tbuckley/cabot-search huggingface dataset:
Bone marrow scintigraphy using Technetium-99m antigranulocyte antibody in malignant lymphomas
Authors: T Krause, N Eisenmann, M Reinhardt, J Bathmann, C Altehoefer, J Finke, E Moser
Journal: Annals of Oncology (1999)

The purpose of this study was to elucidate the clinical reliability of immunoscintigraphy (IS) to detect infiltration of the bone marrow in patients with malignant lymphoma.Whole body IS was performed in 103 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) using Tc-99m labelled anti-NCA-95 which allows visualization of the granulopoietic bone marrow. Of these, 52% were studied prior to any therapy. Findings were compared to posterior iliac crest biopsy as well as MRI and/or follow-up examination. Criteria of marrow infiltration were a positive biopsy, positive follow-up, or positive results of MRI.Comparison of IS and biospy revealed concordant findings in 69 and discordant findings in 34 of 103 patients. Of the 34 patients with discordant results, IS showed lesions suspicious of bone marrow infiltration in 29 patients despite normal biopsy findings. When follow-up and additional examinations were taken into consideration, 10 patients remained with probably false positive and five with false negative IS findings. IS proved to be highly sensitive and specific in patients with HD (100% and 84%, respectively) and high-grade NHL (93% and 84%, respectively). Moderate sensitivity (60%) was found in low-grade NHL. This was possibly due to false negative IS in three to five patients with chemotherapy in contrast to one of five false negative results in patients without chemotherapy.Bone marrow scintigraphy using antigranulocyte antibodies is highly sensitive in HD and high-grade NHL. Positive findings in IS subsequent to a negative biopsy should be followed by guided re-biopsy or MRI.
Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b–2 dose-escalation study
Authors: Paul G Richardson, Sundar Jagannath, Philippe Moreau, Andrzej J Jakubowiak, Marc S Raab, Thierry Facon, Ravi Vij, Darrell White, Donna E Reece, Lotfi Benboubker, Jeffrey Zonder, L Claire Tsao, Kenneth C Anderson, Eric Bleickardt, Anil K Singhal, Sagar Lonial
Journal: The Lancet Haematology (2015)
Disease evolution and outcomes in familial AML with germline CEBPA mutations
Authors: Kiran Tawana, Jun Wang, Aline Renneville, Csaba Bödör, Robert Hills, Chey Loveday, Aleksandar Savic, Frederik W. Van Delft, Jennifer Treleaven, Panayiotis Georgiades, Elizabeth Uglow, Norio Asou, Naokuni Uike, Maruša Debeljak, Janez Jazbec, Philip Ancliff, Rosemary Gale, Xavier Thomas, Valerie Mialou, Konstanze Döhner, Lars Bullinger, Beatrice Mueller, Thomas Pabst, Matthias Stelljes, Brigitte Schlegelberger, Eva Wozniak, Sameena Iqbal, Jessica Okosun, Shamzah Araf, Anne-Katrine Frank, Felicia B. Lauridsen, Bo Porse, Claus Nerlov, Carolyn Owen, Inderjeet Dokal, John Gribben, Matthew Smith, Claude Preudhomme, Claude Chelala, Jamie Cavenagh, Jude Fitzgibbon
Journal: Blood (2015)
Increased thromboxane mediates the adverse renal effects of interleukin-2 in rats.
Authors: D Rubinger, E Cohen, Y Haviv, J Bernheim, E Shiloni, M M Popovtzer
Journal: Journal of the American Society of Nephrology (1994)

The capillary leak syndrome with decreased GFR and renal water and sodium retention after recombinant interleukin-2 (IL-2) administration may arise from endothelial activation via an increase in prostaglandin synthesis. This study was undertaken to better define the role of the prostaglandin system in the renal and metabolic effects of IL-2 administration in rats. The chronic administration of IL-2 (100,000 U/kg, thrice daily, ip) resulted in a significant increase in body weight, a decrease in GFR and in the urinary excretion of sodium and potassium, and an increase in the urinary excretion of thromboxane (TXB2). After combined IL-2 and low-dose indomethacin (1.7 mg/kg per day po), a significant decrease in body weight with normalization of GFR, of the urinary excretion of Na, and of urinary TXB2 was noted in animals receiving combined therapy as compared with those receiving IL-2 alone. In contrast, high-dose indomethacin administration (33.3 mg/kg po for the last 3 days of the study) was associated with a further decrease in GFR, enhancement of the sodium and potassium retention, and suppression of prostaglandin E2 excretion. The administration of the thromboxane receptor antagonist SQ 29548 in IL-2-treated rats led to a reversal of the fall in GFR induced by the lymphokine without significant changes in urinary sodium excretion. These results support the hypothesis that thromboxane is an important mediator of the renal and systemic effects of IL-2. These effects are reversed at least partly by low-dose indomethacin, which selectively suppresses thromboxane A2 (TXA2) synthesis, or by TXA2 receptor antagonism.
Activation of basophil and mast cell histamine release by eosinophil granule major basic protein.
Authors: M C O'Donnell, S J Ackerman, G J Gleich, L L Thomas
Journal: The Journal of Experimental Medicine (1983)

Major basic protein (MBP) is a primary constituent of eosinophil granules. In this report, we demonstrate that MBP from human eosinophil granules initiates a nonlytic histamine release from human leukocytes. A direct effect of MBP on basophils was confirmed using purified human basophils. The kinetics of release were similar to those reported for poly-L-arginine, although MBP was less potent than poly-L-arginine of similar molecular weight. Reduction and alkylation of MBP diminished both the potency and efficacy of the molecule. Native MBP also stimulated histamine secretion from purified rat peritoneal mast cells in a manner characteristic of other polycations. These results emphasize the bidirectional nature of the basophil/mast cell-eosinophil regulatory axis.
SLAMF1 regulation of chemotaxis and autophagy determines CLL patient response
Authors: Cinzia Bologna, Roberta Buonincontri, Sara Serra, Tiziana Vaisitti, Valentina Audrito, Davide Brusa, Andrea Pagnani, Marta Coscia, Giovanni D’Arena, Elisabetta Mereu, Roberto Piva, Richard R. Furman, Davide Rossi, Gianluca Gaidano, Cox Terhorst, Silvia Deaglio
Journal: Journal of Clinical Investigation (2015)

Chronic lymphocytic leukemia (CLL) is a variable disease; therefore, markers to identify aggressive forms are essential for patient management. Here, we have shown that expression of the costimulatory molecule and microbial sensor SLAMF1 (also known as CD150) is lost in a subset of patients with an aggressive CLL that associates with a shorter time to first treatment and reduced overall survival. SLAMF1 silencing in CLL-like Mec-1 cells, which constitutively express SLAMF1, modulated pathways related to cell migration, cytoskeletal organization, and intracellular vesicle formation and recirculation. SLAMF1 deficiency associated with increased expression of CXCR4, CD38, and CD44, thereby positively affecting chemotactic responses to CXCL12. SLAMF1 ligation with an agonistic monoclonal antibody increased ROS accumulation and induced phosphorylation of p38, JNK1/2, and BCL2, thereby promoting the autophagic flux. Beclin1 dissociated from BCL2 in response to SLAMF1 ligation, resulting in formation of the autophagy macrocomplex, which contains SLAMF1, beclin1, and the enzyme VPS34. Accordingly, SLAMF1-silenced cells or SLAMF1(lo) primary CLL cells were resistant to autophagy-activating therapeutic agents, such as fludarabine and the BCL2 homology domain 3 mimetic ABT-737. Together, these results indicate that loss of SLAMF1 expression in CLL modulates genetic pathways that regulate chemotaxis and autophagy and that potentially affect drug responses, and suggest that these effects underlie unfavorable clinical outcome experienced by SLAMF1(lo) patients.
Human rights in the new Global Strategy
Authors: Jyoti Sanghera, Lynn Gentile, Imma Guerras-Delgado, Lucinda O’Hanlon, Alfonso Barragues, Rachel Louise Hinton, Rajat Khosla, Kumanan Rasanathan, Marcus Stahlhofer
Journal: BMJ (2015)

By recognising the centrality of human rights, the revised Global Strategy encourages some bold shifts in improving the health and wellbeing of women, children, and adolescents, say <b>Jyoti Sanghera and colleagues</b>
Autologous HER2 CMV bispecific CAR T cells are safe and demonstrate clinical benefit for glioblastoma in a Phase I trial.
Authors: Nabil Ahmed, Vita Brawley, Meenakshi Hegde, Kevin Bielamowicz, Amanda Wakefield, Alexia Ghazi, Aidin Ashoori, Oumar Diouf, Claudia Gerken, Daniel Landi, Mamta Kalra, Zhongzhen Yi, Cliona Rooney, Gianpietro Dotti, Adrian Gee, Helen Heslop, Stephen Gottschalk, Suzanne Powell, Robert Grossman, Winfried Wels, Yzonne Kew, David Baskin, Jonathan Zhang, Pamela New, John Hicks
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Glioblastoma (GBM) remains incurable with current standard-of-care therapies. Adoptive T cell transfer holds the promise to improve outcomes for GBM patients. We report on the results of the Phase I clinical study, [NCT01109095][1], administering autologous CMV.pp65 T cells
B16F0 melanoma exosomes deliver a unique and complex biological payload that includes Ptpn11 to suppress T lymphocyte function
Authors: Yueting Wu, Wentao Deng, Emily McGinley, David J Klinke
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Host immunity is coordinated through a complex network of intercellular communication. Similar to the sculpting of tumor antigens during oncogenesis, a related hypothesis is that proteins secreted by malignant cells are shaped by somatic evolution. Malignant cells that then emerge
Rise in Albuminuria and Blood Pressure in Patients Who Progressed to Diabetic Nephropathy in the Diabetes Control and Complications Trial
Authors: WILLIAM THOMAS, YINGJIA SHEN, MARK E. MOLITCH, MICHAEL W. STEFFES
Journal: Journal of the American Society of Nephrology (2001)

Abstract. The Diabetes Control and Complications Trial (DCCT) enrolled 1441 participants to address the role of intensive therapy for type 1 diabetes mellitus on the onset and progression of microvascular complications. To examine the timing of elevated systolic BP (SBP) and diastolic BP (DBP) and increased albumin excretion rate (AER) in the progression to clinical diabetic nephropathy (AER &gt; 300 mg/24 h on two consecutive visits from a baseline of &lt;100 mg/24 h) and, importantly, to control for initial values of hemoglobin A 1c , a retrospective case-control study was assembled from the records of the publicly released DCCT data. Participants who progressed to clinical diabetic nephropathy—progressors—were matched with participants of the same gender and treatment group who had similar baseline values for DBP, SBP, AER AER and hemoglobin A 1c , but who did not progress to clinical diabetic nephropathy—matched controls. In the conventional treatment group, the 21 progressors exhibited a significant rise in mean AER (above their own baseline levels and above values in the matched controls) at year 2 of the DCCT. In contrast, the progressors' mean DBP and SBP were not significantly higher than baseline until year 3 (DBP) or year 4 (SBP) and not significantly higher than the matched controls until year 4 (both DBP and SBP). On the individual level, 19 of 21 (90%) progressors reached clinical diabetic nephropathy before the diagnosis of hypertension (140/90 mmHg). In the intensive treatment group, however, the rise in DBP preceded the rise in AER by 1 to 2 yr among the six progressors. Both intensively treated progressors who experienced hypertension reached this before AER &gt; 300 mg/24 h. These results underline the early and prognostic rise in AER in diabetic patients, but only in those who received conventional treatment. The evolution of diabetic renal disease may follow a different course in patients who receive intensive diabetic treatment.
Intensity of Continuous Renal-Replacement Therapy
Authors: Marlies Ostermann, Rene W Chang
Journal: New England Journal of Medicine (2010)

To the Editor: In the Randomized Evaluation of Normal versus Augmented Level (RENAL) Replacement Therapy Study (Oct. 22 issue),1 investigators compared low-intensity versus high-intensity renal-replacement therapy. One of the secondary outcomes was the development of new organ failure. However, the criteria for “nonrenal organ failure” were not provided. Second, in subgroup analyses, the RENAL study showed that there was no mortality benefit with high-intensity treatment in patients with sepsis, cardiovascular dysfunction, or failure of at least one nonrenal organ. In a study involving 1847 critically ill patients receiving renal-replacement therapy, we recently reported that the number of failed organ systems at the time of such therapy had a significant effect on the rate of death in the intensive care unit, ranging from 38% in patients with one organ failure to 85.6% in patients with more than three failed organ systems.2 The RENAL study was not designed to perform subgroup analyses in patients with three or more associated failed organ systems. The question remains whether renal-replacement therapy should be individualized in patients with acute kidney injury and multiorgan failure and whether there is a role for high-intensity renal-replacement therapy in this group.
Adalimumab Induction Therapy for Crohn Disease Previously Treated with Infliximab
Authors: William J. Sandborn, Paul Rutgeerts, Robert Enns, Stephen B. Hanauer, Remo Panaccione, Ju Li, Marie R. Rosenfeld, Jeffrey D. Kent, Paul F. Pollack
Journal: Annals of Internal Medicine (2015)

Background: Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent. Objective: To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events. Design: 4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005). Setting: 52 sites in the United States, Canada, and Europe. Patients: 325 adults 18 to 75 years of age who had a history of Crohn disease for 4 months or more that was moderate to severe at baseline (Crohn’s Disease Activity Index [CDAI] score, 220 to 450 points). Intervention: Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points. Measurements: The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured. Results: A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No patients in the adalimumab group and 4 of 166 patients in the placebo group had a serious infection. Limitations: The trial did not directly compare alternative active treatments and did not evaluate maintenance of response or longterm immunogenicity of adalimumab. Conclusion: Adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy.
The presence or severity of pulmonary hypertension does not affect outcomes for single-lung transplantation
Authors: Walker A Julliard, Keith C Meyer, Nilto C De Oliveira, Satoru Osaki, Richard C Cornwell, David A Sonetti, James D Maloney
Journal: Thorax (2015)

Advanced lung disease (ALD) that requires lung transplantation (LTX) is frequently associated with pulmonary hypertension (PH). Whether the presence of PH significantly affects the outcomes following single-lung transplantation (SLT) remains controversial. Therefore, we retrospectively examined the outcomes of 279 consecutive SLT recipients transplanted at our centre, and the patients were split into four groups based on their mean pulmonary artery pressure values. Outcomes, including long-term survival and primary graft dysfunction, did not differ significantly for patients with versus without PH, even when PH was severe. We suggest that SLT can be performed safely in patients with ALD-associated PH.
Comparing Patient-Derived Xenograft and Computational Response Prediction for Targeted Therapy in Patients of Early-Stage Large Cell Lung Cancer
Authors: Jian Li, Changkun Ye, Ulrich R. Mansmann
Journal: Clinical Cancer Research (2015)

Targeted therapy (TT) provides highly effective cancer treatment for appropriately selected individuals. A major challenge of TT is to select patients who would benefit most.The study uses cancer material from 25 patients primarily diagnosed with non-small cell lung cancer (NSCLC). Patient-derived xenografts (PDXs) are treated with cetuximab and erlotinib. Treatment response is measured by tumor shrinkage comparing tumor volume at day 25 (V25) with tumor volume at baseline (V0). Shrinkage below 40% is considered as treatment response: V25/V0 < 0.4 (<40%). Furthermore, RNA-seq data from each tumor sample are used to predict tumor response to either treatment using an in silico molecular signaling map (MSM) approach.PDX response was 40% (10/25; 95% CI [21.13%, 61.34%]) under cetuximab and 20% (5/25; 95% CI [6.83%, 40.70%]) under erlotinib. MSM predicted response was 48% (12/25; 95% CI [27.8%, 68.7%]) under cetuximab and 40% (10/25; 95% CI [21.13%, 61.34%]) under erlotinib. Agreement between PDX and MSM response prediction is substantial under cetuximab and erlotinib: 84% (21/25, P = 0.001) and 80% (20/25, P = 0.003). A total of 5 from the 25 patients have been treated with cetuximab showing a clinical response identical to both predictions.For NSCLC patients, this proof-of-concept study shows a considerable agreement in response prediction from MSM and PDX approaches, but MSM saves time and laboratory resources. Our result indicates the potential of MSM-based approach for clinical decision making when selecting cancer TTs. Clin Cancer Res; 22(9); 2167-76. ©2015 AACR.
Is homelessness a mental health problem?
Authors: E L Bassuk, L Rubin, A Lauriat
Journal: American Journal of Psychiatry (1984)

Seventy-eight homeless men, women, and children staying at an emergency shelter were interviewed. The vast majority were found to have severe psychological illnesses that largely remained untreated. Approximately 91% were given primary psychiatric diagnoses: About 40% had psychoses, 29% were chronic alcoholics, and 21% had personality disorders. Approximately one-third had been hospitalized for psychiatric care. The authors discuss the relationship of mental health policy to the homeless and suggest that shelters have become alternative institutions to meet the needs of mentally ill people who are no longer cared for by departments of mental health.
Reply to Michael Froehner, Rainer Koch, Manfred P. Wirth's Letter to the Editor re: Jesse D. Sammon, Firas Abdollah, Anthony D’Amico, et al. Predicting Life Expectancy in Men Diagnosed with Prostate Cancer. Eur Urol 2015;68:756–65
Authors: Jesse D. Sammon, Firas A Abdollah, Quoc-Dien Trinh
Journal: European Urology (2015)
Atypical Antipsychotic Drugs and the Risk for Acute Kidney Injury and Other Adverse Outcomes in Older Adults
Authors: Y. Joseph Hwang, Stephanie N. Dixon, Jeffrey P. Reiss, Ron Wald, Chirag R. Parikh, Sonja Gandhi, Salimah Z. Shariff, Neesh Pannu, Danielle M. Nash, Faisal Rehman, Amit X. Garg
Journal: Annals of Internal Medicine (2014)

Acute kidney injury (AKI) has been attributed to atypical antipsychotic drugs, such as quetiapine, risperidone, and olanzapine. This population-based, retrospective cohort study of older adults in ...
Liver and Lung Tumors in Mice Exposed at Birth to 4-Dimethylaminoazobenzene or Its 2-Methyl or 3′-Methyl Derivatives1&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Roe, F. J. C., Warwick, G. P., Carter, R. L., Peto, R., Ross, W. C. J., Mitchley, B. C. V., Barron, N. A.
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Liver and Lung Tumors in Mice Exposed at Birth to 4-Dimethylaminoazobenzene or Its 2-Methyl or 3′-Methyl Derivatives1 Get access F. J. C. Roe, F. J. C. Roe Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar G. P. Warwick, G. P. Warwick Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar R. L. Carter, R. L. Carter Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Peto, R. Peto Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar W. C. J. Ross, W. C. J. Ross Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar B. C. V. Mitchley, B. C. V. Mitchley Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar N. A. Barron N. A. Barron Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, London, S.W. 3, England Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 47, Issue 3, September 1971, Pages 593–601, https://doi.org/10.1093/jnci/47.3.593 Published: 01 September 1971 Article history Received: 25 February 1971 Accepted: 21 May 1971 Published: 01 September 1971