a perfusion defect on the portion compatible with the asynergic area, however, Ga-67 scintigram showed only antero-lateral uptake. The matching and mismatching of both scintigrams may be useful in evaluating the location and grading of myocardial sarcoid involvement.
CATARACT EXTRACTION.I. IS THE CASE OPERABLE? II. PREPARATION OF THE PATIENT. III. THE ANESTHETIC.
Authors: EDWIN E. JACK
Journal: JAMA (1907)

<h3>I. IS THE CASE OPERABLE?</h3> In opening this subject I fear that I have little to give that is new or even interesting. The question whether a case is operable must be decided from three standpoints—that of the general health of the patient, the condition of the eye and its surroundings and the state of the cataract itself. There has been, as far as I know, but little recent change in the accepted views on these points. Chronic heart, lung and kidney disease and diabetes are no longer considered bars to operation, provided the patient is put into the best general condition which his disease will permit, and also provided, of course, that this condition justifies the operation. Coughing reduced by treatment to a minimum, the inability to lie down in bed and other necessary concomitants of the diseases mentioned are not as important as the estimate of the general
Evolution of genomic instability in diethylnitrosamine-induced hepatocarcinogenesis in mice
Authors: Kristina Aleksic, Carolin Lackner, Jochen B. Geigl, Martina Schwarz, Martina Auer, Peter Ulz, Maria Fischer, Zlatko Trajanoski, Marcus Otte, Michael R. Speicher
Journal: Hepatology (2010)

Abstract Diethylnitrosamine (DEN) is a hepatic procarcinogen which is frequently used as an inducer of hepatocellular carcinoma (HCC) in mice. Although mice after DEN exposure are among the most widely used models for liver tumorigenesis, a detailed, mechanistic characterization of the longitudinal changes in the respective tumor genomes has never been performed. Here we established the chronological order of genetic alterations during DEN carcinogenesis by examining mice at different points in time. Tumor samples were isolated by laser microdissection and subjected to array-comparative genomic hybridization (array-CGH) and sequencing analysis. Chromosomal gains and losses were observed in tumors by week 32 and increased significantly by week 56. Loss of distal chromosome 4q, including the tumor suppressors Runx3 and Nr0b2/Shp , was a frequent early event and persisted during all tumor stages. Surprisingly, sequencing revealed that β-catenin mutations occurred late and were clearly preceded by chromosomal instability. Thus, contrary to common belief, β-catenin mutations and activation of the Wnt/β-catenin pathway are not involved in tumor initiation in this model of chemical hepatocarcinogenesis. Conclusion: Our study suggests that the majority of the current knowledge about genomic changes in HCC is based on advanced tumor lesions and that systematic analyses of the chronologic order including early lesions may reveal new, unexpected findings. (Hepatology 2011;)
Nucleocytosolic Depletion of the Energy Metabolite Acetyl-Coenzyme A Stimulates Autophagy and Prolongs Lifespan
Authors: Tobias Eisenberg, Sabrina Schroeder, Aleksandra Andryushkova, Tobias Pendl, Victoria Küttner, Anuradha Bhukel, Guillermo Mariño, Federico Pietrocola, Alexandra Harger, Andreas Zimmermann, Tarek Moustafa, Adrian Sprenger, Evelyne Jany, Sabrina Büttner, Didac Carmona-Gutierrez, Christoph Ruckenstuhl, Julia Ring, Wieland Reichelt, Katharina Schimmel, Tina Leeb, Claudia Moser, Stefanie Schatz, Lars-Peter Kamolz, Christoph Magnes, Frank Sinner, Simon Sedej, Kai-Uwe Fröhlich, Gabor Juhasz, Thomas R. Pieber, Jörn Dengjel, Stephan J. Sigrist, Guido Kroemer, Frank Madeo
Journal: Cell Metabolism (2014)

Healthy aging depends on removal of damaged cellular material that is in part mediated by autophagy. The nutritional status of cells affects both aging and autophagy through as-yet-elusive metabolic circuitries. Here, we show that nucleocytosolic acetyl-coenzyme A (AcCoA) production is a metabolic repressor of autophagy during aging in yeast. Blocking the mitochondrial route to AcCoA by deletion of the CoA-transferase ACH1 caused cytosolic accumulation of the AcCoA precursor acetate. This led to hyperactivation of nucleocytosolic AcCoA-synthetase Acs2p, triggering histone acetylation, repression of autophagy genes, and an age-dependent defect in autophagic flux, culminating in a reduced lifespan. Inhibition of nutrient signaling failed to restore, while simultaneous knockdown of ACS2 reinstated, autophagy and survival of ach1 mutant. Brain-specific knockdown of Drosophila AcCoA synthetase was sufficient to enhance autophagic protein clearance and prolong lifespan. Since AcCoA integrates various nutrition pathways, our findings may explain diet-dependent lifespan and autophagy regulation.
Update in Oncology
Authors: John C. Ruckdeschel
Journal: Annals of Internal Medicine (1999)

Updates from the Annual Session16 November 1999Update in OncologyJohn C. Ruckdeschel, MDJohn C. Ruckdeschel, MDFrom H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-10-199911160-00008 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Among the many important topics that currently come under the heading of oncology—from cell markers to molecular biology factors—this Update focuses on the most common diseases: prostate cancer, breast cancer, and lung cancer. Table 1 spells out the statistics on these diseases and makes an important point about survival.Table 1. Cancer Incidence Prostate CancerThe main questions that are being asked and now answered about prostate cancer are the following: Who is at risk? Can the disease be diagnosed early? Does early diagnosis improve survival? What is the optimal therapy? The articles described here highlight ... Author, Article, and Disclosure InformationAuthors: John C. Ruckdeschel, MDAffiliations: From H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.Corresponding Author: John C. Ruckdeschel, MD, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612-9497. For reprint orders in quantities exceeding 100, please contact the Reprints Coordinator; phone, 215-351-2657; e-mail, [email protected]acponline.org. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 November 1999Volume 131, Issue 10Page: 760-767KeywordsBreast cancerChemotherapyComputed axial tomographyDisease free survivalLung and intrathoracic tumorsLymph nodesProstate cancerRadiation therapyRadical prostatectomySurgery ePublished: 15 August 2000 Issue Published: 16 November 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Increased secretion of tumor necrosis factor-alpha and interferon-gamma by mononuclear leukocytes in patients with ischemic heart disease. Relevance in superoxide anion generation.
Authors: K Vaddi, F A Nicolini, P Mehta, J L Mehta
Journal: Circulation (1994)

BACKGROUND There is growing evidence for a pathogenic role for cytokines in atherogenesis. The presence of certain cytokines has been documented in human atherosclerotic vessels. This study was designed to investigate cytokine production by mononuclear leukocytes from patients with ischemic heart disease. METHODS AND RESULTS We measured kinetics of secretion of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) by mononuclear leukocytes from 8 control subjects, 10 patients with stable angina pectoris, and 10 patients with unstable angina pectoris. Mononuclear leukocytes were isolated and incubated with or without the plant lectin mitogen concanavalin A for 48 hours. TNF-alpha and IFN-gamma secretion were measured by ELISA. The effect of TNF-alpha and IFN-gamma on superoxide radical generation by neutrophils was also examined. Secretion of both TNF-alpha and IFN-gamma by mononuclear leukocytes increased progressively over 48 hours, and it was consistently higher (P &lt; .02) in patients compared with control subjects. A similar increase in cytokine secretion was observed in patients with stable or unstable angina pectoris. In addition, there was no relation between the severity of coronary artery disease by angiography and cytokine secretion. Basal neutrophil superoxide radical generation was increased in patients with ischemic heart disease, and incubation with cytokines failed to further stimulate superoxide generation in these patients. CONCLUSIONS Similar increases in cytokine secretion by mononuclear leukocytes in stable or unstable angina pectoris indicate that the increased cytokine release is not a nonspecific inflammatory response in acute myocardial ischemia. Increased cytokine secretion in ischemic heart disease may play a role in superoxide radical generation, endothelial injury, deposition and activation of cellular elements on the vessel wall, and possibly in the progression of atherosclerosis.
Abstract B12: Molecular mechanisms of HIF-1a and HIF-2a activation in nonmalignant cells at the premetastatic niche: Effects on metastatic success
Authors: Cristina Branco-Price, Asis Palazon, Jessica Xie, Randall S. Johnson
Journal: Cancer Research (2015)

Abstract Tumor hypoxia and the hypoxia-inducible transcription factors (HIF) have been thoroughly characterized in solid tumors, and they are active participants in pathways promoting tumor growth and dispersion. However, despite their well-known pro-tumorigenic role when stabilized in cancer cells, HIF activation in other cell types has been shown to be less consistent and often antagonistic. We have previously shown that specific deletion of HIF-1a in endothelial cells results in reduced tumor cell migration and metastatic incidence, whereas deletion of HIF-2a in this same cell type has the opposite effect. This phenomenon also involved endothelial-specific nitric oxide production via the inducible NOS (iNOS). Endothelial cells are at the interface between the primary tumor and the rest of the body, and play a role not only in tumor maintenance and growth, but also in metastatic success and proliferation at secondary sites. Immune/inflammatory cells are also known to be active players in tumor cell motility and establishment. We are interested in understanding the role of non-malignant cell types in the metastatic process, specifically (i) signals that trigger HIF-1a or HIF-2a activation at metastatic sites and (ii) how does the stabilization of either HIF isoform (or both) affect tumor cell recruitment and establishment. This work uses primary cells isolated from different genotypic backgrounds to dissect the hypoxia-response regulatory pathways, using a combination of screenings: transcription factor activation and downstream transcriptional targets, in order to build a map of HIF-dependent metabolism. Specifically, we are interested in the pathways which activation or silencing could have an effect on vascular morphology, permeability, inter-cellular signaling and post-extravasation events. Complementary studies in physiological models of extravasation were used for histological, molecular and biochemical analysis of hypoxic tissue to study molecular players identified by our initial ex-vivo screening. Citation Format: Cristina Branco-Price, Asis Palazon, Jessica Xie, Randall S. Johnson. Molecular mechanisms of HIF-1a and HIF-2a activation in nonmalignant cells at the premetastatic niche: Effects on metastatic success. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr B12. doi:10.1158/1538-7445.CHTME14-B12