tbuckley/cabot-search huggingface dataset:
Binding of Human IgG to Cultured Urogenital Tumor Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G L Wright, M L Beckett, A E Campbell, K G Gardner, K D Somers
Journal: JNCI Journal of the National Cancer Institute (1987)

Binding of human IgG by the Fc portion of the immunoglobulin molecule was detected on established human tumor cell lines by indirect immunofluorescence microscopy, cytofluorography, quantitative absorption, and rosette formation with the use of antibody-coated erythrocytes. Of the nonlymphoid tumors tested, IgG binding was restricted to the cell membranes of certain prostate and urinary bladder tumor cell lines. Although most cell lines tested shared a common antigenic determinant with monocytes and granulocytes, these cells did not express T- and B-cell antigens, the complement 3b receptor, or bind a monoclonal antibody specific for the Fc receptor expressed on human neutrophils. The facts that IgG binding was present on long-term established tumor lines and was not influenced by in vitro passage provide evidence that these properties are intrinsic to the tumor cells and may play some role in the pathophysiology of these tumors.
iPSC-derived mesenchymal stromal cells are less supportive than primary MSCs for co-culture of hematopoietic progenitor cells
Authors: Theresa Vasko, Joana Frobel, Richard Lubberich, Tamme W. Goecke, Wolfgang Wagner
Journal: Journal of Hematology & Oncology (2016)

In vitro culture of hematopoietic stem and progenitor cells (HPCs) is supported by a suitable cellular microenvironment, such as mesenchymal stromal cells (MSCs)—but MSCs are heterogeneous and poorly defined. In this study, we analyzed whether MSCs derived from induced pluripotent stem cells (iPS-MSCs) provide a suitable cellular feeder layer too. iPS-MSCs clearly supported proliferation of HPCs, maintenance of a primitive immunophenotype (CD34+, CD133+, CD38-), and colony-forming unit (CFU) potential of CD34+ HPCs. However, particularly long-term culture-initiating cell (LTC-IC) frequency was lower with iPS-MSCs as compared to primary MSCs. Relevant genes for cell-cell interaction were overall expressed at similar level in MSCs and iPS-MSCs, whereas VCAM1 was less expressed in the latter. In conclusion, our iPS-MSCs support in vitro culture of HPCs; however, under the current differentiation and culture conditions, they are less suitable than primary MSCs from bone marrow.
Abstract 18329: Aortic Pulse Wave Velocity Improves Following Moderate-intensity Continuous Training but not High-intensity Interval Training in Older Men and Postmenopausal Women
Authors: Han-Kyul Kim, Chueh-Lung Hwang, Jeung-Ki Yoo, Moon-Hyon Hwang, Eileen M Handberg, Wilmer W Nichols, Demetra D Christou
Journal: Circulation (2015)

Introduction: Aortic pulse wave velocity (AoPWV), a measure of arterial stiffness, increases with age and is an independent predictor of cardiovascular disease. Higher levels of habitual physical activity are associated with reduced AoPWV, but the effect of well-controlled aerobic training interventions in healthy older adults remains unclear. We hypothesized that moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) will both improve AoPWV in healthy older adults. Methods: Thirty five sedentary older men and postmenopausal women, free of overt cardiovascular disease (age, 65±1 yrs, body mass index, 27.7±0.8 kg/m 2 ; systolic and diastolic blood pressures, 116±2 and 69±1 mmHg, respectively; mean±SE) participated in this intervention. Subjects were randomized to MICT (n=13), HIIT (n=12) or non-exercise control group (CONT; n=10). Isocaloric MICT and HIIT were performed on Airdyne bicycles 4 days/week for 8 weeks under supervision. MICT consisted of 47 min of cycling at 70% of maximal heart rate, while HIIT consisted of 40 min of cycling at alternating intensities of 90% and 70% of maximal heart rate. AoPWV, aortic systolic and diastolic blood pressures were evaluated using applanation tonometry (SphygmoCor) before and after the intervention. Results: AoPWV improved by 0.52 m/s in MICT (9.26±0.39 vs. 8.75±0.35 m/s, pre- vs. post-intervention; P&lt;0.05), but did not change in HIIT (9.29±0.29 vs. 9.16±0.38 m/s, P&gt;0.05) or CONT (8.82±0.75 vs. 9.26±0.70 m/s, P&gt;0.05). Aortic systolic blood pressure (MICT: 106±2 vs. 107±3 mmHg; HIIT: 115±3 vs. 113±4 mmHg; CONT: 109±5 vs. 110±4 mmHg) and diastolic blood pressure (MICT: 69±2 vs. 69±2 mmHg; HIIT: 70±2 vs. 70±2 mmHg; CONT: 68±2 vs. 69±2 mmHg) did not change with the intervention (P&gt;0.05). Body mass index remained unchanged in all groups (P&gt;0.05). Conclusions: MICT Airdyne exercise leads to arterial destiffening, however, HIIT does not lead to improved arterial stiffness in healthy older men and postmenopausal women.
HCP-04THE UK TOP TEN CLINICAL RESEARCH PRIORITY QUESTIONS IN NEURO-ONCOLOGY
Authors: Helen Bulbeck, Robin Grant, Julia Day, Laura Macdonald, Richard Morley, Kathy Oliver, Gail Quinn
Journal: Neuro-Oncology (2015)

INTRODUCTION: Many clinical questions about brain and spinal cord tumours remain unanswered. Objectives of the Neuro-Oncology Priority Setting Partnership (PSP) were: To identify the top 10 treatment uncertainties in diagnosis and management of primary central nervous system (CNS) tumours; To highlight the necessity of a brain tumour community collaborative approach to priority setting in clinical research; To encourage other countries to use the PSP methodology to draw international comparisons. METHOD: 30 stakeholder representatives from a cross section of the UK brain tumour community were recruited. The scope was: clinical uncertainties of interventions for primary brain or spinal cord tumours. The first public survey was widely publicised by websites, MDMs, professional and charity databases. Questions were categorised and standardised into the PICO format. A Cochrane style literature search was performed to ensure these were genuine “uncertainties”. Initial prioritisation used standard James Lind Alliance (JLA) methodology. A second public survey was performed using the prioritised questions, to ask the community to rate the questions. A final workshop determined the top 10 questions using a modified Delphi and Nominal Group technique. RESULTS: Over 600 individual questions were generated from the initial survey, a patient forum and the Database of Treatment Uncertainties (DUETS). These were analysed and reduced to 44 PICO questions. These were sent out in a second public survey. The penultimate group of 25 questions was discussed at a final workshop, reaching agreement on the final top 10 uncertainties. CONCLUSION: To focus attention on what really matters to those affected by brain and spinal cord tumours, it is crucial to promote the 10 clinical research uncertainties (http://www.neuro-oncology.org.uk) to governmental, neuroscience and charity funders throughout 2015/16. This has been a very successful and rewarding joint collaboration between CNS patients/carers, major charities and multidisciplinary professional organisations.
Case 2-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert I. Handin, Michael Laposata
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 72-year-old woman was admitted to the hospital because of swelling and ecchymoses of both lower extremities and anemia.The patient was in excellent health until five weeks earlier, when pain and swelling developed in the right leg. A physician diagnosed superficial thrombophlebitis and prescribed aspirin and rest. The aspirin was discontinued after two weeks because of the development of bruises over the arms and face. Three and a half weeks before entry the left leg began to swell progressively.Eleven days before admission the patient was admitted to another hospital. The hematologic and blood chemical findings . . .
Is there a rationale for rationing chronic dialysis?
Authors: R. Ahmad, T Farrant, F. J Caskey, W. Metcalfe, A. M MacLeod, I. H Khan, S. M Chandna, R. N Greenwood, K. Farrington
Journal: BMJ (1999)

# Two points need clarification {#article-title-2} EDITOR—I agree with Chandna et al that late referral is an important factor in the survival of patients receiving dialysis.1 I am unaware, however, of the source of their information that an NHS consensus statement recommends that nephrology referrals be made at a serum creatinine concentration >135 μmol/l in women and >180 μmol/l in men. The workload generated by this practice would be so enormous that British renal units under present conditions would be unable to cope. I am also concerned that of the authors' 292 patients receiving dialysis, 26 (admittedly high risk) patients spent 44% of their lives in hospital. The costs of inpatient treatment for these high risk patients would be substantially higher than the average cost of £250 a day that the authors quote. 1. ↵1. Chandna SM, 2. Schulz J, 3. Lawrence C, 4. Greenwood RN, 5. Farrington K .Is there a rationale for rationing chronic dialysis? A hospital based cohort study of factors affecting survival and morbidity.BMJ1999; 318:217–223. (23 January.) [OpenUrl][1][Abstract/FREE Full Text][2] # Study's objectives were not achieved {#article-title-4} EDITOR—Chandna et al's study asking whether there is a rationale for rationing chronic dialysis does not fulfil its stated purpose.1 The study successfully shows the groups of patients already receiving dialysis who could be expected to do poorly, and this might be used as a rationale for withdrawing treatment in this small group. The cost savings that their unit would accrue are nevertheless small (just 3.2% of the cost of their chronic dialysis programme). Even in the authors' high risk group five of the 26 patients were long term survivors. This is similar to the effect of interferon treatment in hepatitis C in terms of long term response and better than results of in vitro fertilisation programmes. One could … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DChandna%26rft.auinit1%253DS.%2BM%26rft.volume%253D318%26rft.issue%253D7178%26rft.spage%253D217%26rft.epage%253D223%26rft.atitle%253DIs%2Bthere%2Ba%2Brationale%2Bfor%2Brationing%2Bchronic%2Bdialysis%253F%2BA%2Bhospital%2Bbased%2Bcohort%2Bstudy%2Bof%2Bfactors%2Baffecting%2Bsurvival%2Band%2Bmorbidity%26rft_id%253Dinfo%253Adoi%252F10.1136%252Fbmj.318.7178.217%26rft_id%253Dinfo%253Apmid%252F9915728%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=bmj&resid=318/7178/217&atom=%2Fbmj%2F318%2F7198%2F1619.atom
Sleep Apnea -- A Major Public Health Problem
Authors: Eliot A. Phillipson
Journal: New England Journal of Medicine (1993)

The National Commission on Sleep Disorders Research was established by Congress in 1988 “to conduct a comprehensive study of sleep disorders and to develop a long-range plan for the use and organization of national resources to deal effectively with sleep disorders research and medicine”1. The report of the commission, which was recently published,1 indicates that each year the lives of millions of Americans are disturbed, disrupted, or destroyed by the consequences of sleep disorders.Among specific sleep disorders, the most serious in terms of morbidity and mortality is obstructive sleep apnea2. This disorder is characterized by recurrent episodes . . .
Nonsteroidal anti-inflammatory drugs (NSAIDs) or EP4 receptor antagonism enhances hematopoietic stem and progenitor cell (HSPC) mobilization and facilitates faster hematopoietic recovery after myeloablation.
Authors: J. Hoggatt, P. Singh, A. Hoggatt, J. M. Speth, L. M. Pelus
Journal: Journal of Clinical Oncology (2010)

6604 Background: We recently reported that Prostaglandin E2 (PGE2) increases homing and engraftment of HSPC to bone marrow (Hoggatt et al, Blood 2009). We hypothesized that blocking PGE2 synthesis via inhibition of cyclooxygenases (COX) by NSAIDs would facilitate HSPC mobilization and serve as an adjunct to current mobilization regimens. Methods: Mice were treated with filgrastim (Neupogen) (FG) with or without co-administration of NSAID or specific agonists and antagonists of PGE2 receptors (EP1-4). HSPC mobilized to peripheral blood were quantitated by colony forming units-granulocyte/macrophage (CFU-GM), by flow cytometry, or in competitive transplantation assays. In addtion, to confirm in a non-human primate model, 4 baboons were mobilized with FG ± NSAID in a crossover protocol. Results: Treatment of mice with NSAID + FG resulted in an increase in CFU-GM over FG alone (1.96 ± 0.19 fold, p < 0.001). NSAID synergistically enhanced mobilization by plerixafor (Mozobil) alone or with GROβ, indicating FG-independent mechanisms. In baboons, NSAID increased CFU-GM (2,845 vs. 5,975, p = 0.03) and CD34+ cells (9,051 vs. 2,6910, p = 0.03) per ml blood. Lethally irradiated mice transplanted with FG + NSAID mobilized grafts exhibited faster recovery of both neutrophils and platelets, with an increase in competitive repopulating units, indicating long-term repopulating cells were mobilized. EP4 antagonists significantly enhanced mobilization (2.02 ± 0.21 fold, p < 0.005), while an EP1-3 antagonist had no effect. Similarly, an EP4 agonist abrogated NSAID enhancement, while EP1-3 agonists did not, indicating that a lack of EP4 receptor signaling is responsible for enhanced HSPC mobilization. Conclusions: Our results define a novel role for NSAIDs and suggest that addition of NSAIDs, particularly Meloxicam, to current mobilization regimens may increase HSPC yield. In addition, we have identified novel mechanisms mediated by EP receptors and show that mobilization can be enhanced through antagonism of the EP4 receptor, defining a new pharmaceutical target for hematopoietic mobilization and transplantation. No significant financial relationships to disclose.
Production of Lymphotoxin, a Bone-Resorbing Cytokine, by Cultured Human Myeloma Cells
Authors: I. Ross Garrett, Brian G.M. Durie, Glenn E. Nedwin, Alison Gillespie, Timothy Bringman, Massimo Sabatini, Donald R. Bertolini, Gregory R. Mundy
Journal: New England Journal of Medicine (1987)

Myeloma cells destroy bone by producing an osteoclast-stimulating factor that has chemical and biological characteristics similar to the bone-resorbing activity present in the supernatants of activated leukocyte cultures. Recently, a number of bone-resorbing leukocyte cytokines have been identified, including interleukin-1, lymphotoxin, and tumor necrosis factor. We have examined the products of human myeloma cells for the presence of these bone-resorbing cytokines. In a tumor cell line derived from a patient who had myeloma with osteolytic bone lesions and hypercalcemia, we found that the myeloma cells induced bone-resorbing activity and cytotoxic activity in vitro. Most of the bone-resorbing activity and all cytotoxic activity were suppressed by neutralizing antibodies to lymphotoxin. The myeloma cells expressed both lymphotoxin and tumor necrosis factor mRNA, but no tumor necrosis factor could be detected in the cell-culture medium. Interleukin-1 mRNA was not detected in the myeloma cells, and biologic activity of interleukin-1 was not measurable in the medium harvested from the cultured cells. The bone-resorbing activity induced by recombinant tumor necrosis factor and recombinant interleukin-1 was not affected by treatment with the lymphotoxin antibodies. When lymphotoxin was infused subcutaneously into normal mice (10 μg per day for three days), their plasma calcium levels increased. We also evaluated four established cell lines derived from three other patients with myeloma, and found a similar pattern of lymphotoxin expression in each. It appears that production of the bone-resorbing cytokine lymphotoxin is related to osteoclastic bone destruction and hypercalcemia in patients with myeloma. (N Engl J Med 1987;317:526–32.)
Association of the single nucleotide polymorphism TNRC9 rs3803662 on mammographic density and estrogen receptor-positive breast cancer risk in Japanese women.
Authors: Nobuyasu Yoshimoto, Takeshi Nishiyama, Hiroko Yamashita, Satoru Takahashi, Norio Shiraki, Hiroshi Sugiura, Yumi Endo, Mai Iwasa, Tomoko Asano, Yukari Hato, Yoshitaka Fujii, Tatsuya Toyama
Journal: Journal of Clinical Oncology (2014)

1523 Background: The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades. We recently created risk prediction models for estrogen receptor (ER)-positive breast cancer in both pre- and post- menopausal women using genetic factors (single nucleotide polymorphisms (SNPs)), environmental risk factors, serum hormones and growth factors, by logistic regression analysis. However, mammographic density is also considered to be a risk factor for breast cancer. To acquire some insight into the relationships among SNPs, mammographic density and breast cancer risk, we analyzed the correlation between these factors. Methods: The study population comprised 913 consecutive Japanese women with breast cancer, and 278 control Japanese women. We analyzed the correlation between genetic factors (14 SNPs) and breast cancer risk in both premenopausal and postmenopausal women. We also analyzed differences in mammographic density between the SNP genotypes (homozygotes of major alleles, heterozygotes and homozygotes of minor alleles) in the combined population of both premenopausal and postmenopausal women. Results: CYP19A1 rs10046 TT genotype and TNRC9 rs3803662 AA genotype were both found to have a significant association with ER-positive breast cancer in premenopausal women (OR 0.55: P = 0.019, OR 1.59: P = 0.027), while ESR1 rs6905370 GG genotype and TP53 rs1042522 CC genotype were significantly associated with ER-positive breast cancer in postmenopausal women (OR 1.83: P = 0.033, OR 0.54: P = 0.045). Mammographic density differed significantly among CYP2C19 rs4917623 genotypes (CC 50.23 +/- 18.82%, CT 46.69 +/- 20.03%, TT 49.04 +/- 19.22%, P = 0.009), among ESR1 rs827421 genotypes (AA 49.97 +/- 20.77%, AG 47.63 +/- 18.51%, GG 45.19 +/- 19.20%, P = 0.048) and among TNRC9 rs3803662 genotypes (AA 49.35 +/- 18.43%, AG 48.43 +/- 20.45%, GG 44.12 +/- 18.41%, P= 0.026). Conclusions: TRNC9 rs3803662 AA genotype was considered to confer an increased risk of ER-positive breast cancer by increasing mammographic density. ESR1 rs827421 AA genotype might also increase ER-positive breast cancer risk by the same mechanism.
Case 10-2009
Authors: Mark A. Goldstein, Annekathryn Goodman, Marcela G. del Carmen, David C. Wilbur
Journal: New England Journal of Medicine (2009)

A 23-year-old woman came to the adolescent and young adult medicine clinic at this hospital to establish care and to receive counseling regarding oral contraception, screening for sexually transmitted infections, and vaccination against human papillomavirus. Pathological examination of a Papanicolaou smear disclosed a high-grade squamous intraepithelial lesion. Additional diagnostic testing was performed, and management decisions were made.
A Phase 1 Mechanism of Action Study of Intra-Tumoural (It) or Intravenous (Iv) Administration of Enadenotucirev, an Oncolytic Ad11/Ad3 Chimeric Group B Adenovirus in Colon Cancer Patients Undergoing Resection of Primary Tumour
Authors: V. Boni, F. De La Portilla, A. Cubillo, M. Gil-Martin, E. Calvo, R. Salazar, C. Santos, A. Sanchez-Gastaldo, S. Prados, X. Sanjuan, J.M. Bozada, H. Duran, M. Jurado, C. Ellis, S. Alvis, J. Beadle, K. Fisher, C. Blanc, R. Garcia-Carbonero
Journal: Annals of Oncology (2014)
Elevated blood serotonin concentrations in unmediated chronic schizophrenic patients: a preliminary study
Authors: E Garelis, J C Gillin, R J Wyatt, N Neff
Journal: American Journal of Psychiatry (1975)

The authors found higher serotonin concentrations in the blood of unmedicated chronic schizophrenic patients than in the blood of medicated schizophrenic patients or normal control subjects. This finding is consistent with the previous observation that the level of monoamine oxidase activity is low in the platelets of chronic schizophrenics.
Correction of X-Linked Hyper-IgM Syndrome by Allogeneic Bone Marrow Transplantation
Authors: Caroline Thomas, Geneviève de Saint Basile, Françoise Le Deist, Didier Theophile, Malika Benkerrou, Elie Haddad, Stéphane Blanche, Alain Fischer
Journal: New England Journal of Medicine (1995)

The X-linked hyper-IgM syndrome is a rare immunodeficiency disease in which the ability of B cells to switch immunoglobulin production from IgM to IgG, IgA, and IgE is defective.1 A variety of muta...
Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma
Authors: Kensuke Tateishi, A. John Iafrate, Quan Ho, William T. Curry, Tracy T. Batchelor, Keith T. Flaherty, Maristela L. Onozato, Nina Lelic, Sudhandra Sundaram, Daniel P. Cahill, Andrew S. Chi, Hiroaki Wakimoto
Journal: Clinical Cancer Research (2016)

Deregulated Myc drives an oncogenic metabolic state, including pseudohypoxic glycolysis, adapted for the constitutive production of biomolecular precursors to feed rapid tumor cell growth. In glioblastoma, Myc facilitates renewal of the tumor-initiating cell reservoir contributing to tumor maintenance. We investigated whether targeting the Myc-driven metabolic state could be a selectively toxic therapeutic strategy for glioblastoma.The glycolytic dependency of Myc-driven glioblastoma was tested using (13)C metabolic flux analysis, glucose-limiting culture assays, and glycolysis inhibitors, including inhibitors of the NAD(+) salvage enzyme nicotinamide phosphoribosyl-transferase (NAMPT), in MYC and MYCN shRNA knockdown and lentivirus overexpression systems and in patient-derived glioblastoma tumorspheres with and without MYC/MYCN amplification. The in vivo efficacy of glycolyic inhibition was tested using NAMPT inhibitors in MYCN-amplified patient-derived glioblastoma orthotopic xenograft mouse models.Enforced Myc overexpression increased glucose flux and expression of glycolytic enzymes in glioblastoma cells. Myc and N-Myc knockdown and Myc overexpression systems demonstrated that Myc activity determined sensitivity and resistance to inhibition of glycolysis. Small-molecule inhibitors of glycolysis, particularly NAMPT inhibitors, were selectively toxic to MYC/MYCN-amplified patient-derived glioblastoma tumorspheres. NAMPT inhibitors were potently cytotoxic, inducing apoptosis and significantly extended the survival of mice bearing MYCN-amplified patient-derived glioblastoma orthotopic xenografts.Myc activation in glioblastoma generates a dependency on glycolysis and an addiction to metabolites required for glycolysis. Glycolytic inhibition via NAMPT inhibition represents a novel metabolically targeted therapeutic strategy for MYC or MYCN-amplified glioblastoma and potentially other cancers genetically driven by Myc. Clin Cancer Res; 22(17); 4452-65. ©2016 AACR.
Case 45-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Robert W. Finberg, Anthony R. Mattia
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 47-year-old man with relapsed acute myelogenous leukemia was admitted to the hospital for an allogeneic bone marrow transplantation.The patient had been well until 13 months earlier, when lymphadenopathy developed abruptly and he received a diagnosis of acute myelogenous leukemia, subtype M2 according to the French-American-British classification. He underwent induction chemotherapy with idarubicin and cytarabine. Because of persistent evidence of leukemia in a bone marrow specimen obtained on day 14 he received a second course of the same agents. Complications of chemotherapy included a dental abscess, streptococcal bacteremia, an intestinal helminthic infestation, and oral mucositis due . . .