tbuckley/cabot-search huggingface dataset:
Congenital amegakaryocytic thrombocytopenia iPS cells exhibit defective MPL-mediated signaling
Authors: Shinji Hirata, Naoya Takayama, Ryoko Jono-Ohnishi, Hiroshi Endo, Sou Nakamura, Takeaki Dohda, Masanori Nishi, Yuhei Hamazaki, Ei-ichi Ishii, Shin Kaneko, Makoto Otsu, Hiromitsu Nakauchi, Shinji Kunishima, Koji Eto
Journal: Journal of Clinical Investigation (2013)

Congenital amegakaryocytic thrombocytopenia (CAMT) is caused by the loss of thrombopoietin receptor–mediated (MPL-mediated) signaling, which causes severe pancytopenia leading to bone marrow failure with onset of thrombocytopenia and anemia prior to leukopenia. Because Mpl–/– mice do not exhibit the human disease phenotype, we used an in vitro disease tracing system with induced pluripotent stem cells (iPSCs) derived from a CAMT patient (CAMT iPSCs) and normal iPSCs to investigate the role of MPL signaling in hematopoiesis. We found that MPL signaling is essential for maintenance of the CD34+ multipotent hematopoietic progenitor (MPP) population and development of the CD41+GPA+ megakaryocyte-erythrocyte progenitor (MEP) population, and its role in the fate decision leading differentiation toward megakaryopoiesis or erythropoiesis differs considerably between normal and CAMT cells. Surprisingly, complimentary transduction of MPL into normal or CAMT iPSCs using a retroviral vector showed that MPL overexpression promoted erythropoiesis in normal CD34+ hematopoietic progenitor cells (HPCs), but impaired erythropoiesis and increased aberrant megakaryocyte production in CAMT iPSC–derived CD34+ HPCs, reflecting a difference in the expression of the transcription factor FLI1. These results demonstrate that impaired transcriptional regulation of the MPL signaling that normally governs megakaryopoiesis and erythropoiesis underlies CAMT.
Platelet transfusion therapy in acute leukemia: Lack of effect of splenomegaly on transfusion requirements and risk of hemorrhage
Authors: Thomas E. Witzig, Barbara S. Ducatman, Mark R. Wick, Louis Letendre, S. Breanndan Moore, Duane M. Ilstrup, Howard F. Taswell
Journal: American Journal of Hematology (1985)

Platelet transfusions are an important supportive measure during treatment for acute nonlymphocytic leukemia (ANLL). The presence of splenomegaly may produce decreased posttransfusion platelet increments leading some to recommend an increased dose of platelets per transfusion in this situation. Forty-nine newly diagnosed patients with ANLL were evaluated during 1980 and 1981, and 24% had palpable splenomegaly. Although treated with usual doses of platelets per transfusion, there was no detectable statistical increase in transfusion requirement or incidence of hemorrhage in patients with splenomegaly. Experimental evidence indicates that the splenic platelet pool enlarges with splenomegaly, but the life span of circulating platelets is not significantly changed. Furthermore, the splenic platelet pool is in dynamic equilibrium with the circulating platelet pool thus allowing these platelets to participate in hemostasis. Although posttransfusion increment in platelet count may be less, it appears that platelet transfusion therapy need not be altered solely because of splenomegaly.
Human resources for health: overcoming the crisis
Authors: Lincoln Chen, Timothy Evans, Sudhir Anand, Jo Ivey Boufford, Hilary Brown, Mushtaque Chowdhury, Marcos Cueto, Lola Dare, Gilles Dussault, Gijs Elzinga, Elizabeth Fee, Demissie Habte, Piya Hanvoravongchai, Marian Jacobs, Christoph Kurowski, Sarah Michael, Ariel Pablos-Mendez, Nelson Sewankambo, Giorgio Solimano, Barbara Stilwell, Alex de Waal, Suwit Wibulpolprasert
Journal: The Lancet (2004)
Donor B-cell alloantibody deposition and germinal center formation are required for the development of murine chronic GVHD and bronchiolitis obliterans
Authors: Mathangi Srinivasan, Ryan Flynn, Andrew Price, Ann Ranger, Jeffrey L. Browning, Patricia A. Taylor, Jerome Ritz, Joseph H. Antin, William J. Murphy, Leo Luznik, Mark J. Shlomchik, Angela Panoskaltsis-Mortari, Bruce R. Blazar
Journal: Blood (2011)
Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin
Authors: Maritza A. Middelkamp-Hup, Madhu A. Pathak, Concepcion Parrado, David Goukassian, Francisca Rius-Díaz, Martín C. Mihm, Thomas B. Fitzpatrick, Salvador González
Journal: Journal of the American Academy of Dermatology (2004)
Anaphylactic reaction caused by neoallergens in heated pecan nut
Authors: K. Malanin, M. Lundberg, S. G. O. Johansson
Journal: Allergy (1995)

An atopic girl experienced an anaphylactic reaction after eating cookies containing pecan nuts. Investigations revealed that she had developed IgE antibodies exclusively specific against allergenic determinants present in aged or heated pecan nuts, but not in fresh pecans. These neoallergenic determinants were located on protein(s) with a molecular weight of approximately 15 kDa. Neoallergens appearing during heating or storing of foods may be important in some anaphylactic reactions.
Lysophosphatidylserine (Lyso-PS) Made in Activated Neutrophils Enhances Their Clearance “Alive or Dead” by Macrophage Via Activation of a G2A to PKA to Rac Signaling Cascade: Implications for Restoring Normal Resolution of Neutrophilia in Chronic Granulomatous Disease (CGD)
Authors: D. Bratton, R. Fernandez-Boyanapalli, P. Henson, S.C. Frasch
Journal: Journal of Allergy and Clinical Immunology (2010)
Long-Term Outcome of Anti–Glomerular Basement Membrane Antibody Disease Treated with Plasma Exchange and Immunosuppression
Authors: Jeremy B. Levy, A. Neil Turner, Andrew J. Rees, Charles D. Pusey
Journal: Annals of Internal Medicine (2001)

Anti-glomerular basement membrane (GBM) antibody disease is an autoantibody-mediated disorder that usually presents as rapidly progressive glomerulonephritis, often with pulmonary hemorrhage (the Goodpasture syndrome). It is reported that patients with severe renal failure do not generally recover renal function.To examine the long-term outcome of severe anti-GBM antibody disease.Retrospective review of patients treated for confirmed anti-GBM antibody disease over 25 years.A tertiary referral center in the United Kingdom.71 treated patients with anti-GBM antibody disease.All patients received plasma exchange, prednisolone, and cyclophosphamide.Patient and renal survival, renal histology, and antibody levels.Patients who presented with a creatinine concentration less than 500 micromol/L (5.7 mg/dL) (n = 19) had 100% patient survival and 95% renal survival at 1 year and 84% patient survival and 74% renal survival at last follow-up. In patients who presented with a creatinine concentration of 500 micromol/L or more (>/=5.7 mg/dL) (n = 13) but did not require immediate dialysis, patient and renal survival were 83% and 82% at 1 year and 62% and 69% at last follow-up. In patients who presented with dialysis-dependent renal failure (n = 39), patient and renal survival were 65% and 8% at 1 year and 36% and 5% at last follow-up. All patients who required immediate dialysis and had 100% crescents on renal biopsy remained dialysis dependent.Patients with the Goodpasture syndrome and severe renal failure should be considered for urgent immunosuppression therapy, including plasma exchange, to maximize the chance of renal recovery. Patients needing immediate dialysis are less likely to recover.
LOCAL ANESTHESIA IN MAJOR AND MINOR OPERATIONS ON THE EARAS OBSERVED IN PROFESSOR PULITZER'S CLINIC IN VIENNA.
Authors: GEORGE PAULL MARQUIS
Journal: JAMA (1905)

During our term of service as clinical assistants in Professor Pulitzer's clinic we had the opportunity to observe and to study the various methods of applying local anesthesia in otology. Although the Schleich and other solutions from time to time had been used with various degrees of success, it remained for Neumann, assistant to Professor Pulitzer, successfully to develop a method of local anesthesia, by means of which almost any operation can be performed on the ear without more than passing inconvenience to the patient. Neumann first tried this method in the case of a strong Hungarian—a coal miner by trade—who had suffered for years with a chronic otitis media. In this case he injected 7 c.c. of a 1 per cent. solution of cocain with five drops of tonogen<sup>1</sup>to each c.c. of the solution, and the
CMV-specific CD8+ T-cell function is not impaired in chronic lymphocytic leukemia
Authors: G. Doreen te Raa, Maria Fernanda Pascutti, Juan J. García-Vallejo, Emilie Reinen, Ester B. M. Remmerswaal, Ineke J. M. ten Berge, René A. W. van Lier, Eric Eldering, Marinus H. J. van Oers, Sanne H. Tonino, Arnon P. Kater
Journal: Blood (2013)
F-18 Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis of Inflammatory Bowel Disease
Authors: EWALD KRESNIK, PETER MIKOSCH, HANS JÜRGEN GALLOWITSCH, MARTIN HEINISCH, PETER LIND
Journal: Clinical Nuclear Medicine (2001)

KRESNIK, EWALD M.D.; MIKOSCH, PETER M.D.; GALLOWITSCH, HANS JÜRGEN M.D.; HEINISCH, MARTIN; LIND, PETER M.D. Author Information
Adrenocorticotrophic Hormone in Acute Disseminated Lupus Erythematosus
Authors: D. G. Ferriman, R. B. N. Wilsdon
Journal: BMJ (1950)

surgery was considered inadvisable.A week after incision of the thighs spontaneous abortion occurred, three days later thrombophlebitis was observed in both antecubital veins at the site of vein punctures, and three days after that left foot-drop occurred.The white cell count was then 38,400 per c.mm. (92% polymorphs).After a further 12 days the skin sloughed in both legs over a circular area of 5 in.(12.5 cm.) diameter in the left leg and 2 in.(5 cm.) diameter in the right; the patient was apyrexial and free from pain.Separation of the sloughs and slow epithelization occurred, the foot-drop recovered, and the white cell count fell to 8,100 per c.mm. Procaine and penicillin intradermal sensitivity tests were negative.
Cytokine-Based Therapy and Biochemotherapy for Advanced Melanoma
Authors: Michael B. Atkins
Journal: Clinical Cancer Research (2006)

Abstract A variety of immunotherapeutic approaches have shown activity in patients with metastatic melanoma with the best results being observed with interleukin 2 (IL-2). Follow-up data through 2004 confirm the durability of responses produced by the Food and Drug Administration–approved high-dose IL-2 regimen in this patient population. Efforts to develop more tolerable and/or effective IL-2–based treatment regimens by either prolonged administration of lower doses or the combination of IL-2 with other cytokines, monoclonal antibodies, or vaccines have yet to produce results superior to those seen with high-dose IL-2 alone. Recent investigations have suggested that, in some patients, IL-2 may expand regulatory T-cell populations leading to immune tolerance rather than antitumor immunity. Efforts to shift this balance in favor of immune rejection by reducing the confounding effects of regulatory T cells on IL-2 therapy or the use of novel and potentially more purely immunostimulatory cytokines are ongoing. Despite promising phase 2 data, phase 3 studies have failed to show meaningful clinical benefit for the combination of cytokines with cytotoxic chemotherapy, so-called “biochemotherapy.” Nonetheless, recent investigations with biochemotherapy followed by maintenance immunotherapy suggest that biochemotherapy may still have a role as a “bridge to immunotherapy” in some patients with rapidly progressive disease. Given the low number of patients achieving durable benefit with cytokine-based immunotherapy, considerable recent effort has focused on identifying predictors of therapeutic response. Investigations suggest that immune responsiveness may be predetermined by a tumor microenvironment conducive to immune recognition and the host propensity to develop autoimmunity. Efforts to understand and further define pretreatment predictors of response through the use of gene expression and proteomic techniques are ongoing and raise the potential for eventually limiting cytokine-based immunotherapy to those most likely to benefit.
CORONARY ARTERY BYPASS GRAFTING WITH CONCOMITANT CARDIAC RESYNCHRONIZATION THERAPY IN PATIENTS WITH ISCHEMIC HEART FAILURE AND LEFT VENTRICULAR DYSSYNCHRONY: RESULTS FROM A MULTICENTER STUDY
Authors: Aleksandr Borisovich Romanov, Evgeny Pokushalov, Aleksander Cherniavskiy, Aleksander Karaskov, Kinga Goscinska-Bis, Jaroslaw Bis, Andrzej Bochenek
Journal: Journal of the American College of Cardiology (2011)
Activated immunocompetent cells in human skin lymph derived from irritant contact dermatitis: an immunomorphological study
Authors: CH.U. BRAND, TH. HUNZIKER, TH. SCHAFFNER, A. LIMAT, H.A GERBER, L.R BRAATHEN
Journal: British Journal of Dermatology (1995)

By means of microsurgical lymph cannulation, skin lymph was sampled in the course of a sodium lauryl sulphate (SLS)-induced irritant contact dermatitis in human volunteers. The lymph cells were isolated by centrifugation, and then characterized immunocytochemically using different monoclonal antibodies, and in the late phase of the skin reaction also by electron microscopy. Analyses of lymph cells before the induction of the contact dermatitis revealed median values of about 60% T cells (CD4/CD8 ratio about 2:1), 4% Langerhans cells (LCs), and 1% B cells. The remainder were varying proportions of erythrocytes and uncharacterized cells. During the skin reaction, and even after resolution of the clinical signs of dermatitis, a relative and absolute increase of T and B cells, as well as of HLA-DR positive cells, paralleled the previously reported increase of LCs; a high percentage of the T cells were CD4 and CD8 negative. In addition, surface markers such as CD11a, CD25, CD54 and CD58 were detected on lymph cells sampled during the irritant skin reaction. Cell rosettes observed in the lymph throughout the experiment were analysed in the late phase of the skin reaction, and showed a central LC with three to five peripheral, in part activated, T cells, ultrastructurally revealing gap junction-like structures between the two cell types. These data indicate that immunocompetent cells in the skin are activated by a variety of non-immunological stimuli such as operative trauma and irritant contact dermatitis.
Chance, Continuity, and Change in Hospital Mortality Rates
Authors: Harold S. Luft
Journal: JAMA (1993)

To assess whether risk-adjusted mortality rates for hospitals reflect primarily chance variation.Observation over time.All 115 California hospitals with five or more coronary artery bypass graft (CABG) patients in any year 1983 to 1989.All CABG patients aged 18 years and older excluding those with other open heart procedures and percutaneous transluminal coronary angioplasty on the day of CABG surgery (n = 132,750).Inpatient mortality adjusted for age, gender, chronic comorbidities, timing of surgery, and presence of additional procedures.Data were derived from routinely collected hospital discharge abstracts. Observed and expected semiannual mortality rates were examined for each hospital to identify consistent patterns over time. Using the quartile of patients with the highest predicted risk (average mortality, 10%), high- and low-outlier hospitals were identified from 2 consecutive years of pooled data and outcomes 2 years later were examined. Each hospital-year observation was also examined individually to identify outliers and to assess differences for observed and expected death rates, patient volume, and other characteristics.Some hospitals showed consistently lower-than-expected inpatient mortality. Some hospitals had periods of significantly higher-than-expected mortality followed by a correction. High-outlier hospitals that were selected based on 2 years of data had mortality rates 2 years later that averaged 31% above expected, while low-outlier hospitals had rates 2 years later that averaged 28% below expected. On a contemporaneous basis, high outliers had proportionately more transfers to other acute care hospitals and longer postoperative stays among survivors.Risk-adjusted outcomes for CABG patients derived from administrative data exhibit substantial patterns of consistency. Such patterns cannot be detected for low-risk patients but are evident for the top quartile of patients stratified by risk. Even with reporting lags and changes in hospital outcomes over time, a policy of channeling high-risk patients away from high-outlier hospitals and toward low-outlier hospitals could lower their overall risk-adjusted mortality rate by 45% [corrected].
The incidence of gastroschisis: Is also increasing in Spain, particularly among babies of young mothers
Authors: Eva Bermejo, Jacobo Mendioroz, Lourdes Cuevas, María-Luisa Martínez-Frías
Journal: BMJ (2006)

<h3>Background</h3> We preliminarily found a SNP (rs6871626, A vs. C) in <i>IL-12B</i> region as a susceptibility gene to Takayasu arteritis (TAK) by genome-wide association study. <i>IL-12B</i> encodes IL-12p40 that is a component of both IL-12p70 and IL-23. The significance of IL-12p40 in pathophysiology of TAK has not been fully investigated yet. Moreover, there has been no consistent evidence about whether IL-12p70 or IL-23 is important in TAK. <h3>Objectives</h3> 1) To investigate the expression of IL-12p40 in patients with TAK, 2) reveal which is more important to pathophysiology of TAK, IL-12p70 or IL-23, and 3) examine the influence of SNP to the cytokine production. <h3>Methods</h3> We collected sera from 43 TAK patients and 19 healthy controls (HCs), and measured IL-12p40, IL-12p70 and IL-23 with ELISA. Next, we collected whole blood from 18 TAK patients and 12 HCs, and isolated monocytes with RosetteSep™. The monocytes were incubated with IL-6, IL-10 and GM-CSF, and then stimulated with INF-γ and LPS. Then we measured the cytokines in culture supernatant with ELISA. <h3>Results</h3> IL-12p40 and IL-12p70 in sera of TAK patients were significantly higher than those of HCs (p=0.031 and p&lt;0.001, respectively), whereas there were no differences in serum of IL-23 levels between TAK patients and HCs. IL-12p40 and IL-12p70 in sera of TAK patients whose allele at rs6871626 is AA or AC (defined as risk patients) were significantly higher than those of HCs (p=0.018 and p&lt;0.001, respectively), whereas there were no differences in serum IL-23 levels among risk patients, TAK patients with CC allele (defined as non-risk patients) and HCs. Supernatant IL-12p40 and IL-12p70 levels from monocytes of risk patients were significantly higher than those of non-risk patients (p=0.044 and p=0.032, respectively) or those of HCs (p=0.032 and p=0.0015, respectively). Supernatant IL-23 from monocytes of risk patients were significantly higher than those of non-risk patients (p=0.04). <h3>Conclusions</h3> IL-12p40 and IL-12p70 but not IL-23 may play an important role in pathophysiology of TAK, and the risk allele of rs6871626 could contribute to production of these cytokines. <h3>Disclosure of Interest</h3> None declared
Apparent reduction of endogenous creatinine clearance by salicylate treatment.
Authors: H C Burry, P A Dieppe
Journal: BMJ (1976)

A prospective study of nine patients with rheumatoid arthritis and 11 healthy volunteers who started salicylate treatment showed that in 18 of the 20 subjects creatinine clearance values fell the average being 25%. Serum creatinine concentration was increased by an average of 38%, although blood urea levels were unchanged. Since 51Cr-edetic acid clearance tests performed at the same time in 12 of the subjects were not affected, the fall in creatinine clearance was probably not due to impaired glomerular function, and salicylate ingestion may therefore invalidate the creatinine clearance test as an index of glomerular filtration rate. It is clearly important to inquire into the patient9s analgesic comsumption when using the creatinine clearance test to assess glomerular function.
Abstract 5502: Therapeutic efficacy prediction by quantitative protein analysis in response to anti-cancer agents
Authors: Satoshi S. Nishizuka, Kazushige Ishida, Teppei Matsuo, Hironobu Noda, Takeshi Iwaya, Go Wakabayashi
Journal: Cancer Research (2010)

Abstract Background: The conventional chemosensitivity test employs a growth suppression assay. However, surgically removed specimens often have low viability which makes the assay unreliable, since the poor cell growth may be associated with the low viability instead of the chemosensitivity of the cell. On the other hand, we do know that the level of proteins involved in signal transduction is changed prior to cellular responses to the anti-cancer agents. In the present study, we investigated if protein signaling within a 24-hour exposure of the anti-cancer agents can predict the cellular fate at 72-hour time points. Materials and Methods: The human colon cancer cell line, HCT116, was exposed to three different DNA-damaging anti-cancer agents including gamma irradiation, ultraviolet, and doxorubicin. The anti-cancer agent-exposed cell pellets from different conditions (e.g., doses, and time-points) were collected to produce a lysate array, which finally accommodated more than 500 samples on a single glass slide. Array image and quantitative protein analyses were performed with the P-SCAN and ProteinScan programs. Results: A total of 19 protein species were tested on a lysate array, providing kinetic information of the protein. In response to all three agents, p53 protein was stabilized and the level increased over time in a dose-dependent manner. Upon detailed time-course analysis, however, an oscillation was seen in response to gamma irradiation, indicating the presence of a feedback loop. Comparing the rate of increasing levels of p21 and CyclinD3 within 24 hours in response to doxorubicin administration, the rates are well associated with the status of cell fate. In other words, when the rate of p21 is higher than CyclinD3, it is associated with a G2 arrest at 72 hours, whereas a higher CyclinD3 rate is associated with apoptosis at 72 hours after drug administration. Conclusion: Some events occurring at 72 hours can be predicted by seeing the quantitative level of protein kinetics within 24 hours. Most of the primary culture cells can survive for only a short period of time. The protein kinetics may be a useful clinical chemosensitivity predictor even when using low viability specimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5502.
Abstract 2027: Carbamylated albumin increase MMP9 activity via ERK MAPK pathway
Authors: Jin Young Kim, Keon Uk Park, So Jin Shin, Il Seon Hwang, Eunyoung Ha, Hun-Mo Ryoo
Journal: Cancer Research (2012)

Abstract Objective: Carbamylation, the binding of cyanate to amino acid lysine residues, is a post-translational modification. Pathophysiological consequences of carbamylation and adverse effects of carbamylated proteins remain poorly understood. This study was designed to influence of carbamylated albumin on matrix metalloproteinase(MMP) expressions in rat mesangial cells (RMC). Methods and Results: The effect of carbamylated albumin was evaluated using zymography, Western blot analysis, MMP-9 promoter luciferase assay, and ELISA. We found that carbamylated albumin significantly increased MMP-9 productions in RMCs via stimulating MMP-9 promoter activity and ERK1/2 MAPK phosphorylation. DecreasedTIMP-1 activity by carbamylated albumin was not observed. Conclusion: We demonstrated that carbamylated albumin increased MMP-9 activity via ERK1/2MAPK mediated pathway and further studies as to the functions of carbamylated albumin will be of merit. 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 2027. doi:1538-7445.AM2012-2027