tbuckley/cabot-search huggingface dataset:
Thromboxane is produced in response to intracoronary infusions of complement C5a in pigs. Cyclooxygenase blockade does not reduce the myocardial ischemia and leukocyte accumulation.
Authors: B R Ito, D M Roth, D E Chenoweth, A M Lefer, R L Engler
Journal: Circulation Research (1989)

Activated polymorphonuclear leukocytes (PMNs) contribute to myocardial injury during ischemia and reperfusion. There is evidence that activation of the complement pathway may be one of the mechanisms of PMN activation during ischemia. Intracoronary infusion of complement C5a during normal perfusion pressure is associated with decreased coronary flow, contractile dysfunction, and PMN accumulation. The mechanisms responsible for these changes have not been identified. Thromboxane A2 (TXA2) is a potential mediator of this myocardial ischemic response. Activated PMNs produce TXA2, a known coronary vasoconstrictor, and TXA2 was shown to be a mediator of the pulmonary hypertensive response to activated complement. The goal of the present study was to determine if an enhanced TXA2 production is associated with the myocardial response to C5a and whether cyclooxygenase blockade would reduce the myocardial ischemia. In open-chest pigs, intracoronary C5a (500 ng) caused reversible reductions in blood flow (50.0% of control), regional contractile function (25.8% of control), leukocyte trapping (1.0 x 10(6) cells/g myocardium or a peak artery-coronary venous difference of 5.3 x 10(3) cells/microliters blood), and increased coronary venous TXB2 (the TXA2 breakdown product) from 1.6 pmol/ml to a peak of 6.9 pmol/ml. Cyclooxygenase blockade with aspirin or indomethacin, which prevented TXB2 production, did not alter the response in flow, function, or PMN trapping. Ibuprofen, a known direct inhibitor of PMNs in addition to its cyclooxygenase blockade effect, reduced the response slightly. The pig coronary vascular bed was responsive to the TXA2 agonist U46619, which reduced flow and function without PMN trapping. Mechanical reductions in coronary flow to levels equivalent to those during the C5a infusions did not increase coronary venous TXB2 nor cause PMN trapping but did cause equivalent contractile dysfunction. Incubation of whole blood with C5a at concentrations equivalent to those achieved in vivo did not cause TXB2 production. We conclude that 1) TXA2 is produced in response to intracoronary C5a and 2) cyclooxygenase blockade does not prevent the C5a-induced myocardial ischemia, contractile dysfunction, and PMN trapping. The TXA2 production likely involves a vascular site or a blood cell-vascular interaction. This model system indicates the potential for persistently activated PMNs to cause continued ischemia during myocardial reperfusion.
Survivin, bcl-2, bax, and bcl-X Gene Expression in Sentinel Lymph Nodes From Melanoma Patients
Authors: Angela Gradilone, Paola Gazzaniga, Diego Ribuffo, Susanna Scarpa, Emanuele Cigna, Fortunata Vasaturo, Ugo Bottoni, Daniele Innocenzi, Stefano Calvieri, Nicolo’ Scuderi, Luigi Frati, Anna Maria Aglianò
Journal: Journal of Clinical Oncology (2003)

The expression of apoptosis-related genes, such as survivin, bcl-2, bcl-X, and bax, has been evaluated by reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry in sentinel lymph nodes (SLNs) from melanoma patients and then correlated to the outcome of patients.Thirty-six SLNs were examined. After RNA extraction, an RT-PCR followed by Southern blot hybridization was performed to detect survivin, bcl-2, bcl-X, and bax mRNA. bcl-2, survivin, and bax gene expression was evaluated, whenever possible, also by immunohistochemistry at the protein level.We found a significant correlation (P <.005) between survivin expression and outcome of patients; in fact, 61.5% of patients expressing survivin gene progressed or died because of the disease, whereas 38.5% are currently disease-free. Among patients negative for survivin expression, 100% are disease-free after a median follow-up time of 52.9 months. We did not find a significant correlation between bcl-2, bax, and bcl-X gene expression and outcome of patients. In fact, these genes were found equally expressed in patients with disease progression and in disease-free patients.Our findings show a variable expression of apoptosis-related genes in SLNs of melanoma patients; more interestingly, we found that survivin expression correlates to outcome of patients in a statistically significant way, whereas the expression of other genes, such as bcl-2, bax, and bcl-X, did not seem to correlate to progression of disease. We suggest that the detection of survivin gene expression by RT-PCR in SLNs may be a useful prognostic indicator.
Dual Action of Neutrophil Gelatinase–Associated Lipocalin
Authors: Kai M. Schmidt-Ott, Kiyoshi Mori, Jau Yi Li, Avtandil Kalandadze, David J. Cohen, Prasad Devarajan, Jonathan Barasch
Journal: Journal of the American Society of Nephrology (2007)

Neutrophil gelatinase-associated lipocalin (NGAL) is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL exerts bacteriostatic effects, which are explained by its ability to capture and deplete siderophores, small iron-binding molecules that are synthesized by certain bacteria as a means of iron acquisition. Consistently, NGAL deficiency in genetically modified mice leads to an increased growth of bacteria. However, growing evidence suggests effects of the protein beyond fighting microorganisms. NGAL acts as a growth and differentiation factor in multiple cell types, including developing and mature renal epithelia, and some of this activity is enhanced in the presence of siderophore:iron complexes. This has led to the hypothesis that eukaryotes might synthesize siderophore-like molecules that bind NGAL. Accordingly, NGAL-mediated iron shuttling between the extracellular and intracellular spaces may explain some of the biologic activities of the protein. Interest in NGAL has been sparked by the observation that NGAL is massively upregulated after renal tubular injury and may participate in limiting kidney damage. This review summarizes the current knowledge about the dual effects of NGAL as a siderophore:iron-binding protein and as a growth factor and examines the role of these effects in renal injury.
Activation of Receptor for Advanced Glycation End Products
Authors: Ann Marie Schmidt, Shi Du Yan, Jean-Luc Wautier, David Stern
Journal: Circulation Research (1999)

Abstract —Receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily of cell surface molecules and engages diverse ligands relevant to distinct pathological processes. One class of RAGE ligands includes glycoxidation products, termed advanced glycation end products, which occur in diabetes, at sites of oxidant stress in tissues, and in renal failure and amyloidoses. RAGE also functions as a signal transduction receptor for amyloid β peptide, known to accumulate in Alzheimer disease in both affected brain parenchyma and cerebral vasculature. Interaction of RAGE with these ligands enhances receptor expression and initiates a positive feedback loop whereby receptor occupancy triggers increased RAGE expression, thereby perpetuating another wave of cellular activation. Sustained expression of RAGE by critical target cells, including endothelium, smooth muscle cells, mononuclear phagocytes, and neurons, in proximity to these ligands, sets the stage for chronic cellular activation and tissue damage. In a model of accelerated atherosclerosis associated with diabetes in genetically manipulated mice, blockade of cell surface RAGE by infusion of a soluble, truncated form of the receptor completely suppressed enhanced formation of vascular lesions. Amelioration of atherosclerosis in these diabetic/atherosclerotic animals by soluble RAGE occurred in the absence of changes in plasma lipids or glycemia, emphasizing the contribution of a lipid- and glycemia-independent mechanism(s) to atherogenesis, which we postulate to be interaction of RAGE with its ligands. Future studies using mice in which RAGE expression has been genetically manipulated and with selective low molecular weight RAGE inhibitors will be required to definitively assign a critical role for RAGE activation in diabetic vasculopathy. However, sustained receptor expression in a microenvironment with a plethora of ligand makes possible prolonged receptor stimulation, suggesting that interaction of cellular RAGE with its ligands could be a factor contributing to a range of important chronic disorders.
Severe recalcitrant pyoderma gangrenosum treated with infliximab
Authors: M.R. Kaur, H.M. Lewis
Journal: British Journal of Dermatology (2005)

Conflicts of interest: none declared. Sir, We previously reported a case of a 17‐year‐old gentleman with severe recalcitrant pyoderma gangrenosum (PG), who was successfully treated with a combination of mycophenolate mofetil (MMF) and ciclosporin.1 This is an update on this patient's progress, 6 years later. Following complete healing of the PG ulcers affecting the right posterior thigh, immunosuppression was weaned down over 15 months, with only one relapse. He was off treatment for 16 months before he developed a recurrence of the ulceration on the right thigh and a new area of ulceration on the right posterior calf (Fig. 1). Despite recommencing immunosuppressants including prednisolone 25 mg daily, MMF 2 g daily and ciclosporin 6 mg kg−1 day−1, he developed progressive ulceration and we decided to treat him with infliximab. Repeat screening investigations including comprehensive gastrointestinal investigations failed to reveal any underlying cause for the recurrent PG. A dramatic response was seen following three infusions of infliximab given one month apart, at a dose of 3 mg kg−1 (Fig. 2). This resulted in the complete remission of the PG over a 4‐month period. Following the initial infusion a 50% reduction in the size of the ulcers was achieved within 7 days. Treatment was well tolerated with no adverse reactions noted. Ciclosporin and prednisolone were gradually withdrawn with no signs of recurrence of PG at 6 months follow‐up. He remains on MMF 1·5 g daily. Regular wound examination and swabs revealed no evidence of any secondary infection.
Phase I/II Study of Imatinib Mesylate for Recurrent Malignant Gliomas: North American Brain Tumor Consortium Study 99-08
Authors: Patrick Y. Wen, W.K. Alfred Yung, Kathleen R. Lamborn, Patricia L. Dahia, Yanfeng Wang, Bin Peng, Lauren E. Abrey, Jeffrey Raizer, Timothy F. Cloughesy, Karen Fink, Mark Gilbert, Susan Chang, Larry Junck, David Schiff, Frank Lieberman, Howard A. Fine, Minesh Mehta, H. Ian Robins, Lisa M. DeAngelis, Morris D. Groves, Vinay K. Puduvalli, Victor Levin, Charles Conrad, Elizabeth A. Maher, Kenneth Aldape, Michael Hayes, Laurie Letvak, Merrill J. Egorin, Renaud Capdeville, Richard Kaplan, Anthony J. Murgo, Charles Stiles, Michael D. Prados
Journal: Clinical Cancer Research (2006)

Phase I: To determine the maximum tolerated doses, toxicities, and pharmacokinetics of imatinib mesylate (Gleevec) in patients with malignant gliomas taking enzyme-inducing antiepileptic drugs (EIAED) or not taking EIAED. Phase II: To determine the therapeutic efficacy of imatinib.Phase I component used an interpatient dose escalation scheme. End points of the phase II component were 6-month progression-free survival and response.Fifty patients enrolled in the phase I component (27 EIAED and 23 non-EIAED). The maximum tolerated dose for non-EIAED patients was 800 mg/d. Dose-limiting toxicities were neutropenia, rash, and elevated alanine aminotransferase. EIAED patients received up to 1,200 mg/d imatinib without developing dose-limiting toxicity. Plasma exposure of imatinib was reduced by approximately 68% in EIAED patients compared with non-EIAED patients. Fifty-five non-EIAED patients (34 glioblastoma multiforme and 21 anaplastic glioma) enrolled in the phase II component. Patients initially received 800 mg/d imatinib; 15 anaplastic glioma patients received 600 mg/d after hemorrhages were observed. There were 2 partial response and 6 stable disease among glioblastoma multiforme patients and 0 partial response and 5 stable disease among anaplastic glioma patients. Six-month progression-free survival was 3% for glioblastoma multiforme and 10% for anaplastic glioma patients. Five phase II patients developed intratumoral hemorrhages.Single-agent imatinib has minimal activity in malignant gliomas. CYP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure of imatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors. The evaluation of the activity of combination regimens incorporating imatinib is under way in phase II trials.
Prevention and Treatment of Experimental Autoimmune Encephalomyelitis by Soluble CD83
Authors: Elisabeth Zinser, Matthias Lechmann, Antje Golka, Manfred B. Lutz, Alexander Steinkasserer
Journal: The Journal of Experimental Medicine (2004)

CD83 is up-regulated on the surface of dendritic cells (DCs) during maturation and has been widely used as a marker for mature DCs. Recently, we reported the recombinant expression of the extracellular immunoglobulin domain of human CD83 (hCD83ext). Using this soluble form of CD83, allogeneic as well as specific cytotoxic T lymphocyte proliferation could be blocked in vitro. Here we report the functional analysis of soluble CD83 in vivo, using murine experimental autoimmune encephalomyelitis (EAE) as a model. Strikingly, only three injections of soluble CD83 prevented the paralysis associated with EAE almost completely. In addition, even when the EAE was induced a second time, CD83-treated mice were protected, indicating a long-lasting suppressive effect. Furthermore, soluble CD83 strongly reduced the paralysis in different therapeutic settings. Most important, even when the treatment was delayed until the disease symptoms were fully established, soluble CD83 clearly reduced the paralyses. In addition, also when EAE was induced a second time, soluble CD83-treated animals showed reduced disease symptoms. Finally, hCD83ext treatment almost completely reduced leukocyte infiltration in the brain and in the spinal cord. In summary, this work strongly supports an immunosuppressive role of soluble CD83, thereby indicating its therapeutic potential in the regulation of immune disorders in vivo.
Periodontal herpesviruses: prevalence, pathogenicity, systemic risk
Authors: Jørgen Slots
Journal: Periodontology 2000 (2015)

Abstract Periodontitis is an infectious/inflammatory disease characterized by the loss of periodontal ligament and alveolar bone. Herpesviruses are frequent inhabitants of periodontitis lesions, and the periodontopathogenicity of these viruses is the topic of this review. In 26 recent studies from 15 countries, subgingival cytomegalovirus, Epstein–Barr virus and herpes simplex virus type 1, respectively, yielded median prevalences of 49%, 45% and 63% in aggressive periodontitis, 40%, 32% and 45% in chronic periodontitis, and 3%, 7% and 12% in healthy periodontium. An active herpesvirus infection of the periodontium exhibits site specificity, is a potent stimulant of cellular immunity, may cause upgrowth of periodontopathic bacteria and tends to be related to disease‐active periodontitis. Pro‐inflammatory cytokines induced by the herpesvirus infection may activate matrix metalloproteinases and osteoclasts, leading to breakdown of the tooth‐supportive tissues. The notion that a co‐infection of herpesviruses and specific bacteria causes periodontitis provides a plausible etiopathogenic explanation for the disease. Moreover, herpesvirus virions from periodontal sites may dislodge into saliva or enter the systemic circulation and cause diseases beyond the periodontium. Periodontal treatment can diminish significantly the periodontal load of herpesviruses, which may lower the incidence and magnitude of herpesvirus dissemination within and between individuals, and subsequently the risk of acquiring a variety of medical diseases. Novel and more effective approaches to the prevention and treatment of periodontitis and related diseases may depend on a better understanding of the herpesvirus–bacteria–immune response axis.
Predicting Bacteremia in Patients with Community-Acquired Pneumonia
Authors: Mark L. Metersky, Allen Ma, Dale W. Bratzler, Peter M. Houck
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

It is recommended that blood cultures be performed on all patients admitted to the hospital with pneumonia. Questions regarding the cost-effectiveness of this practice have emerged. We used data on 13,043 Medicare patients hospitalized with pneumonia to determine predictors of bacteremia. Predictors included recent antibiotic treatment, liver disease, and three vital-sign and three laboratory abnormalities. Patients were stratified into three groups on the basis of the likelihood of bacteremia. We then created a decision support tool that recommends performing no blood cultures on patients with low likelihood of bacteremia, one blood culture on patients with moderate likelihood of bacteremia, and two blood cultures on patients with higher likelihood of bacteremia. This tool was then applied to a validation cohort of 12,771 patients with pneumonia. Use of the decision support tool would result in 38% fewer blood cultures being performed when compared with the standard practice of performing two blood cultures for each patient and identified 88 to 89% of patients with bacteremia. A simplified tool performed similarly overall but was less sensitive than was the first tool among pneumonia severity index Class V patients. These tools may allow clinicians to target patients with pneumonia in whom blood cultures are most likely to yield a pathogen.
Inducible Activation of c-Myc in Adult Myocardium In Vivo Provokes Cardiac Myocyte Hypertrophy and Reactivation of DNA Synthesis
Authors: Guishan Xiao, Songyan Mao, Georg Baumgarten, Jennifer Serrano, Maria C. Jordan, Kenneth P. Roos, Michael C. Fishbein, W. Robb MacLellan
Journal: Circulation Research (2001)

c-Myc, a protooncogene, mediates both proliferative and cellular growth in many cell types. Although not expressed in the adult heart under normal physiological conditions, Myc expression is rapidly upregulated in response to hypertrophic stimuli. Although Myc is capable of sustaining hyperplastic growth in fetal myocytes, the effects of its re-expression in adult postmitotic myocardium and its role in mediating cardiac hypertrophy are unknown. To determine the effects of de novo Myc activity in adult postmitotic myocardium in vivo, we created a novel transgenic model in which Myc is expressed and inducibly activated specifically in cardiac myocytes. Activation of Myc in adult myocardium was sufficient to reproduce the characteristic changes in myocyte size, protein synthesis, and cardiac-specific gene expression seen in cardiac hypertrophy. Despite the increased cardiac mass, left ventricular function remained normal. Activation of Myc also provoked cell cycle reentry in postmitotic myocytes, which led to increased nuclei per myocyte and DNA content per nuclei.
Predictors of Readmission for Complications of Coronary Artery Bypass Graft Surgery
Authors: Edward L. Hannan
Journal: JAMA (2003)

Risk factors for perioperative mortality after coronary artery bypass graft (CABG) surgery have been extensively studied. However, which factors are associated with early readmissions following CABG surgery are less clear.To identify significant predictors of readmission within 30 days following CABG surgery.Causes for readmission within 30 days were investigated for all patients discharged after CABG surgery in the state of New York from January 1, 1999, through December 31, 1999. A variety of patient demographics, preoperative risk factors, complications, operative and postoperative factors, and provider characteristics were considered as potential predictors of readmissions.Hospital readmissions within 30 days of discharge following CABG surgery.Of 16 325 total patients, 2111 (12.9%) were readmitted within 30 days for reasons related to CABG surgery. The most common causes of readmission were postsurgical infection (n = 598 [28%]) and heart failure (n = 331 [16%]). Eleven risk factors were found to be independently associated with higher readmission rates: older age, female sex, African American race, greater body surface area, previous myocardial infarction within 1 week, and 6 comorbidities. After controlling for these preoperative patient-level risk factors, 2 provider characteristics (annual surgeon CABG volume <100, hospital risk-adjusted mortality rate in the highest decile) and 2 postoperative factors (discharge to nursing home or rehabilitation/acute care facility, length of stay during index CABG admission of > or =5 days) were also related to higher readmission rates.Readmission within 30 days following discharge is an important adverse outcome of CABG surgery. Continued attempts should be made to explore the potential of readmission as a supplement to mortality in assessing provider quality.
Ethnographic evidence of unique hues and elemental colors
Authors: Robert E. MacLaury
Journal: Behavioral and Brain Sciences (1997)

Contrary to argument that unique hues are undemonstrated, the World Color Survey shows that speakers of more than 100 minor and tribal languages focus color categories predominantly on 4 of the 40 hue columns of the ethnographic Munsell array. The pattern is not conditioned by saturation levels or other arbitrary structures among the color chips, nor is Western influence likely to be the cause. Moreover, all evidence suggests that color cognition is autonomous despite the connotations and polysemies of color terms.
Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts.
Authors: L J Joseph, L C Chang, D Stamenkovich, V P Sukhatme
Journal: Journal of Clinical Investigation (1988)

Transfection of an activated rat oncogene into NIH3T3 fibroblasts leads to transformation and induction of a metastatic phenotype. To identify genes whose activation might mediate these processes, we used a differential screening strategy. A 1.5-kb transcript is induced fiftyfold, constitutes 1% of ras transformed cell messenger RNA (mRNA) and is the most abundantly induced message in these cells. Our sequence data shows that it encodes murine cathepsin L, a potent collagenolytic and elastinolytic lysosomal enzyme. The murine clone was used to isolate human cathepsin L complementary DNA (cDNA) clones. The complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L are presented and compared to other papain family cysteine proteinases. Northern analysis shows that both human and murine cathepsin L probes hybridize to a 1.5-kb transcript in several tissues, but also to a 4-kb transcript in human kidney. These clones will facilitate studies of the structure, expression, and function of cathepsin L, including its unexpected upregulation in transformation.