tbuckley/cabot-search huggingface dataset:
A novel anti-CD19 monoclonal antibody (GBR 401) with high killing activity against B cell malignancies
Authors: Caroline S Breton, Aimable Nahimana, Dominique Aubry, Julie Macoin, Pierre Moretti, Martin Bertschinger, Samuel Hou, Michel A Duchosal, Jonathan Back
Journal: Journal of Hematology & Oncology (2014)

CD19 is a B cell lineage specific surface receptor whose broad expression, from pro-B cells to early plasma cells, makes it an attractive target for the immunotherapy of B cell malignancies. In this study we present the generation of a novel humanized anti-CD19 monoclonal antibody (mAb), GBR 401, and investigate its therapeutic potential on human B cell malignancies. GBR 401 was partially defucosylated in order to enhance its cytotoxic function. We analyzed the in vitro depleting effects of GBR 401 against B cell lines and primary malignant B cells from patients in the presence or in absence of purified NK cells isolated from healthy donors. In vivo, the antibody dependent cellular cytotoxicity (ADCC) efficacy of GBR 401 was assessed in a B cell depletion model consisting of SCID mice injected with healthy human donor PBMC, and a malignant B cell depletion model where SCID mice are xenografted with both primary human B-CLL tumors and heterologous human NK cells. Furthermore, the anti-tumor activity of GBR 401 was also evaluated in a xenochimeric mouse model of human Burkitt lymphoma using mice xenografted intravenously with Raji cells. Pharmacological inhibition tests were used to characterize the mechanism of the cell death induced by GBR 401. GBR 401 exerts a potent in vitro and in vivo cytotoxic activity against primary samples from patients representing various B-cell malignancies. GBR 401 elicits a markedly higher level of ADCC on primary malignant B cells when compared to fucosylated similar mAb and to Rituximab, the current anti-CD20 mAb standard immunotherapeutic treatment for B cell malignancies, showing killing at 500 times lower concentrations. Of interest, GBR 401 also exhibits a potent direct killing effect in different malignant B cell lines that involves homotypic aggregation mediated by actin relocalization. These results contribute to consolidate clinical interest in developing GBR 401 for treatment of hematopoietic B cell malignancies, particularly for patients refractory to anti-CD20 mAb therapies.
An obscuring cause of wide-anion-gap metabolic acidosis in alcoholic patient: an interesting case
Authors: Leenhapong Navaravong, Paul Sufka, James Bryan Warren
Journal: Journal of the Royal Society of Medicine (2009)

Alcoholic ketoacidosis (AKA) is an under-recognized condition that is seen in alcoholics following abrupt cessation or reduction of alcohol consumption. Symptoms and routine laboratory results are non-specific. The diagnosis of AKA is complicated by the fact that standard tests for ketone detection do not detect β-hydroxy butyrate, the primary ketone present in AKA, and must be measured directly. Patients may have a mixed acid base disorder with a primary wide-anion-gap metabolic acidosis, and concurrent metabolic alkalosis and respiratory alkalosis (triple acid base imbalance). A high index of suspicion should be maintained in all patients with a history of heavy alcohol consumption.
Regional Distribution of Diffusible Tracers and Carbonized Microspheres in the Left Ventricle of Isolated Dog Hearts
Authors: TADA YIPINTSOI, WILLIAM A. DOBBS, PAUL D. SCANLON, THOMAS J. KNOPP, JAMES B. BASSINGTHWAIGHTE
Journal: Circulation Research (1973)

Microspheres of different sizes, 125 I-labeled antipyrine (I-Ap), and 42 KCl or 86 RbCl were injected into the aortic inflow of isolated, Langendorff, perfused, nonworking dogs hearts at blood flows of 1.3-4.8 ml/min g -1 . After 15 seconds to 5 minutes, the left ventricle was sectioned into about 300 ordered pieces, and the amount of each tracer was determined. For all tracers, the relative density of deposition was generally higher in the endocardial region, except in one heart in which the aortic pressure and the total coronary flow were low. The deposition of 42 K and that of I-Ap were essentially similar in three hearts over a large range of regional variation. This finding suggests either that both tracers were distributed in proportion to flow or that a small diminution in relative density of deposition of 42 K in high-flow regions due to lower transcapillary extraction was quantitatively similar to a decrease in the residual fraction of I-Ap in these same regions due to faster washout in the first 15-30 seconds after injection. Large microspheres were deposited preferentially in regions of high flow, exaggerating the apparent heterogeneity of regional flows. The distribution of the smaller microspheres was closer to that for I-Ap or 42 K.
New autoantigens in rheumatoid arthritis (RA): screening 8268 protein arrays with sera from patients with RA
Authors: I Auger, N Balandraud, J Rak, N Lambert, M Martin, J Roudier
Journal: Annals of the Rheumatic Diseases (2008)

To identify new IgG autoantibodies in sera from patients with rheumatoid arthritis (RA).We tested serum samples from 19 patients with RA with given human leukocyte antigen (HLA)-DR genotypes, from 7 patients with spondylarthropathy, 2 patients with lupus, 4 patients with systemic sclerosis and 10 healthy individuals on 8268 human protein arrays.We identified four antigens (peptidyl arginine deiminase 4 (PAD4), protein kinase Cbeta1 (PKCbeta1), phosphatylinositol 4 phosphate 5 kinase type II gamma (PIP4K2C) and v raf murine sarcoma viral oncogene homologue B1 catalytic domain (BRAF)) that were recognised almost uniquely by sera from patients with RA on protein arrays. Using purified proteins, we confirmed that PAD4 and BRAF are recognised almost uniquely by patients with RA.We identified PAD4 and BRAF as RA specific autoantigens.
A blind comparison of the effectiveness of endoscopic ultrasonography and endoscopy in staging early gastric cancer
Authors: H Yanai, T Noguchi, S Mizumachi, H Tokiyama, H Nakamura, M Tada, K Okita
Journal: Gut (1999)

Endoscopic ultrasonography is expected to be useful for invasion depth staging of early gastric cancer. A prospective blind study of the staging characteristics of endoscopy and endoscopic ultrasonography for early gastric cancer was performed.Findings of endoscopy and endoscopic ultrasonography using a 20 MHz thin ultrasound probe were independently reviewed and the results of 52 early gastric cancer lesions analysed.The overall accuracy rates in invasion depth staging of early gastric cancer were 63% for endoscopy and 71% for endoscopic ultrasonography. No statistically significant differences were observed in overall accuracy. Endoscopic ultrasonography tended to overstage, and lesions that were classified as mucosal cancer by endoscopic ultrasonography were very likely (95%) to be limited to the mucosa on histological examination. All 16 lesions staged as mucosal cancer independently but coincidentally by both methods were histologically limited to the mucosa.Endoscopic ultrasonography is expected to compensate for the understaging of lesions with submucosal invasion that are endoscopically staged as mucosal cancer.
Ex Vivo Activated Human Macrophages Improve Healing, Remodeling, and Function of the Infarcted Heart
Authors: Jonathan Leor, Liat Rozen, Adi Zuloff-Shani, Micha S. Feinberg, Yoram Amsalem, Israel M. Barbash, Erez Kachel, Radka Holbova, Yael Mardor, Dianne Daniels, Aharon Ocherashvilli, Arie Orenstein, David Danon
Journal: Circulation (2006)

Background— Activated macrophages have a significant role in wound healing and damaged tissue repair. We sought to explore the ability of ex vivo activated macrophages to promote healing and repair of the infarcted myocardium. Methods and Results— Human activated macrophage suspension (AMS) was prepared from a whole blood unit obtained from young donors in a closed sterile system and was activated by a novel method of hypo-osmotic shock. The AMS (&amp;4×10 5 cells) included up to 43% CD14-positive cells and was injected into the ischemic myocardium of rats (n=8) immediately after coronary artery ligation. The control group (n=9) was treated with saline injection. The human cells existed in the infarcted heart 4 to 7 days after injection, as indicated by histology, human growth hormone-specific polymerase chain reaction, and magnetic resonance imaging (MRI) tracking of iron oxide–nanoparticle-labeled cells. After 5 weeks, scar vessel density (±SE) (25±4 versus 10±1 per mm 2 ; P &lt;0.05), myofibroblast accumulation, and recruitment of resident monocytes and macrophages were greater in AMS-treated hearts compared with controls. Serial echocardiography studies, before and 5 weeks after injection, showed that AMS improved scar thickening (0.15±0.01 versus 0.11±0.01 cm; P &lt;0.05), reduced left ventricular (LV) diastolic dilatation (0.87±0.02 versus 0.99±0.04 cm; P &lt;0.05), and improved LV fractional shortening (31±2 versus 20±4%; P &lt;0.05), compared with controls. Conclusions— Early after myocardial infarction, injection of AMS accelerates vascularization, tissue repair, and improves cardiac remodeling and function. Our work suggests a novel clinically relevant option to promote the repair of ischemic tissue.
Advising parents of asthmatic children on passive smoking: randomised controlled trial
Authors: L. Irvine, I. K Crombie, R. A Clark, P. W Slane, C. Feyerabend, K. E Goodman, J. I Cater
Journal: BMJ (1999)

<h3>Abstract</h3> <b>Objective:</b> To investigate whether parents of asthmatic children would stop smoking or alter their smoking habits to protect their children from environmental tobacco smoke. <b>Design:</b> Randomised controlled trial. <b>Setting:</b> Tayside and Fife, Scotland. <b>Participants:</b> 501 families with an asthmatic child aged 2-12 years living with a parent who smoked. <b>Intervention:</b> Parents were told about the impact of passive smoking on asthma and were advised to stop smoking or change their smoking habits to protect their child9s health. <b>Main outcome measures:</b> Salivary cotinine concentrations in children, and changes in reported smoking habits of the parents 1 year after the intervention. <b>Results:</b> At the second visit, about 1 year after the baseline visit, a small decrease in salivary cotinine concentrations was found in both groups of children: the mean decrease in the intervention group (0.70 ng/ml) was slightly smaller than that of the control group (0.88 ng/ml), but the net difference of 0.19 ng/ml had a wide 95% confidence interval (−0.86 to 0.48). Overall, 98% of parents in both groups still smoked at follow up. However, there was a non-significant tendency for parents in the intervention group to report smoking more at follow up and to having a reduced desire to stop smoking. <b>Conclusions:</b> A brief intervention to advise parents of asthmatic children about the risks from passive smoking was ineffective in reducing their children9s exposure to environmental tobacco smoke. The intervention may have made some parents less inclined to stop smoking. If a clinician believes that a child9s health is being affected by parental smoking, the parent9s smoking needs to be addressed as a separate issue from the child9s health. <h3>Key messages</h3> Many asthmatic children are exposed to high levels of environmental tobacco smoke A brief intervention informing parents of asthmatic children on the harmful effects of passive smoking did not lead to a reduction in exposure of their children to tobacco smoke Low rates of smoking cessation were found in both the intervention group and the control group Some parents may have been less inclined to stop smoking after the intervention Brief interventions requesting smokers to stop for another person9s health seem ineffective
Relationships of Coronary Heart Disease With 27-Hydroxycholesterol, Low-Density Lipoprotein Cholesterol, and Menopausal Hormone Therapy
Authors: Jacques E. Rossouw, Ross L. Prentice, JoAnn E. Manson, Aaron K. Aragaki, Judith Hsia, Lisa W. Martin, Lewis Kuller, Karen C. Johnson, Charles Eaton, Rebecca Jackson, Maurizio Trevisan, Matthew Allison, Ron C. Hoogeveen
Journal: Circulation (2012)

Menopausal hormone therapy (MHT) increases the risk of coronary heart disease (CHD) in older women with elevated low-density lipoprotein (LDLC) levels. The endogenous estrogen receptor antagonist 27-hydroxycholesterol (27OHC) is correlated with LDLC levels and may block the beneficial effects of estrogen on the cardiovascular system.We conducted a nested case-control study in the Women's Health Initiative trials of 350 CHD cases and 813 matched controls to explore potential mediation by 27OHC of the dependence of the CHD risk elevation with MHT on LDLC. Baseline levels of 27OHC were not associated with CHD risk when LDLC was included in the multivariable models. The odds ratio for CHD associated with increased LDLC was 1.15 (95% confidence interval, 1.08-1.23) and was unchanged at 1.14 (95% confidence interval, 1.07-1.22) when 27OHC was added to the model. Baseline 27OHC did not interact with MHT on CHD risk (P=0.81). In contrast, LDLC levels modified the effect of MHT on CHD risk (P for interaction=0.02), and adding 27OHC did not affect this result. With the use of log scales, the effect of MHT on CHD increased linearly with increasing level of baseline LDLC, with a transition from no risk to increased risk at ≈3.36 mmol/L (130 mg/dL).This study found that 27OHC does not independently increase the risk of CHD, does not modify the increased risk of CHD resulting from MHT, and does not mediate the interaction of LDLC with MHT. Measuring blood lipids may aid in counseling individual women about initiating MHT and cardiovascular risk mitigation.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.
STAT3 mutations are frequent in T-cell large granular lymphocytic leukemia with pure red cell aplasia
Authors: Zhi-Yuan Qiu, Lei Fan, Li Wang, Chun Qiao, Yu-Jie Wu, Jian-Feng Zhou, Wei Xu, Jian-Yong Li
Journal: Journal of Hematology & Oncology (2013)

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare lymphoproliferative disorder and can cooccur in the context of pure red cell aplasia (PRCA). The aim of the current study was to analyze the signal transducer and activator of transcription 3 (STAT3) mutation status and its clinical significance in T-LGLL. We found STAT3 mutations in 21.4% of patients with T-LGLL. High β2-MG (β2-microglobulin) levels (P = 0.005), neutropenia (P = 0.018) and PRCA (P = 0.001) all displayed a significant association with STAT3 mutations. In univariate analysis, treatment-free survival (TFS) was affected by STAT3 mutation status (P = 0.008) and β2-MG (P = 0.006). Our results demonstrate the remarkable correlation of STAT3 mutation with PRCA, neutropenia and β2-MG.
Chromosome instability is common in human cleavage-stage embryos
Authors: Evelyne Vanneste, Thierry Voet, Cédric Le Caignec, Michèle Ampe, Peter Konings, Cindy Melotte, Sophie Debrock, Mustapha Amyere, Miikka Vikkula, Frans Schuit, Jean-Pierre Fryns, Geert Verbeke, Thomas D'Hooghe, Yves Moreau, Joris R Vermeesch
Journal: Nature Medicine (2009)
Dual CDK4/CDK6 Inhibition Induces Cell-Cycle Arrest and Senescence in Neuroblastoma
Authors: JulieAnn Rader, Mike R. Russell, Lori S. Hart, Michael S. Nakazawa, Lili T. Belcastro, Daniel Martinez, Yimei Li, Erica L. Carpenter, Edward F. Attiyeh, Sharon J. Diskin, Sunkyu Kim, Sudha Parasuraman, Giordano Caponigro, Robert W. Schnepp, Andrew C. Wood, Bruce Pawel, Kristina A. Cole, John M. Maris
Journal: Clinical Cancer Research (2013)

Neuroblastoma is a pediatric cancer that continues to exact significant morbidity and mortality. Recently, a number of cell-cycle proteins, particularly those within the Cyclin D/CDK4/CDK6/RB network, have been shown to exert oncogenic roles in neuroblastoma, suggesting that their therapeutic exploitation might improve patient outcomes.We evaluated the effect of dual CDK4/CDK6 inhibition on neuroblastoma viability using LEE011 (Novartis Oncology), a highly specific CDK4/6 inhibitor.Treatment with LEE011 significantly reduced proliferation in 12 of 17 human neuroblastoma-derived cell lines by inducing cytostasis at nanomolar concentrations (mean IC50 = 307 ± 68 nmol/L in sensitive lines). LEE011 caused cell-cycle arrest and cellular senescence that was attributed to dose-dependent decreases in phosphorylated RB and FOXM1, respectively. In addition, responsiveness of neuroblastoma xenografts to LEE011 translated to the in vivo setting in that there was a direct correlation of in vitro IC50 values with degree of subcutaneous xenograft growth delay. Although our data indicate that neuroblastomas sensitive to LEE011 were more likely to contain genomic amplification of MYCN (P = 0.01), the identification of additional clinically accessible biomarkers is of high importance.Taken together, our data show that LEE011 is active in a large subset of neuroblastoma cell line and xenograft models, and supports the clinical development of this CDK4/6 inhibitor as a therapy for patients with this disease. Clin Cancer Res; 19(22); 6173-82. ©2013 AACR.
Management of Congestive Heart Failure in Patients With Acute Myocardial Infarction
Authors: Randall Genton
Journal: JAMA (1986)

SEVERE left ventricular dysfunction induced by extensive infarction is the most common cause of in-hospital death in patients with myocardial infarction.1Prompt recognition of the clinical manifestations of congestive heart failure and an aggressive approach to therapy that improves hemodynamic performance but does not exacerbate ischemia is essential.  The rationale for the aggressive management of heart failure in patients with acute infarction is based on the concept that infarction evolves over several hours and factors underlying its complications (eg, expansion, recurrent infarction, and myocardial rupture) over several days. Both the extent and complications of infarction are caused by, and are, determinants of hemodynamic factors influencing the balance between myocardial oxygen consumption and oxygen delivery. Therefore, prompt therapy is thought to reduce the extent of infarction, the probability of recurrent injury, and the propensity to expansion and cardiac rupture. Beneficial effects of treatment may lead to improved left ventricular performance
Partial atrial resection in advanced lung carcinoma with and without cardiopulmonary bypass.
Authors: T Shirakusa, M Kimura
Journal: Thorax (1991)

Combined pneumonectomy and partial resection of the left atrium was performed in 12 patients with advanced lung carcinoma (T3 and T4 in the new UICC classification). In the eight patients with a T3 lung carcinoma intrapericardial atrial resection with vascular clamping was carried out; four of the patients died within a year. The remaining four patients had a T4 tumour and underwent removal of the right lung and part of the left atrium under total cardiopulmonary bypass. One patient died shortly after the operation from cerebral and cerebellar infarction, and one died 11 months later from brain metastases. Two are alive and well. Complete resection appears to offer a chance for longer survival in patients with advanced lung carcinoma that extends directly into the intrapericardial pulmonary vessels or atrium.
Oncogene Mechanism Suggests Novel Therapeutic Approaches To Cancer
Authors: P. A. Newman
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Oncogene Mechanism Suggests Novel Therapeutic Approaches To Cancer Get access Patricia A. Newman Patricia A. Newman Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 17, 5 September 1990, Pages 1383–1384, https://doi.org/10.1093/jnci/82.17.1383 Published: 05 September 1990
Tamoxifen and Aromatase Inhibitors Differentially Affect Vascular Endothelial Growth Factor and Endostatin Levels in Women with Breast Cancer
Authors: Chris E. Holmes, Joe C. Huang, Thomas R. Pace, Alan B. Howard, Hyman B. Muss
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Circulating and cellular proangiogenic and antiangiogenic proteins such as vascular endothelial growth factor (VEGF) and endostatin contribute to the local angiogenic balance. We explored the effects of tamoxifen and aromatase inhibitors on concentrations of VEGF and endostatin in plasma, serum, and platelet releasate (induced by platelet activation). Experimental Design: VEGF and endostatin concentrations were measured with a quantitative immunoassay before and after 1 to 5 weeks of treatment in 30 women with breast cancer treated with either tamoxifen (n = 14) or aromatase inhibitors (n = 16). Platelet activation was induced by a thrombin receptor agonist. Results: Tamoxifen therapy resulted in an increase in platelet releasate concentrations of VEGF (P = 0.01) but no change in plasma VEGF. In contrast, aromatase inhibitor therapy did not affect serum, plasma, or platelet releasate VEGF. In univariate analysis, aspirin use attenuated the tamoxifen-associated increase in VEGF in the platelet releasate and decreased serum levels of VEGF (P = 0.03). Aromatase inhibitor therapy resulted in a decrease in serum endostatin concentrations (P = 0.04), whereas plasma concentrations of endostatin tended to be higher during treatment with aromatase inhibitors (P = 0.06). Tamoxifen therapy resulted in no change in serum or plasma endostatin concentrations. Platelet releasate concentrations of endostatin did not change with either treatment. Interindividual variability was noted among both aromatase inhibitor– and tamoxifen-treated patients. Conclusions: Tamoxifen and aromatase inhibitor therapy affect VEGF and endostatin levels and likely contribute to the angiogenic balance in breast cancer patients. Aspirin decreased the proangiogenic effects of tamoxifen, suggesting that antiplatelet and/or antiangiogenic therapy might improve the effectiveness of tamoxifen in women with breast cancer.