tbuckley/cabot-search huggingface dataset:
FATAL SEPTICEMIA IN MACACUS RHESUS CAUSED BY A STREPTOCOCCUS DECOLORIZED BY GRAM'S METHOD
Authors: R. V. Lamar
Journal: The Journal of Experimental Medicine (1909)

A Gram-negative streptococcus is associated with one form of fatal septicemia arising naturally in Macacus rhesus confined in laboratories. This streptococcus differs from Streptococcus pyogenes in its behavior to Gram's method of staining; in its slight fermentative powers; in the persistence of vitality for a very long time in its cultures; in its high degree of pathogenicity for certain lower animals; and in the preservation of its virulence undiminished for many months when cultivated upon artificial media. In the present state of our knowledge this streptococcus must be considered as not identical with any streptococcus heretofore described.
Denosumab for Prevention of Skeletal-Related Events in Patients With Bone Metastases From Solid Tumors: Incremental Benefit, Debatable Value
Authors: Howard West
Journal: Journal of Clinical Oncology (2011)

avoid this issue, it would be best if we could design trials to be large enough to have power to detect a survival advantage before or even with a crossover.However, this may not be feasible.As an alternative, in the case of a disease such as cancer, where DFS is not only a well-accepted surrogate for survival but also a correlate of quality of life, it will continue to be necessary to develop and use statistical methods that reliably and transparently explore the survival advantage of a new therapy.In the context of the protocol-defined primary outcome analyses of DFS, methods such as IPCW can provide important additional evidence to guide therapeutic choices.In conclusion, for the BIG 1-98 trial, the results from the IPCW analysis of OS, in addition to the ITT analyses for DFS and OS, enlighten the interpretation of the results.Thus, we commend the author's decision to introduce these methods to readers of Journal of Clinical Oncology.Although in this particular case, the refined IPCW estimate of OS may not influence treatment decisions, one can envision situations where it might.Ideally, studies should not require estimation techniques such as this, but rather they should be designed to provide estimates that do not require assumptions or models.However, our responsibility to our clinical trial participants often means that we must forgo the optimal design.In these cases, we must sometimes sacrifice some of the information we had hoped to obtain.The use of methods such as these helps minimize this sacrifice.
Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation
Authors: Shaoke Lou, Heung-Man Lee, Hao Qin, Jing-Woei Li, Zhibo Gao, Xin Liu, Landon L Chan, Vincent KL Lam, Wing-Yee So, Ying Wang, Si Lok, Jun Wang, Ronald CW Ma, Stephen Kwok-Wing Tsui, Juliana CN Chan, Ting-Fung Chan, Kevin Y Yip
Journal: Genome biology (2014)

Abstract Background DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. Results Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. Conclusion Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions.
Brain scan diagnosis of central nervous system involvement in systemic lupus erythematosus.
Authors: R F Tan, D D Gladman, M B Urowitz, N Milne
Journal: Annals of the Rheumatic Diseases (1978)

Twenty-five patients with 29 episodes of active systemic lupus erythematosus with central nervous system involvement were studied according to a uniform protocol. Brain scans were found to be abnormal in all patients studied, and electroencephalograms were abnormal in 20/25 patients. Serial brain scanning was found to be useful in the diagnosis of exacerbations and the monitoring of corticosteroid dosage.
An open trial of interferon alfa recombinant for hepatitis C after liver transplantation: Antiviral effects and risk of rejection
Authors: Cyrille Féray, Didier Samuel, Michèle Gigou, Valérie Paradis, Marie Francoise David, Catherine Lemonnier, Michel Reynès, Henri Bismuth
Journal: Hepatology (1995)

The aim of this open trial was to assess the efficacy and the safety of interferon (IFN) alfa therapy in liver transplant recipients with chronic active hepatitis caused by hepatitis C virus. In July 1991, among 447 liver recipients regularly observed at our institution, 46 had developed HCV-related chronic active hepatitis defined by piece meal necrosis. Fourteen of these 46 patients received IFN alfa 3 mIU three times weekly for a planned duration of 6 months and were compared to the 32 untreated patients. Genotyping and quantification of viremia were performed using type-specific amplification and branched DNA assay. Histological follow-up was available in all patients and routinely before and after IFN therapy. Treated and untreated patients did not differ regarding gender, age, length of follow-up, maximum histological score, and genotypes (41 of 46 were of type 1b). Induction of chronic rejection was observed in 5 of 14 treated patients leading to retransplantation in 3. In contrast, chronic rejection occurred in 1 of 32 untreated patients (P < .005) during the posttransplantation follow-up. Among the 9 treated patients without rejection, a decrease of transaminases or of HCV RNA levels of more than 50% were observed in 8 and 4, respectively; 2 patients had a complete response, and 1 did not relapse after discontinuation of IFN. Histological improvement occurred in 2 of the treated patients and in none of the untreated patients. IFN therapy in liver transplant recipients has poor antiviral effect and can induce chronic rejection. Its use in this setting should be cautious.
Shedding of the Urinary Biomarker Kidney Injury Molecule-1 (KIM-1) Is Regulated by MAP Kinases and Juxtamembrane Region
Authors: Zhiwei Zhang, Benjamin D. Humphreys, Joseph V. Bonventre
Journal: Journal of the American Society of Nephrology (2007)

Kidney injury molecule-1 (KIM-1) is markedly upregulated in renal proximal tubule cells by stimuli that promote dedifferentiation, including ischemic or toxic injury, as well as in cases of tubulointerstitial disease, polycystic kidney disease, and renal cell carcinoma. Structurally, KIM-1 possesses a single transmembrane domain and undergoes membrane-proximal cleavage, which leads to the release of soluble KIM-1 ectodomain into the urine. Urinary KIM-1 ectodomain is a promising sensitive and specific biomarker for acute kidney injury in humans, and therefore it is important to determine what regulates KIM-1 shedding. We found that constitutive cleavage of KIM-1 is mediated by ERK activation, and that cleavage is accelerated by p38 MAP kinase activation. After cleavage, a 14-kD membrane-bound fragment of KIM-1, which contains two highly conserved tyrosine residues, was tyrosine-phosphorylated. Mutagenesis studies demonstrated that the juxtamembrane secondary structure, not the primary amino acid sequence, was critical to the cleavage of KIM-1.
EFFECT OF ETHIONINE-INDUCED PANCREATIC DAMAGE ON IRON ABSORPTION
Authors: Thomas D. Kinney, Nathan Kaufman, Janis Klavins
Journal: The Journal of Experimental Medicine (1955)

Groups of rats were fed a diet of the purified type which was supplemented by dl-ethionine to produce pancreatic damage. It was shown that animals with pancreatic damage absorbed more iron from the gastrointestinal tract than control animals without pancreatic damage. When iron was added to the diet the animals with pancreatic damage absorbed even greater quantities of iron. These findings in rats were corroborated by similar findings in mice.
A prospective cohort study of injury in amateur and professional boxing
Authors: T Zazryn, P Cameron, P McCrory
Journal: British Journal of Sports Medicine (2006)

Background: There is concern over the potential for a high incidence of injury in boxing. This is despite a lack of prospective data evaluating the risk for modern day participants. Updated, reliable data with a focus on potential exposure to injury for both amateur and, especially, professional boxers is required. Aim: To determine the epidemiology of injury and exposure of amateur and professional boxers in Victoria, Australia. Methods: A prospective cohort study with one year follow up was carried out over 2004–2005. Thirty three amateur and 14 active professional boxers registered with either Boxing Victoria Inc (amateurs) or the Professional Boxing and Combat Sports Board of Victoria (professionals) volunteered. Exposure at training and competition was measured, and any injuries sustained during this participation were recorded. Results: Twenty one injuries were sustained by the cohort during the follow up period. Most were to the head region (71%; 95% confidence interval −3.7 to 89.4), with concussion being the most common (33%). An overall injury rate of 2.0 injuries per 1000 hours of boxing was calculated. Conclusion: The high exposure experienced by the boxers (as a result of considerable training time) indicated that boxing has acute injury rates comparable to, and often lower than, those found in other contact and non-contact sports. Further, acute injuries during training appear to be less common and severe than those sustained in bouts.
Steps Forward in the Assessment of Myocardial Viability in Left Ventricular Dysfunction
Authors: James E. Udelson
Journal: Circulation (1998)

he compelling pathophysiology of the states of reversible LV dysfunction, myocardial hibernation, and myocardial stunning have spawned a voluminous literature as clinical investigators attempt to optimize the noninvasive identification of patients with these conditions before consideration of revascularization.Such techniques have direct relevance in patients with clinical syndromes associated with LV dysfunction.This is perhaps most important and most relevant in patients with a clinical syndrome of heart failure and a significant degree of global LV dysfunction, a subset of whom will derive considerable benefit in terms of outcome and recovery of LV function after revascularization.Several studies have now suggested that revascularization in the setting of LV dysfunction and significantly retained myocardial viability is associated with an improved natural history 1-5 as well as improvement in heart failure symptoms and functional capacity. 6Besides providing clinically relevant data, noninvasive scintigraphic and echocardiographic techniques have also helped to illuminate the complex perfusion, metabolic, and functional correlates of these states of reversible LV dysfunction, which remain subjects for debate. 7,
Multicenter Phase II Study of Bendamustine Plus Rituximab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Authors: Ken Ohmachi, Nozomi Niitsu, Toshiki Uchida, Seok Jin Kim, Kiyoshi Ando, Naoki Takahashi, Naoto Takahashi, Naokuni Uike, Hyeon Seok Eom, Yee Soo Chae, Takashi Terauchi, Ukihide Tateishi, Mitsuaki Tatsumi, Won Seog Kim, Kensei Tobinai, Cheolwon Suh, Michinori Ogura
Journal: Journal of Clinical Oncology (2013)

Effective and less aggressive therapies are required for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for or have undergone autologous stem-cell transplantation (ASCT). The present phase II study assessed the efficacy and safety of bendamustine plus rituximab (BR) in this population.Patients with relapsed or refractory DLBCL treated with one to three prior chemotherapy regimens received rituximab 375 mg/m(2) intravenous (IV) infusion on day 1 and bendamustine 120 mg/m(2) by IV infusion on days 2 and 3 of each 21-day cycle for up to six cycles. The primary end point was overall response rate (ORR), and the secondary end points were complete response (CR) rate, progression-free survival (PFS), and safety.Sixty-three patients were enrolled, and 59 received BR. The median age was 67 years (range, 36 to 75 years), and 62.7% of patients were 65 years of age or older. Fifty-seven patients (96.6%) were previously treated with rituximab-containing chemotherapy. The ORR was 62.7% (95% CI, 49.1% to 75.0%), with a CR rate of 37.3% (95% CI, 25.0% to 50.9%). The ORRs were comparable between patients ≥ 65 years of age and less than 65 years (62.2% and 63.6%, respectively). The median PFS was 6.7 months (95% CI, 3.6 to 13.7 months). The most frequently observed grade 3 or 4 adverse events were hematologic: lymphopenia (78.0%), neutropenia (76.3%), leukopenia (72.9%), CD4 lymphopenia (66.1%), and thrombocytopenia (22.0%).BR is a promising salvage regimen for patients with relapsed or refractory DLBCL after rituximab-containing chemotherapy, warranting further investigation.
Erythropoietin: multiple targets, actions, and modifying influences for biological and clinical consideration
Authors: Hal E. Broxmeyer
Journal: The Journal of Experimental Medicine (2013)

Erythropoietin (EPO), a humoral regulator of erythropoiesis and replacement therapy for selected red blood cell disorders in EPO-deficient patients, has been implicated in a wide range of activities on diverse cell, tissue, and organ types. EPO signals via two receptors, one comprising EPO receptor (EPOR) homodimers and the other a heterodimer of EPOR and CD131—the common β chain component of the GM-CSF, interleukin (IL)-3, and IL-5 receptors. Ligation of EPORs triggers various signaling pathways, including the JAK2–STAT5 and MAPK–NF-κB pathways, depending both on the receptor and the target cell type. A new study in this issue reveals a novel EPO-triggered pathway involving a Spi2A serpin–lysosome–cathepsin cascade that is initiated through the homodimeric EPOR complex and is required for the survival of erythroid progenitors. A full understanding of EPO’s effects on various cell types and their potential clinical relevance requires more work on the signaling events initiated through both EPORs, the effects of other cytokines and growth factors that modulate EPO’s actions, and a comparison of the effects of full-length versus truncated forms of EPO.
The effect of membrane stabilizing agents on induction of the immune response. I. Effect of lymphocyte activation in mixed lymphocyte reactions.
Authors: J D Waterfield, L Hammarström, E Smith
Journal: The Journal of Experimental Medicine (1976)

The effect of three membrane-stabilizing agents, chlorpromazine, imipramine, and lidocain, on in vitro activation of cellular responses was studied using the one-way MLR. Cellular activation was found to be depressed by these drugs. However, the degree of suppression paralleled the decline of viable cells in the cultures. It is concluded that drug-induced inhibition of MLR was due solely to the toxicity of the compounds.
Dr. Wagner and Colleagues Reply
Authors: KAREN DINEEN WAGNER, ROBERT A. KOWATCH, GRAHAM J. EMSLIE, ROBERT L. FINDLING, TIMOTHY E. WILENS, KEVIN McCAGUE, JOSEPH D’SOUZA, ARTUR WAMIL, ROBERT B. LEHMAN, DOUGLAS BERV, DAVID LINDEN
Journal: American Journal of Psychiatry (2006)
The Pharmacodynamic Effects of Mepolizumab, a Humanized Monoclonal Antibody Against IL-5, in Pediatric Patients with Eosinophilic Esophagitis: A Randomized, Double-blind, Controlled Clinical Trial
Authors: A. Assa'ad, S. Aceves, S. Gupta, É. Drouin, M. Collins, C. Jurgensen, A. Heath, T. Perschy, J. Patel, H. Ortega
Journal: Journal of Allergy and Clinical Immunology (2010)
Clinical control of asthma associates with measures of airway inflammation
Authors: Franke Volbeda, Martine Broekema, Monique E Lodewijk, Machteld N Hylkema, Helen K Reddel, Wim Timens, Dirkje S Postma, Nick H T ten Hacken
Journal: Thorax (2012)

<h3>Background</h3> Control of asthma is the goal of asthma management worldwide. The Global Initiative for Asthma defined control by a composite measure of clinical findings and future risk but without using markers of airway inflammation, the hallmark of asthma. We investigated whether clinical asthma control reflects eosinophilic inflammation in a broad population. <h3>Methods</h3> Control of asthma was assessed over a period of 4 weeks in 111 patients with asthma: 22 totally controlled, 47 well controlled and 42 uncontrolled. Lung function, quality of life, airway hyperresponsiveness to AMP, sputum and blood eosinophils, exhaled nitric oxide (NO) and bronchial biopsies were obtained. <h3>Results</h3> The 69 subjects with controlled asthma (totally and well controlled combined) had lower median blood eosinophil numbers, slope of AMP hyperresponsiveness, and alveolar NO levels than the 42 subjects with uncontrolled asthma: 0.18 (range 0.01–0.54) versus 0.22 (0.06–1.16)×10<sup>9</sup>/litre (p&lt;0.05), 3.8 (−0.4–17 750) versus 39.7 (0.4–28 000) mg/ml (p&lt;0.05) and 5.3 (1.5–14.9) versus 6.7 (2.6–51.7) ppb (p&lt;0.05) respectively. Biopsies from subjects with controlled asthma contained fewer eosinophilic granules and more intact epithelium than uncontrolled subjects: 113 (6–1787) versus 219 (19–5313) (p&lt;0.05) and 11.8% (0–65.3) versus 5.6% (0–47.6) (p&lt;0.05) respectively. Controlled asthmatics had better Asthma Quality of Life Questionnaire scores than uncontrolled patients: 6.7 (5.0–7.0) versus 5.9 (3.7–7.0) (p&lt;0.001). <h3>Conclusions</h3> The level of asthma control, based on a composite measure of clinical findings, is associated with inflammatory markers, particularly eosinophilic inflammation, with little difference between totally controlled and well controlled asthma.
Comment on “Characterization of Circulating Endothelial Cells in Acute Myocardial Infarction”
Authors: Jean-françois Vendrell, Renaud Cezar, Kyriakos Lobotesis, Jean-Pierre Vendrell
Journal: Science Translational Medicine (2012)

The circulating endothelial cell population characterized by Damani et al . might be contaminated by endothelium damage after femoral catheterization.
Prognostic Significance of Overexpression and Phosphorylation of Epidermal Growth Factor Receptor (EGFR) and the Presence of Truncated EGFRvIII in Locoregionally Advanced Breast Cancer
Authors: Yago Nieto, Fatima Nawaz, Roy B. Jones, Elizabeth J. Shpall, Samia Nawaz
Journal: Journal of Clinical Oncology (2007)

Purpose The prognostic value of the epidermal growth factor receptor (EGFR) in breast cancer and more specifically, in patients with locoregionally advanced disease, is still undefined. We hypothesized that EGFR status plays a major prognostic role in this setting, through expression, activation, or the presence of its mutated variant EGFRvIII. Patients and Methods We reviewed tumor samples of 225 patients treated uniformly in prospective trials of high-dose chemotherapy for four to nine positive axillary nodes, ≥ 10 positive nodes, or inflammatory carcinoma, and observed for a median of 9 years (range, 3 to 13 years). We analyzed the effect on outcome of expression of EGFR, phosphorylated EGFR (phospho-EGFR), and EGFRvIII, as studied by immunohistochemistry. Results EGFR expression, phospho-EGFR, and mutated EGFRvIII were detected in 43%, 54%, and 4% of the patients, respectively. EGFR expression correlated with negative hormone receptor status, and was associated with significantly worse relapse-free survival (59% v 79%; P &lt; .001) and overall survival (61% v 81%; P = .001) than no expression. There was no association of phospho-EGFR or EGFRvIII with outcome. Multivariate models confirmed the prognostic effect of EGFR independent of other known prognostic variables in this population. The prognostic value of EGFR was most prominent in the human epidermal growth factor receptor 2 (HER-2) –positive and the estrogen receptor/progesterone receptor–negative subgroups. Conclusion EGFR expression, but not phospho-EGFR or EGFRvIII expression, is an independent adverse prognostic factor in patients with high-risk primary breast cancer, particularly when it is coexpressed with HER-2. Our results suggest the potential benefit of dual EGFR/HER-2 receptor targeting in this setting.
The Uses of Penicillin and Streptomycin
Journal: JAMA (1949)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal