tbuckley/cabot-search huggingface dataset:
Frequency of beryllium-specific, central memory CD4+ T cells in blood determines proliferative response
Authors: A. P. Fontenot
Journal: Journal of Clinical Investigation (2005)

Beryllium exposure can lead to the development of beryllium-specific CD4+ T cells and chronic beryllium disease (CBD), which is characterized by the presence of lung granulomas and a CD4+ T cell alveolitis. Studies have documented the presence of proliferating and cytokine-secreting CD4+ T cells in blood of CBD patients after beryllium stimulation. However, some patients were noted to have cytokine-secreting CD4 T cells in blood in the absence of beryllium-induced proliferation, and overall, the correlation between the 2 types of responses was poor. We hypothesized that the relative proportion of memory T cell subsets determined antigen-specific proliferation. In most CBD patients, the majority of beryllium-specific CD4+ T cells in blood expressed an effector memory T cell maturation phenotype. However, the ability of blood cells to proliferate in the presence of beryllium strongly correlated with the fraction expressing a central memory T cell phenotype. In addition, we found a direct correlation between the percentage of beryllium-specific CD4+ T(EM) cells in blood and T cell lymphocytosis in the lung. Together, these findings indicate that the functional capability of antigen-specific CD4+ T cells is determined by the relative proportion of memory T cell subsets, which may reflect internal organ involvement.
Chemotherapy in Advanced Gastric Cancer: A Systematic Review and Meta-Analysis Based on Aggregate Data
Authors: Anna D. Wagner, Wilfried Grothe, Johannes Haerting, Gerhard Kleber, Axel Grothey, Wolfgang E. Fleig
Journal: Journal of Clinical Oncology (2006)

Purpose This systematic review and meta-analysis were performed to assess the efficacy and tolerability of chemotherapy in patients with advanced gastric cancer. Methods Randomized phase II and III clinical trials on first-line chemotherapy in advanced gastric cancer were identified by electronic searches of Medline, Embase, the Cochrane Controlled Trials Register, and Cancerlit; hand searches of relevant abstract books and reference lists; and contact to experts. Meta-analysis was performed using the fixed-effect model. Overall survival, reported as hazard ratio (HR) with 95% CI, was the primary outcome measure. Results Analysis of chemotherapy versus best supportive care (HR = 0.39; 95% CI, 0.28 to 0.52) and combination versus single agent, mainly fluorouracil (FU) -based chemotherapy (HR = 0.83; 95% CI = 0.74 to 0.93) showed significant overall survival benefits in favor of chemotherapy and combination chemotherapy, respectively. In addition, comparisons of FU/cisplatin-containing regimens with versus without anthracyclines (HR = 0.77; 95% CI, 0.62 to 0.95) and FU/anthracycline-containing combinations with versus without cisplatin (HR = 0.83; 95% CI, 0.76 to 0.91) both demonstrated a significant survival benefit for the three-drug combination. Comparing irinotecan-containing versus nonirinotecan-containing combinations (mainly FU/cisplatin) resulted in a nonsignificant survival benefit in favor of the irinotecan-containing regimens (HR = 0.88; 95% CI, 0.73 to 1.06), but they have never been compared against a three-drug combination. Conclusion Best survival results are achieved with three-drug regimens containing FU, an anthracycline, and cisplatin. Among these, regimens including FU as bolus exhibit a higher rate of toxic deaths than regimens using a continuous infusion of FU, such as epirubicin, cisplatin, and continuous-infusion FU.
Efficacy of sustained release theophylline given at three different evening intake times in addition to a baseline medication
Authors: B Siebert, G Kunkel, K Borner, HW Staudinger, VW Steinijans
Journal: European Respiratory Journal (1990)

In this randomized crossover study of 26 outpatients with bronchial asthma the efficacy of a new once-daily theophylline formulation given in addition to a baseline medication was investigated; moreover, under steady state conditions, the effect of three evening intake times (6, 8 and 10 p.m.) on 24 h pharmacokinetics and peak-expiratory flow profiles was evaluated. The theophylline dose had been individually titrated. The pharmacodynamic results show a marked improvement of 24 h peak expiratory flow values after adding theophylline to a drug therapy including inhalative beta 2-agonists and corticosteroids in nearly all and inhalative anticholinergics in 50% of the treated outpatients. No significant differences between the pharmacokinetic characteristics and the 24 hr averages (mesors) of peak expiratory flow at the three different intake times 6, 8 and 10 p.m. were found; however, intake at 10 p.m. resulted in the highest nocturnal excess of serum theophylline concentrations and the highest peak expiratory flow during the early morning hours between 2 and 6 a.m.
Fever, splenomegaly and lymphopenia in sarcoidosis
Authors: Claudia Ravaglia, Carlo Gurioli, Gian Luca Casoni, Silvia Asioli, Venerino Poletti
Journal: Thorax (2012)

A 42-year-old woman was referred to our department with a 5 months history of intermittent fever and fatigue. Her past medical history included a consolidated diagnosis of sarcoidosis (obtained 7 years before with a sub-carinal lymph node biopsy) and in the previous years she had been treated with steroids, hydroxychloroquine, methotrexate and azathioprine with persistent and progressive enlargement of mediastino-hilar adenopathies and bilateral nodular infiltrates. Her symptoms progressed despite a course of antibiotics prescribed for presumed community-acquired pneumonia and a course of corticosteroids. The patient lived in Italy and there was no history of travels or other additional risk factors for infections.

At the time of admission, the patient had a temperature of …
Significance of finger clubbing in asbestosis.
Authors: I I Coutts, J C Gilson, I H Kerr, W R Parkes, M Turner-Warwick
Journal: Thorax (1987)

The prognostic significance of finger clubbing in asbestosis has been assessed in 167 cases certified by the London Pneumoconiosis Medical Panel from 1968 to 1974. Finger clubbing developed early in the clinical course of the disease and was associated with a lower gas transfer, a higher mortality and a greater likelihood of progression in intrapulmonary fibrosis than was found among cases without finger clubbing. Finger clubbing was not associated with heavier asbestos exposure. Its presence appears to be associated with a more severe form of disease.
Development and validation of a new method for the registration of overuse injuries in sports injury epidemiology: the Oslo Sports Trauma Research Centre (OSTRC) Overuse Injury Questionnaire
Authors: Benjamin Clarsen, Grethe Myklebust, Roald Bahr
Journal: British Journal of Sports Medicine (2012)

Background Current methods for injury registration in sports injury epidemiology studies may substantially underestimate the true burden of overuse injuries due to a reliance on time-loss injury definitions. Objective To develop and validate a new method for the registration of overuse injuries in sports. Methods A new method, including a new overuse injury questionnaire, was developed and validated in a 13-week prospective study of injuries among 313 athletes from five different sports, cross-country skiing, floorball, handball, road cycling and volleyball. All athletes completed a questionnaire by email each week to register problems in the knee, lower back and shoulder. Standard injury registration methods were also used to record all time-loss injuries that occurred during the study period. Results The new method recorded 419 overuse problems in the knee, lower back and shoulder during the 3-month-study period. Of these, 142 were classified as substantial overuse problems, defined as those leading to moderate or severe reductions in sports performance or participation, or time loss. Each week, an average of 39% of athletes reported having overuse problems and 13% reported having substantial problems. In contrast, standard methods of injury registration registered only 40 overuse injuries located in the same anatomical areas, the majority of which were of minimal or mild severity. Conclusion Standard injury surveillance methods only capture a small percentage of the overuse problems affecting the athletes, largely because few problems led to time loss from training or competition. The new method captured a more complete and nuanced picture of the burden of overuse injuries in this cohort.
Vitamin D Levels and Sensitization To Indoor Inhalant Allergens In Korea
Authors: Kyung-Hwan Lim, Min-Gyu Kang, Han-Ki Park, So-Hee Lee, Min-Suk Yang, Woo-Jung Song, Hye-Ryun Kang, Heung-Woo Park, Sun-Sin Kim, Yoon-Seok Chang, Sang Heon Cho, Kyung-Up Min, Sae-Hoon Kim
Journal: Journal of Allergy and Clinical Immunology (2014)
Treatment with tumour necrosis factor inhibitor oxpentifylline does not improve corticosteroid dependent chronic active Crohn's disease.
Authors: J Bauditz, J Haemling, M Ortner, H Lochs, A Raedler, S Schreiber
Journal: Gut (1997)

BACKGROUND: In Crohn9s disease, inflammation is presumably sustained by an increased production of proinflammatory cytokines, in particular tumour necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL 1 beta). TNF alpha can induce a host of cellular effector events resulting in perpetuation of the inflammatory process. In vivo studies with anti-TNF alpha antibody treatment have led to impressive clinical results. AIMS: To investigate whether treatment with the TNF alpha inhibitor oxpentifylline results in clinical improvement in corticosteroid dependent chronic active Crohn9s disease. METHODS: Sixteen Crohn9s disease patients received oxpentifylline 400 mg four times a day in a four week open label study. RESULTS: Blockade of TNF alpha production in 16 patients with corticosteroid dependent Crohn9s disease did not improve the clinical disease activity (CDAI mean (SEM) 188.75 (5.65) versus 185.13 (10.87) or the endoscopic degree of inflammation (CDEIS 14.9 (2.87) versus 14.8 (2.27) or laboratory parameters. CONCLUSIONS: In this study, use of the TNF alpha inhibitor oxpentifylline does not improve inflammation in Crohn9s disease. This finding suggests that there may be more key mediators than only TNF alpha in the inflammatory process in Crohn9s disease.
Hypoplastic Left Heart Syndrome With Left Ventricular Myocardial Sinusoids: Echocardiographic and Angiographic Findings in the First Neonate Surviving the Norwood I and II Procedure
Authors: Harald Bertram, Marc-Phillip Hitz, Masamichi Ono, Michael Sasse, Armin Wessel, Thomas Breymann, T. Mesud Yelbuz
Journal: Circulation (2008)
High frequency of voriconazole-related phototoxicity in cystic fibrosis patients
Authors: S. Rondeau, L. Couderc, S. Dominique, S. Pramil, C. Leguillon, B. Masseline, L. Favennec, C. Marguet
Journal: European Respiratory Journal (2012)

To the Editors:

Aspergillus fumigatus infection is common in cystic fibrosis (CF) patients and estimates of the rate of allergic bronchopulmonary aspergillosis range from 1–15%. Voriconazole, a new triazole antifungal, has been recognised as efficient and safe in the treatment of invasive aspergillosis [1–2]. Since it is available orally, voriconazole became the first alternative to itraconazole. We began giving voriconazole to CF patients in 2003, and we encountered an unexpectedly high frequency of moderate-to-severe skin reactions, which limited the administration of the drug.

We therefore reviewed all the medical files of children (aged <18 yrs; n=72) and adults (n=63) followed up in our tertiary CF reference centre between April 2003 and December 2008, in order to estimate the frequency of voriconazole-induced photosensitivity, as previously defined [3]. All the patients who were given voraconazole were selected. Demographic data, cystic fibrosis transmembrane conductance regulator (CFTR) mutations, clinical data, treatment, duration and voriconazole dosage, and related adverse effects (AEs) were collected. Qualitative and quantitative comparisons were analysed using the Chi-squared test and nonparametric Mann–Whitney test, respectively. Multivariate analyses were performed by using stepwise logistic regression. A p-value <0.05 was considered statistically significant. Statistical analyses were performed using Statistica 8 (StatSoft, Maisons-Alfort, France).

31 (21.4%) out of the 135 CF patients were given voriconazole. Their characteristics are described in table 1. When genotypes were categorised into CFTR mutation classes, 36.5% and 58%, respectively, were heterozygous and homozygous for class II mutations, which alter the maturation of CFTR protein. Voriconazole-related AEs were reported in 19 (61%) …
Mechanisms of Ploidy Increase in Human Cancers: A New Role for Cell Cannibalism
Authors: Matej Krajcovic, Michael Overholtzer
Journal: Cancer Research (2012)

Abstract Aneuploidy is a hallmark of human cancers originating from abnormal mitoses. Many aneuploid cancer cells also have greater-than-diploid DNA content, suggesting that polyploidy is a common precursor to aneuploidy during tumor progression. Polyploid cells can originate from cell fusion, endoreplication, and cytokinesis failure. Recently we found that cell cannibalism by entosis, a form of cell engulfment involving live cells, also leads to polyploidy, as internalized cells disrupt cytokinesis of their engulfing cell hosts. By this mechanism, cannibalistic cell behavior could promote tumor progression by leading to aneuploidy. Here, we discuss cell cannibalism in cancer and other mechanisms that result in the formation of polyploid cancer cells. Cancer Res; 72(7); 1596–601. ©2012 AACR.
Polarization of Chemokine Receptors to the Leading Edge during Lymphocyte Chemotaxis
Authors: Marta Nieto, José M.R. Frade, David Sancho, Mario Mellado, Carlos Martinez-A, Francisco Sánchez-Madrid
Journal: The Journal of Experimental Medicine (1997)

Leukocyte migration in response to cell attractant gradients or chemotaxis is a key phenomenon both in cell movement and in the inflammatory response. Chemokines are quite likely to be the key molecules directing migration of leukocytes that involve cell polarization with generation of specialized cell compartments. The precise mechanism of leukocyte chemoattraction is not known, however. In this study, we demonstrate that the CC chemokine receptors CCR2 and CCR5, but not cytokine receptors such as interleukin (IL)-2Ralpha, IL-2Rbeta, tumor necrosis factor receptor 1, or transforming growth factor betaR, are redistributed to a pole in T cells that are migrating in response to chemokines. Immunofluorescence and confocal microscopy studies show that the chemokine receptors concentrate at the leading edge of the cell on the flattened cell-substratum contact area, induced specifically by the signals that trigger cell polarization. The redistribution of chemokine receptors is blocked by pertussis toxin and is dependent on cell adhesion through integrin receptors, which mediate cell migration. Chemokine receptor expression on the leading edge of migrating polarized lymphocytes appears to act as a sensor mechanism for the directed migration of leukocytes through a chemoattractant gradient.
The Pharmacology of Regenerative Medicine
Authors: George J. Christ, Justin M. Saul, Mark E. Furth, Karl-Erik Andersson
Journal: Pharmacological Reviews (2013)

Regenerative medicine is a rapidly evolving multidisciplinary, translational research enterprise whose explicit purpose is to advance technologies for the repair and replacement of damaged cells, tissues, and organs. Scientific progress in the field has been steady and expectations for its robust clinical application continue to rise. The major thesis of this review is that the pharmacological sciences will contribute critically to the accelerated translational progress and clinical utility of regenerative medicine technologies. In 2007, we coined the phrase "regenerative pharmacology" to describe the enormous possibilities that could occur at the interface between pharmacology, regenerative medicine, and tissue engineering. The operational definition of regenerative pharmacology is "the application of pharmacological sciences to accelerate, optimize, and characterize (either in vitro or in vivo) the development, maturation, and function of bioengineered and regenerating tissues." As such, regenerative pharmacology seeks to cure disease through restoration of tissue/organ function. This strategy is distinct from standard pharmacotherapy, which is often limited to the amelioration of symptoms. Our goal here is to get pharmacologists more involved in this field of research by exposing them to the tools, opportunities, challenges, and interdisciplinary expertise that will be required to ensure awareness and galvanize involvement. To this end, we illustrate ways in which the pharmacological sciences can drive future innovations in regenerative medicine and tissue engineering and thus help to revolutionize the discovery of curative therapeutics. Hopefully, the broad foundational knowledge provided herein will spark sustained conversations among experts in diverse fields of scientific research to the benefit of all.
Differences in Cyclic AMP Changes after Stimulation by Prostaglandins and Isoproterenol in Lymphocyte Subpopulations
Authors: Marie-Anne Bach
Journal: Journal of Clinical Investigation (1975)

Various lymphocyte populations have been studied for their content in cyclic adenosine 3',5'-monophosphate (cAMP) before and after stimulation by isoproterenol and prostaglandin E(1) (PGE(1)). Basal cAMP levels vary among lymphocytes according to their origin: peripheral blood lymphocytes show high cAMP level while spleen and lymph node cells and thymocytes show lower levels. Thymocytes are extremely sensitive to the stimulating effects of isoproterenol and PGE(1), much more than spleen and lymph node or peripheral blood cells. Corticoresistant thymocytes are less sensitive to isoproterenol stimulation than normal thymocytes, but are significantly more sensitive than peripheral thymus-derived (T)-cells. Studies using bone-marrow-derived (B) or T cell depletion with anti-immunoglobulin-coated columns and antitheta serum (AthetaS) indicate that lymph node B cells synthesize more cAMP in the presence of isoproterenol than T cells. However, this difference between T and B cells has not been found in spleen cells.
Insulin Resistance in Liver Cirrhosis Is Not Associated With Circulating Retinol-Binding Protein 4
Authors: Eray Yagmur, Ralf Weiskirchen, Axel M. Gressner, Christian Trautwein, Frank Tacke
Journal: Diabetes Care (2007)

OBJECTIVE—Retinol-binding protein 4 (RBP4) has been identified as a novel adipokine mediating systemic insulin resistance, and elevated serum RBP4 indicates overt or impending insulin resistance in lean, obese, and type 2 diabetic subjects. As insulin resistance is present in nearly all patients with liver cirrhosis, we evaluated RBP4 in patients with chronic liver disease (CLD). RESEARCH DESIGN AND METHODS—Serum RBP4 was measured in 111 CLD patients. Ninety-nine age- and sex-matched healthy blood donors served as control subjects. RBP4 gene expression was also quantified in normal and cirrhotic rat liver. RESULTS—In CLD patients, serum RBP4 was significantly reduced compared with healthy control subjects and closely correlated with the stage of liver cirrhosis. CLD patients without cirrhosis showed normal RBP4 concentrations, which correlated with serum glucose and insulin secretion and inversely correlated with insulin sensitivity. In patients with Child A-C liver cirrhosis, however, RBP4 was not correlated with glucose metabolism or other adipokines, such as adiponectin or resistin, but closely linked to the hepatic biosynthetic capacity, fibrotic changes in liver histology, or clinical complications such as portal hypertension. In an animal model of experimental cirrhosis, hepatic RBP4 gene expression decreased in cirrhotic liver. CONCLUSIONS—RBP4 appears, unlike in obesity or type 2 diabetes, not to be a relevant systemic factor in the pathogenesis of insulin resistance in liver cirrhosis. Liver function has a tremendous impact on RBP4 levels, and future studies will need to take liver function into account when examining serum RBP4 levels.
THE USE OF PHOSPHORUS 32 IN STUDIES ON PLASMODIUM GALLINACEUM
Authors: Delphine H. Clarke
Journal: The Journal of Experimental Medicine (1952)

A quantitative method for following parasite growth in vitro is described. The method is based on the determination of the degree of incorporation of phosphorus into the nucleic acids, in particular desoxypentose nucleic acids, of the parasitized cell. Phosphorus incorporation is measured by utilizing the radioactive isotope, P(32). The degree of phosphorus incorporation into DNA was found to be closely correlated with estimates of parasite growth based on stained film examinations of intact cell preparations. The isotope was likewise found to be incorporated into the DNA of preparations in which the host cell had been disrupted by lysis and the extent of this incorporation also paralleled the impressions gained from smear examinations. It is suggested that this method provides a sensitive and objective method of studying parasite growth.
Less than a third of Scottish hospitals meet targets on giving thrombolysis
Authors: Bryan Christie
Journal: BMJ (2001)

The first performance report on Scottish hospitals has found high levels of compliance with standards on treating heart attacks but has uncovered failings in the administration of thrombolysis.

The report from the Clinical Standards Board for Scotland found that only 10 out of 37 hospitals met the standard for administering thrombolysis to 50% of patients within 30 minutes of admission to hospital with a heart attack. It recommends that hospitals failing to meet the standard should review their admission arrangements to ensure that speedier treatment can be given.

The report …
Low Serum Insulin-Like Growth Factor I Is Associated With Increased Risk of Ischemic Heart Disease
Authors: Anders Juul, Thomas Scheike, Michael Davidsen, Jesper Gyllenborg, Torben Jørgensen
Journal: Circulation (2002)

Background— Insulin-like growth factor I (IGF-I) has been suggested to be involved in the pathogenesis of atherosclerosis. We hypothesize that low IGF-I and high IGFBP-3 levels might be associated with increased risk of ischemic heart disease (IHD). Methods and Results— We conducted a nested case-control study within a large prospective study on cardiovascular epidemiology (DAN-MONICA). We measured IGF-I and IGFBP-3 in serum from 231 individuals who had a diagnosis of IHD 7.63 years after blood sampling and among 374 control subjects matched for age, sex, and calendar time. At baseline when all individuals were free of disease, subjects in the low IGF-I quartile had significantly higher risk of IHD during the 15-year follow-up period, with a relative risk (RR) of 1.94 (95% CI, 1.03 to 3.66) of IHD compared with the high IGF-I quartile group, when IGFBP-3, body mass index, smoking, menopause, diabetes, and use of antihypertensives were controlled for. Conversely, individuals in the high IGFBP-3 quartile group had an adjusted RR of 2.16 (95% CI, 1.18 to 3.95) of having IHD. Identification of a high-risk population with low IGF-I and high IGFBP-3 levels resulted in markedly higher risk of IHD (RR 4.07; 95% CI, 1.48 to 11.22) compared with the index group. Conclusions— Individuals without IHD but with low circulating IGF-I levels and high IGFBP-3 levels have significantly increased risk of developing IHD during a 15-year follow-up period. Our findings suggest that IGF-I may be involved in the pathogenesis of IHD.
The effect of steroids and ammonium chloride acidosis on phosphoenolpyruvate carboxykinase in rat kidney cortex
Authors: I. D. Longshaw, G. A. O. Alleyne, C. I. Pogson
Journal: Journal of Clinical Investigation (1972)

The kinetics of the induction of rat kidney phosphoenolpyruvate carboxykinase activity after triamcinolone and ammonium chloride administration have been investigated with a view to the further differentiation of the two processes.