tbuckley/cabot-search huggingface dataset:
Arthritis in a human T lymphotropic virus type I (HTLV-I) carrier.
Authors: S Ijichi, T Matsuda, I Maruyama, T Izumihara, K Kojima, T Niimura, Y Maruyama, S Sonoda, A Yoshida, M Osame
Journal: Annals of the Rheumatic Diseases (1990)

The case is described of a 57 year old woman with polyarthritis fulfilling the 1987 revised criteria of the American Rheumatism Association for rheumatoid arthritis, accompanied by clinical carrier state infection of HTLV-I. Anti-HTLV-I IgM antibodies were detected by western blot analysis in her synovial fluid and serum. Atypical lymphocytes with nuclear convolutions were found in synovial fluid and synovial tissue obtained from the affected knee joint, suggesting in situ activation of HTLV-I infected lymphocytes in the affected synovial compartment. The HTLV-I antigens were detected (1.2%) in short term cultured synovial fluid lymphocytes, by indirect immunofluorescence. These findings supported the possibility that HTLV-I has a role in triggering or modifying inflammation in the synovial compartment.
Maximal respiratory pressures and pulmonary function in male runners.
Authors: L Cordain, B J Glisan, R W Latin, A Tucker, J M Stager
Journal: British Journal of Sports Medicine (1987)

To determine the effects of long term exercise on respiratory muscle strength, maximal inspiratory (Pl max) and expiratory (PE max) pressures, pulmonary volumes and capacities and anthropometric parameters were measured in a group of 101 male runners aged 16 to 58 years. The runners exhibited significantly (p less than 0.05) lower PE max (202 +/- 41 cm H2O and significantly greater residual lung volumes (RV) (2.08 +/- 0.49 L) than predicted values for normal subjects of similar height and age. Forced vital capacities were not different (p greater than 0.05) from values reported for normal non-smoking populations. These data suggest that running may cause a non-pathological increase in RV, perhaps mediated by reductions in expiratory muscle strength. Additionally, current RV regression equations developed for normal subjects may be inappropriate for use in running populations.
Use of Cardiac Biomarkers in End-Stage Renal Disease
Authors: Angela Yee-Moon Wang, Kar-Neng Lai
Journal: Journal of the American Society of Nephrology (2008)

Mortality among patients with ESRD remains high because of an excessive cardiovascular risk related to a very high incidence of cardiac hypertrophy, cardiomyopathy, heart failure, and coronary artery disease. Identifying serum biomarkers that are useful in profiling cardiovascular risk and enabling stratification of early mortality and cardiovascular risk is an important goal in the treatment of these patients. This review examines current evidence pertaining to the role and utility of two emerging cardiac biomarkers, B-type natriuretic peptide and cardiac troponin T, in patients with ESRD. Together, these data demonstrate how these two cardiac biomarkers may play an adjunctive role to echocardiography in assessing cardiovascular risk and how they may aid in the clinical treatment of these patients.
Stability and Diversity of T Cell Receptor Repertoire Usage during Lymphocytic Choriomeningitis Virus Infection of Mice
Authors: Meei  Yun Lin, Raymond M. Welsh
Journal: The Journal of Experimental Medicine (1998)

Numerous studies have examined T cell receptor (TCR) usage of selected virus-specific T cell clones, yet little information is available regarding the stability and diversity of TCR repertoire usage during viral infections. Here, we analyzed the Vβ8.1 TCR repertoire directly ex vivo by complementarity-determining region 3 (CDR3) length spectratyping throughout the acute lymphocytic choriomeningitis virus (LCMV) infection, into memory, and under conditions of T cell clonal exhaustion. The Vβ8 population represented 30–35% of the LCMV-induced CD8+ T cells and included T cells recognizing several LCMV-encoded peptides, allowing for a comprehensive study of a multiclonal T cell response against a complex antigen. Genetically identical mice generated remarkably different T cell responses, as reflected by different spectratypes and different TCR sequences in same sized spectratype bands; however, a conserved CDR3 motif was found within some same sized bands. This indicated that meaningful studies on the evolution of the T cell repertoire required longitudinal studies within individual mice. Such longitudinal studies with peripheral blood lymphocyte samples showed that (a) the virus-induced T cell repertoire changes little during the apoptosis period after clearance of the viral antigens; (b) the LCMV infection dramatically skews the host T cell repertoire in the memory state; and (c) continuous selection of the T cell repertoire occurs under conditions of persistent infections.
Dynamic Monitoring of Oncolytic Adenovirus In Vivo by Genetic Capsid Labeling
Authors: Long P. Le, Helen N. Le, Igor P. Dmitriev, Julia G. Davydova, Tatyana Gavrikova, Seiji Yamamoto, David T. Curiel, Masato Yamamoto
Journal: JNCI Journal of the National Cancer Institute (2006)

Conditionally replicative adenoviruses represent a promising strategy to address the limited efficacy and safety issues associated with conventional cancer treatment. Despite rapid translation into human clinical trials and demonstrated safety, the fundamental properties of oncolytic adenovirus replication and spread and host-vector interactions in vivo have not been completely evaluated.We developed a noninvasive dynamic monitoring system to detect adenovirus replication. We constructed capsid-labeled E1/E3-deleted and wild-type adenoviruses (Ad-wt) by fusing the minor capsid protein IX with red fluorescent proteins mRFP1 and tdimer2(12), resulting in Ad-IX-mRFP1, Ad-IX-tdimer2(12), and Ad-wt-IX-mRFP1. Virus DNA replication, encapsidation, cytopathic effect, thermostability, and binding to primary receptor (coxsackie adenovirus receptor) were analyzed using real-time quantitative polymerase chain reaction, cell viability (MTS) assay, and fluorescence microscopy. Athymic mice (n = 4) carrying xenograft tumors that were derived from A549 lung adenocarcinoma cells were intratumorally inoculated with Ad-wt-IX-mRFP1, and adenovirus replication was dynamically monitored with a fluorescence noninvasive imaging system. Correlations between fluorescence signal intensity and viral DNA synthesis and replication were calculated using Pearson's correlation coefficient (r).The red fluorescence label had little effect on viral DNA replication, encapsidation, cytopathic effect, thermostability, and coxsackie adenovirus receptor binding. The fluorescent signal correlated with viral DNA synthesis and infectious progeny production both in vitro and in vivo (in A549 cells, r = .99 and r = .65; in tumors, r = .93 and r = .92, respectively). The replication efficiency of Ad-wt-IX-mRFP1 in vivo was variable, and replication and viral spreading and persistence were limited, consistent with clinical observations.Genetic capsid labeling provides a promising approach for the dynamic assessment of oncolytic adenovirus function in vivo.
Role of Mitochondrial Dysfunction in Insulin Resistance
Authors: Jeong-a Kim, Yongzhong Wei, James R. Sowers
Journal: Circulation Research (2008)

Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the pathogenesis of the cardiometabolic syndrome and cardiovascular disease. Glucose and lipid metabolism are largely dependent on mitochondria to generate energy in cells. Thereby, when nutrient oxidation is inefficient, the ratio of ATP production/oxygen consumption is low, leading to an increased production of superoxide anions. Reactive oxygen species formation may have maladaptive consequences that increase the rate of mutagenesis and stimulate proinflammatory processes. In addition to reactive oxygen species formation, genetic factors, aging, and reduced mitochondrial biogenesis all contribute to mitochondrial dysfunction. These factors also contribute to insulin resistance in classic and nonclassic insulin target tissues. Insulin resistance emanating from mitochondrial dysfunction may contribute to metabolic and cardiovascular abnormalities and subsequent increases in cardiovascular disease. Furthermore, interventions that improve mitochondrial function also improve insulin resistance. Collectively, these observations suggest that mitochondrial dysfunction may be a central cause of insulin resistance and associated complications. In this review, we discuss mechanisms of mitochondrial dysfunction related to the pathophysiology of insulin resistance in classic insulin-responsive tissue, as well as cardiovascular tissue.
Effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring
Authors: K. K. Y. Sie, A. Medline, J. van Weel, K.-J. Sohn, S.-W. Choi, R. Croxford, Y.-I. Kim
Journal: Gut (2011)

<h3>Background</h3> Intrauterine and early life exposure to folic acid has significantly increased in North America owing to folic acid fortification, widespread supplemental use and periconceptional folic acid supplementation. The effect of maternal and postweaning folic acid supplementation on colorectal cancer risk in the offspring was investigated. <h3>Methods</h3> Female rats were placed on a control or supplemental (2.5× the control) diet prior to mating and during pregnancy and lactation. At weaning, male pups from each maternal diet group were randomised to the control or supplemental diet (n=55 per each of the four maternal/pup diet groups) for 31 weeks and colorectal cancer was induced by azoxymethane at 5 weeks of age. At necropsy, colorectal cancer parameters as well as colorectal epithelial proliferation, apoptosis and global DNA methylation were determined in the offspring. <h3>Results</h3> Maternal, but not postweaning, folic acid supplementation significantly reduced the odds of colorectal adenocarcinoma by 64% in the offspring (OR 0.36; 95% CI 0.18 to 0.71; p=0.003). Pups from the dams fed the control diet that were given postweaning folic acid supplementation had significantly higher tumour multiplicity and burden than other groups (p&lt;0.05). Maternal and postweaning folic acid supplementation interacted in a manner that decreased rectal epithelial proliferation (p&lt;0.05). Both maternal and postweaning folic acid supplementation significantly decreased DNA damage in the rectum (p&lt;0.05). Maternal folic acid supplementation significantly increased (p=0.007), whereas postweaning supplementation significantly decreased (p&lt;0.001), colorectal global DNA methylation. <h3>Conclusions</h3> The data suggest for the first time that maternal folic acid supplementation at the level equivalent to the average postfortification total folate intake in North America and to that recommended to women at reproductive age protects against the development of colorectal cancer in the offspring. This protective effect may be mediated in part by increased global DNA methylation and decreased epithelial proliferation and DNA damage in the colorectum.
Balancing Structure and Function at Hippocampal Dendritic Spines
Authors: Jennifer N Bourne, Kristen M Harris
Journal: Annual Review of Neuroscience (2008)

Dendritic spines are the primary recipients of excitatory input in the central nervous system. They provide biochemical compartments that locally control the signaling mechanisms at individual synapses. Hippocampal spines show structural plasticity as the basis for the physiological changes in synaptic efficacy that underlie learning and memory. Spine structure is regulated by molecular mechanisms that are fine-tuned and adjusted according to developmental age, level and direction of synaptic activity, specific brain region, and exact behavioral or experimental conditions. Reciprocal changes between the structure and function of spines impact both local and global integration of signals within dendrites. Advances in imaging and computing technologies may provide the resources needed to reconstruct entire neural circuits. Key to this endeavor is having sufficient resolution to determine the extrinsic factors (such as perisynaptic astroglia) and the intrinsic factors (such as core subcellular organelles) that are required to build and maintain synapses.
Inhibition of VEGF blocks TGF-β<sub>1</sub>production through a PI3K/Akt signalling pathway
Authors: K. S. Lee, S. J. Park, S. R. Kim, K. H. Min, K. Y. Lee, Y. H. Choe, S. H. Hong, Y. R. Lee, J. S. Kim, S. J. Hong, Y. C. Lee
Journal: European Respiratory Journal (2007)

Vascular endothelial growth factor (VEGF) is a mediator of airway inflammation and remodelling in asthma. Transforming growth factor (TGF)-β 1 plays pivotal roles in diverse biological processes, including tissue remodelling and repair in a number of chronic lung diseases. However, there are few studies elucidating the interactions between VEGF and TGF-β 1 in allergic airway disease. A murine model of allergic airway disease was used to define the mechanism by which VEGF induces subepithelial fibrosis and to investigate a potential relationship between VEGF and TGF-β 1 and the mechanisms by which VEGF signalling regulates TGF-β 1 expression in allergic airway disease. The ovalbumin (OVA)-inhaled murine model revealed the following typical pathophysiological features of allergic airway disease in the lungs: increased numbers of inflammatory cells of the airways, airway hyperresponsiveness, increased peribronchial fibrosis, and increased levels of VEGF and TGF-β 1 . Administration of VEGF inhibitors reduced the pathophysiological signs of allergic airway disease and decreased the increased TGF-β 1 levels and peribronchial fibrosis, including phosphoinositide 3-kinase (PI3K) activity after OVA inhalation. In addition, the increased TGF-β 1 levels and collagen deposition after OVA inhalation were decreased by administration of PI3K inhibitors. These results suggest that inhibition of vascular endothelial growth factor attenuates peribronchial fibrosis, at least when mediated by regulation of transforming growth factor-β 1 expression through phosphoinositide 3-kinase/Akt pathway in a murine model of allergic airway disease.
RAGE Blockade Stabilizes Established Atherosclerosis in Diabetic Apolipoprotein E–Null Mice
Authors: Loredana G. Bucciarelli, Thoralf Wendt, Wu Qu, Yan Lu, Evanthia Lalla, Ling Ling Rong, Mouza T. Goova, Bernhard Moser, Thomas Kislinger, Daniel C. Lee, Yogita Kashyap, David M. Stern, Ann Marie Schmidt
Journal: Circulation (2002)

Previous studies suggested that blockade of RAGE in diabetic apolipoprotein (apo) E-null mice suppressed early acceleration of atherosclerosis. A critical test of the potential applicability of RAGE blockade to clinical settings was its ability to impact established vascular disease. In this study, we tested the hypothesis that RAGE contributed to lesion progression in established atherosclerosis in diabetic apoE-null mice.Male apoE-null mice, age 6 weeks, were rendered diabetic with streptozotocin or treated with citrate buffer. At age 14 weeks, certain mice were killed or treated with once-daily murine soluble RAGE or albumin; all mice were killed at age 20 weeks. Compared with diabetic mice at age 14 weeks, albumin-treated animals displayed increased atherosclerotic lesion area and complexity. In diabetic mice treated with sRAGE from age 14 to 20 weeks, lesion area and complexity were significantly reduced and not statistically different from those observed in diabetic mice at age 14 weeks. In parallel, decreased parameters of inflammation and mononuclear phagocyte and smooth muscle cell activation were observed.RAGE contributes not only to accelerated lesion formation in diabetic apoE-null mice but also to lesion progression. Blockade of RAGE may be a novel strategy to stabilize atherosclerosis and vascular inflammation in established diabetes.
Approaching the Therapeutic Window for Cyclosporine in Kidney Transplantation
Authors: Kamran Mahalati, Philip Belitsky, Kenneth West, Bryce Kiberd, Albert Fraser, Ingrid Sketris, Alan S. Macdonald, Vivian Mcalister, Joseph Lawen
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Neoral dosing is traditionally based on cyclosporine (CyA) trough levels (C 0 ). Four-h area under the curve (AUC 0-4 ) for Neoral in the early posttransplantation period was shown previously to have a better correlation to acute rejection (AR) and CyA nephrotoxicity (CyANT), compared with C 0 . An AUC 0-4 range of 4400 to 5500 μg/h per L during the first week was associated with the lowest AR and CyANT. This article describes a prospective study to assess the feasibility, safety, and efficacy of dosing Neoral solely by AUC 0-4 monitoring, regardless of C 0 , in the first 3 mo after kidney transplantation. Fifty-nine kidney transplant recipients received Neoral-based triple immunosuppression. AUC 0-4 was measured on days 3, 5, 7, 10, and 14 and weeks 3, 4, 6, and 8, then monthly. Target AUC 0-4 was 4400 to 5500 μg/h per L. Dose was adjusted by percentage difference from target AUC 0-4 . Ninety-four percent of AUC were performed on the scheduled day or close to it. No patients had CyANT while AUC 0-4 was in target range. Four patients had reversible CyANT with AUC 0-4 &gt; 5500. Only 1 of 33 patients (3%) who achieved and maintained AUC 0-4 &gt; 4400 by day 3 posttransplantation had AR, whereas 10 of 22 (45%) of those with day 3 to 5 AUC 0-4 &lt; 4400 had AR ( P = 0.0002). In logistic regression analysis, higher early AUC 0-4 was the only significant variable associated with lower serum creatinine at 3 mo. Neoral dose monitoring by AUC 0-4 is a potentially valuable tool for optimizing Neoral immunosuppression. Attainment of a target range of 4400 to 5500 μg/h per L for AUC 0-4 early after transplantation has been demonstrated to reduce significantly the risk of AR and CyANT.
Oxford Handbook of Accident and Emergency Medicine
Authors: D W Hamer
Journal: Journal of the Royal Society of Medicine (2005)

The second edition of this very popular handbook follows the layout of the first, with concise and up-to-date information on all aspects of emergency care. References have been added to websites (and articles) and the appearance of the flow charts and diagrams has been improved. Inside the front cover the authors now offer some 'golden rules' for practitioners of emergency medicine and the back cover contains two useful items— an acid-base nomogram and an ECG ruler. This handbook is the best short text for junior doctors practising emergency medicine in the UK and I would like to see it issued to all senior house officers beginning work in the specialty. It will also be useful to medical students or paramedics wanting to know more about emergency treatments.
THE FREQUENCY, ETIOLOGY AND OUTCOME OF ST-ELEVATION MYOCARDIAL INFARCTION PATIENTS REQUIRING URGENT CORONARY ARTERY BYPASS GRAFT
Authors: Craig Tschautscher, David M. Larson, Timothy D. Henry, Jason T. Henry, Monique G. Ross, Robert S. Schwartz, Scott W. Sharkey, Timothy J. Kroshus
Journal: Journal of the American College of Cardiology (2010)
Treatment of Gonorrhoea, Balanitis, and Acquired Phimosis
Authors: T. R. L. Jones
Journal: BMJ (1942)

The agglutinogen present in the plasma of group A recipients is not an absolute protection against anti-A agglutinins.The iso-agglutinin content of serum and plasma pools pre- pared by the techniques used at the London Blood Supply Depots can safely be ignored.[The authors are indebted to Medical Superintendents and staffs of hospitals in Sectors 8 and 9 for access to cases.]
Alloreaction increases or restores CD40, CD54, and/or HLA molecule expression in acute myelogenous leukemia blasts, through secretion of inflammatory cytokines: dominant role for TNFβ, in concert with IFNγ
Authors: A Eljaafari, J Van Snick, A Voisin, F Cormont, A Farre, J Bienvenu, J Bernaud, D Rigal, X Thomas
Journal: Leukemia (2006)
Cyclic 3′,5′-adenosine monophosphate in the human leukocyte: synthesis, degradation, and effects on neutrophil candidacidal activity
Authors: Henry R. Bourne, Robert I. Lehrer, Martin J. Cline, Kenneth L. Melmon
Journal: Journal of Clinical Investigation (1971)

Prostaglandins E(1) and E(2) (PGE(1) and PGE(2)) stimulate adenyl cyclase activity in broken cell preparations of normal human leukocytes, whereas prostaglandin F(1a) produces no effect. PGE(1) and PGE(2) also cause increased accumulation of cyclic 3',5'-adenosine monophosphate-(3)H ((3)H-labeled AMP) in intact leukocytes which have been preincubated with adenine-(3)H in vitro. Theophylline inhibits leukocyte phosphodiesterase activity and potentiates the stimulatory effect of the prostaglandins on intracellular accumulation of cyclic 3',5'-AMP-(3)H. The ability of human granulocytes in vitro to kill Candida albicans was consistently inhibited by PGE(1) and theophylline. This effect was reproduced by dibutyryl cyclic 3',5'-AMP, a lipid-soluble analogue of the endogenous nucleotide. The inhibition of candidacidal activity could not be accounted for by drug effects on phagocytosis, oxygen consumption, or hexose monophosphate shunt activity. These results are consistent with the hypothesis that increased intracellular concentrations of cyclic 3',5'-AMP impair the granulocyte's ability to kill C. albicans, but the precise mechanism of inhibition has not yet been defined.
Phase II Study of Pemetrexed Plus Carboplatin in Malignant Pleural Mesothelioma
Authors: Giovanni L. Ceresoli, Paolo A. Zucali, Adolfo G. Favaretto, Francesco Grossi, Paolo Bidoli, Guido Del Conte, Anna Ceribelli, Alessandra Bearz, Emanuela Morenghi, Raffaele Cavina, Maurizio Marangolo, Hector J. Soto Parra, Armando Santoro
Journal: Journal of Clinical Oncology (2006)

Purpose This multicenter, phase II clinical study was conducted to evaluate the activity of the combination of pemetrexed and carboplatin in patients with malignant pleural mesothelioma (MPM). Patients and Methods Chemotherapy-naive patients with measurable disease and adequate organ function, who were not eligible for curative surgery, received pemetrexed 500 mg/m 2 and carboplatin area under the plasma concentration-time curve of 5 mg/mL/min, administered intravenously every 21 days. All patients received folic acid and vitamin B 12 supplementation. Pemetrexed was provided within the Expanded Access Program. Results A total of 102 patients were enrolled. An objective response was achieved in 19 patients (two complete and 17 partial responses), for a response rate of 18.6% (95% CI, 11.6% to 27.5%). Forty-eight patients (47.0%; 95% CI, 37.1% to 57.2%) had stable disease after treatment. Overall, 67 patients (65.7%) achieved disease control (95% CI, 55.6% to 74.8%). Median time to progression was 6.5 months; median overall survival time was 12.7 months. Compliance to treatment was excellent, with a relative dose-intensity of 97% for pemetrexed and 98% for carboplatin. Toxicity was mild, with grade 3 or 4 neutropenia occurring in 9.7% of total cycles and grade 3 or 4 anemia occurring in 3.5% of total cycles. Nonhematologic toxicity was negligible. Conclusion Treatment with pemetrexed and carboplatin was active and well tolerated in patients with MPM. Disease control rate, time to disease progression, and overall survival were similar to the results achieved with the standard regimen of pemetrexed and cisplatin, suggesting that the carboplatin combination could be an alternative option for these patients.