tbuckley/cabot-search huggingface dataset:
Superoxide anions produced by inflammatory cells play an important part in the pathogenesis of acid and pepsin induced oesophagitis in rabbits.
Authors: M J Naya, D Pereboom, J Ortego, J O Alda, A Lanas
Journal: Gut (1997)

BACKGROUND: Reactive oxygen metabolites have been associated with gastrointestinal injury. OBJECTIVE: To investigate whether mucosal reactive oxygen metabolites are involved in acid and pepsin induced oesophagitis, and if so, which specific metabolites. METHODS: The effects of free radical scavengers and the anti-inflammatory drug ketotifen on rabbit oesophagitis induced by acidified pepsin were studied. Isolated oesophageal cells were obtained before and after oesophageal injury and the generation of superoxide anion and hydrogen peroxide was analysed by flow cytometry. The presence of inflammatory cells was determined by indirect immunofluorescence with a mouse antirabbit CD11b antibody. RESULTS: Of the free radical scavengers tested, superoxide dismutase, which reacts with the superoxide anion, significantly reduced oesophagitis, whereas catalase, which reacts with hydrogen peroxide, had only a mild effect and dimethylsulphoxide had no effect. Ketotifen significantly reduced the inflammation and also prevented the induction of oesophagitis. Isolated cells obtained from the oesophageal mucosa after acidified pepsin exposure generated increased amounts of superoxide anions, which were mainly produced by CD11b positive cells. CONCLUSIONS: Reactive oxygen metabolites, especially superoxide anion, produced by inflammatory cells play a significant part in the genesis of oesophagitis induced by acid and pepsin in rabbits and might be a target for future medical therapy.
P250 Mycoplasma pneumonia. Presenting features and diagnosis in our district general hospital in 2010
Authors: K. S. Caldwell, R. Johns, L. Teare, H. S. Jenkins
Journal: Thorax (2011)

<h3>Introduction</h3> <i>Mycoplasma pneumoniae</i> is a common cause of pneumonia. Incidence ranges from 0.5 to 5.0 per 1000 population or up to 20% of all pneumonias, and generally declines with age, being rare in adults over 50. Classically epidemics occur in 4 to 7-year cycles. Usual features are insidious onset “viral”-type symptoms, including fever, headache, dyspnoea and dry cough, together with a variety of extra pulmonary manifestations. Diagnosis is often missed because of the atypical and unusual presentation. <h3>Methods and Results</h3> We examined electronic records of patients during 2010 diagnosed with <i>M pneumoniae</i> by an elevated specific IgM immunoassay method. There were 35 cases. Of those, 20 required acute admission to our hospital (18 adults and two children). In adults, common presenting features were fever, cough, headaches, lethargy and myalgia. Major presenting features, however, were meningitis/encephalitis in two patients, Stevens-Johnson syndrome in 1, confusion in 1, and haemoptysis in 1. In six adults (33%), the diagnosis was not made during hospital admission, and symptoms were erroneously attributed to presumptive diagnoses of viral meningitis, acute viral illness, dyspnoea of unknown cause, asthma/pericarditis, and an acute drug reaction. We compared length of admission in patients diagnosed early on in admission to those misdiagnosed or diagnosed late; early diagnosis of <i>M pneumoniae</i> using this method was associated with significantly shorter lengths of stay. <h3>Conclusion and Discussion</h3> An appreciation of common presenting clinical features of <i>Mycoplasma</i> is important in ensuring the diagnosis is made promptly and not missed. The advantage of an IgM based assay is the detection of early/acute illness rather than convalescent disease (as in the case of parallel assays of acute and convalescent samples), having the potential to change management, refine antibiotics where appropriate and also to potentiate early discharge.
Conserved and Tissue-Specific Genic and Physiologic Responses to Caloric Restriction and Altered IGFI Signaling in Mitotic and Postmitotic Tissues
Authors: Stephen R. Spindler, Joseph M. Dhahbi
Journal: Annual Review of Nutrition (2007)

Caloric restriction (CR), the consumption of fewer calories without malnutrition, and reduced insulin and/or IGFI receptor signaling delay many age-related physiological changes and extend the lifespan of many model organisms. Here, we present and review microarray and biochemical studies indicating that the potent anticancer effects of CR and disrupted insulin/IGFI receptor signaling evolved as a byproduct of the role of many mitotic tissues as reservoirs of metabolic energy. We argue that the longevity effects of CR are derived from repeated cycles of apoptosis and autophagic cell death in mitotically competent tissues and protein turnover and cellular repair in postmitotic tissues. We review studies showing that CR initiated late in life can rapidly induce many of the benefits of lifelong CR, including its anticancer effects. We also discuss evidence from liver and heart indicating that many benefits of lifelong CR are recapitulated in mitotic and postmitotic tissues when CR is initiated late in life.
Effect of ozonation on the removal of cyanobacterial toxins during drinking water treatment.
Authors: Stefan J Hoeger, Daniel R Dietrich, Bettina C Hitzfeld
Journal: Environmental Health Perspectives (2002)

Water treatment plants faced with toxic cyanobacteria have to be able to remove cyanotoxins from raw water. In this study we investigated the efficacy of ozonation coupled with various filtration steps under different cyanobacterial bloom conditions. Cyanobacteria were ozonated in a laboratory-scale batch reactor modeled on a system used by a modern waterworks, with subsequent activated carbon and sand filtration steps. The presence of cyanobacterial toxins (microcystins) was determined using the protein phosphatase inhibition assay. We found that ozone concentrations of at least 1.5 mg/L were required to provide enough oxidation potential to destroy the toxin present in 5 X 10(5 )Microcystis aeruginosa cells/mL [total organic carbon (TOC), 1.56 mg/L]. High raw water TOC was shown to reduce the efficiency of free toxin oxidation and destruction. In addition, ozonation of raw waters containing high cyanobacteria cell densities will result in cell lysis and liberation of intracellular toxins. Thus, we emphasize that only regular and simultaneous monitoring of TOC/dissolved organic carbon and cyanobacterial cell densities, in conjunction with online residual O(3) concentration determination and efficient filtration steps, can ensure the provision of safe drinking water from surface waters contaminated with toxic cyanobacterial blooms.
<i>MDM2</i> SNP309 Is Associated With Poor Outcome in B-Cell Chronic Lymphocytic Leukemia
Authors: Irina Gryshchenko, Sebastian Hofbauer, Markus Stoecher, Peter T. Daniel, Michael Steurer, Alexander Gaiger, Karin Eigenberger, Richard Greil, Inge Tinhofer
Journal: Journal of Clinical Oncology (2008)

Purpose A single nucleotide polymorphism (SNP) at position 309 in the promoter region of MDM2 leading to increased expression of MDM2 and attenuated function of p53 has been negatively associated with onset and outcome of disease in solid tumors. Because inactivation of p53 by deletion and/or mutations also impacts on the clinical course of B-cell chronic lymphocytic leukemia (B-CLL), we assessed the role of the SNP309 genotype in B-CLL. Patients and Methods The frequency of SNP309 T/T, T/G, or G/G genotypes and the p53 status (wild type, mutated, or deleted) were assessed and correlated with clinical outcome in 140 B-CLL patients and a second independent cohort. In addition, the correlation of the MDM2 SNP309 genotype with the MDM2 protein expression level in B-CLL cells was evaluated by immunoblotting. Results A significant negative association of the SNP309 T/G and G/G genotypes with overall survival was seen (T/G genotype, relative risk = 3.7; 95% CI, 1.2 to 11.5; P = .02; G/G genotype, relative risk = 9.1; 95% CI, 2.4 to 35.1; P = .001), but no correlation with incidence or onset of B-CLL was observed. The influence of the heterozygous SNP309 T/G genotype on treatment-free survival depended on the p53 status but not on the CD38, Zap-70, or IgVH mutational status or Rai stage of B-CLL patients. The unfavorable SNP309 T/G and G/G genotypes were associated with a gene-dosage–dependent increase of MDM2 expression. Conclusion The MDM2 SNP309 genotype influencing MDM2 expression levels was identified as an additional independent risk factor in B-CLL. Targeting MDM2-p53 interactions might emerge as a successful treatment strategy for B-CLL.
Patrick ("Paddy") Francis Ahern William Maurice Ankers Arthur Eliot Barr Hugh Kenneth Childs Harry Lloyd Fairbridge Currey James Matheson Fleming Elizabeth Rothwell ("Liz") Germany George Lees Gibson John Ludovic ("Jack") Grant Andrew Grierson Brian Edyvean Heard Nicholas Barrick Ingledew Hamid Ali Khan Elizabeth ("Lizzie") Mary Lenman Alexander Macdonald Henry Martyn ("Harry") McGladdery John Miller Hunter Mitchell Mohammad Nadeem Hugh Noel O'Donoghue David Lewis Parry Richard Edgar Alfred ("…
Authors: J. Treleaven, J. Danks, G. Brill, H. Rooke, A. Resouly, J. A Mathews, R. Fleming, E. R Germany, R N Peel, J. Fletcher, M E Blacklee, B. Corrin, N. Tai, W. Mitchell, N. M Quadri, C. Robertshaw, W. Jaffe, K B Fraser, J A McGladdery, A P Davidson, J Berth-Jones, A Ilchyshyn, M. O'Riordan, M. Mackrill, R. W H Price
Journal: BMJ (1998)
Continuing insights into the heart as an endocrine organ: adrenomedullin and cardiac fibroblasts
Authors: M Jougasaki
Journal: Cardiovascular Research (2001)

See article by Tomoda et al. [15] (pages 721–730) in this issue. 

In 1993, Kitamura et al. [1] discovered a novel hypotensive peptide in human pheochromocytoma by means of monitoring the ability of extracted fractions to increase platelet cyclic adenosine 3′,5′-monophosphate (cAMP), which they named adrenomedullin. Human adrenomedullin consists of 52 amino acids and has an intramolecular disulfide bond and C-terminal amide structure, which shows 27% homology with calcitonin gene related peptide (CGRP), suggesting that adrenomedullin belongs to the CGRP superfamily. Adrenomedullin immunoreactivity and its gene expression are widely distributed in cardiovascular, pulmonary, renal, gastrointestinal, cerebral and endocrine tissues. Studies have demonstrated that adrenomedullin elicits a hypotensive effect through at least two mechanisms, a direct action on vascular smooth muscle cells, to increase intracellular cAMP, and an action on endothelial cells, to stimulate nitric oxide release, both of which lead to vascular relaxation [2]. When adrenomedullin is injected intravenously, it increases flow rates predominantly in organs in which the adrenomedullin gene is highly expressed, suggesting that adrenomedullin acts as a local autocrine and/or paracrine vasoactive hormone … 

* Corresponding author. Tel.: +1-507-284-4838; fax: +1-507-266-4710 jougasaki{at}mayo.edu
Stromal Cell–Derived Factor-1 Effects on Ex Vivo Expanded Endothelial Progenitor Cell Recruitment for Ischemic Neovascularization
Authors: Jun-ichi Yamaguchi, Kengo Fukushima Kusano, Osamu Masuo, Atsuhiko Kawamoto, Marcy Silver, Satoshi Murasawa, Marta Bosch-Marce, Haruchika Masuda, Douglas W. Losordo, Jeffrey M. Isner, Takayuki Asahara
Journal: Circulation (2003)

Stromal cell-derived factor-1 (SDF-1) is a chemokine considered to play an important role in the trafficking of hematopoietic stem cells. Given the close relationship between hematopoietic stem cells and endothelial progenitor cells (EPCs), we investigated the effect of SDF-1 on EPC-mediated vasculogenesis.Flow cytometric analysis demonstrated expression of CXCR4, the receptor of SDF-1, by 66+/-3% of EPCs after 7 days in culture. In vitro modified Boyden chamber assay showed a dose-dependent EPC migration toward SDF-1 (control versus 10 ng/mL SDF-1 versus 100 ng/mL SDF-1, 24+/-2 versus 71+/-3 versus 140+/-6 cells/mm2; P<0.0001). SDF-1 attenuated EPC apoptosis (control versus SDF-1, 27+/-1 versus 7+/-1%; P<0.0001). To investigate the effect of SDF-1 in vivo, we locally injected SDF-1 into athymic ischemic hindlimb muscle of nude mice combined with human EPC transplantation to determine whether SDF-1 augmented EPC-induced vasculogenesis. Fluorescence microscopic examination disclosed increased local accumulation of fluorescence-labeled EPCs in ischemic muscle in the SDF-1 treatment group (control versus SDF-1=241+/-25 versus 445+/-24 cells/mm2, P<0.0001). At day 28 after treatment, ischemic tissue perfusion was improved in the SDF-1 group and capillary density was also increased. (control versus SDF-1, 355+/-26 versus 551+/-30 cells/mm2; P<0.0001).These findings indicate that locally delivered SDF-1 augments vasculogenesis and subsequently contributes to ischemic neovascularization in vivo by augmenting EPC recruitment in ischemic tissues.
Antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease: a cost effectiveness analysis
Authors: P Krijnen
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To assess the cost effectiveness of antibiotic prophylaxis for haematogenous bacterial arthritis in patients with joint disease. <h3>METHODS</h3> In a decision analysis, data from a prospective study on bacterial arthritis in 4907 patients with joint disease were combined with literature data to assess risks and benefits of antibiotic prophylaxis. Effectiveness and cost effectiveness calculations were performed on antibiotic prophylaxis for various patient groups. Grouping was based on (<i>a</i>) type of event leading to transient bacteraemia—that is, infections (dermal, respiratory/urinary tract) and invasive medical procedures—and (<i>b</i>) the patient9s susceptibility to bacterial arthritis which was increased in the presence of rheumatoid arthritis, large joint prostheses, comorbidity, and old age. <h3>RESULTS</h3> Of the patients with joint disease, 59% had no characteristics that increased susceptibility to bacterial arthritis, and 31% had one. For dermal infections, the effectiveness of antibiotic prophylaxis was maximally 35 quality adjusted life days (QALDs) and the cost effectiveness maximally $52 000 per quality adjusted life year (QALY). For other infections, the effectiveness of prophylaxis was lower and the cost effectiveness higher. Prophylaxis for invasive medical procedures seemed to be acceptable only in patients with high susceptibility: 1 QALD at a cost of $1300/QALY; however, the results were influenced substantially when the level of efficacy of the prophylaxis or cost of prophylactic antibiotics was changed. <h3>CONCLUSION</h3> Prophylaxis seems to be indicated only for dermal infections, and for infections of the urinary and respiratory tract in patients with increased susceptibility to bacterial arthritis. Prophylaxis for invasive medical procedures, such as dental treatment, may only be indicated for patients with joint disease who are highly susceptible.
FGF23 in Type 2 Diabetic Patients: Relationship With Bone Metabolism and Vascular Disease
Authors: Rebeca Reyes-Garcia, Antonia Garcia-Martín, Beatriz García-Fontana, Sonia Morales-Santana, Pedro Rozas-Moreno, Manuel Muñoz-Torres
Journal: Diabetes Care (2014)

The relationship between fibroblast growth factor (FGF) 23 and vascular disease is well established in chronic kidney disease (CKD). Regarding serum FGF23 and bone fragility, there is contradictory data. Type 2 diabetes (T2D) is associated with higher rates of cardiovascular disease and fractures despite high bone mineral density (BMD), so the evaluation of FGF23 and its relationship with bone and cardiovascular disease in T2D is of interest. Our hypothesis was that serum FGF23 may be related to cardiovascular disease and bone metabolism (BMD, osteoporosis, and fractures) in T2D.

We performed a cross-sectional study including 68 T2D subjects and 45 subjects without diabetes. We analyzed the relationship between circulating FGF23, bone metabolism, cardiovascular events, and intima-media thickness (IMT).

There were no differences in FGF23 according to group. In the …
The insulin/Akt pathway controls a specific cell division program that leads to generation of binucleated tetraploid liver cells in rodents
Authors: Séverine Celton-Morizur, Grégory Merlen, Dominique Couton, Germain Margall-Ducos, Chantal Desdouets
Journal: Journal of Clinical Investigation (2009)

The formation of polyploid cells is part of the developmental program of several tissues. During postnatal development, binucleated tetraploid cells arise in the liver, caused by failure in cytokinesis. In this report, we have shown that the initiation of cytokinesis failure events and the subsequent appearance of binucleated tetraploid cells are strictly controlled by the suckling-to-weaning transition in rodents. We found that daily light/dark rhythms and carbohydrate intake did not affect liver tetraploidy. In contrast, impairment of insulin signaling drastically reduced the formation of binucleated tetraploid cells, whereas repeated insulin injections promoted the generation of these liver cells. Furthermore, inhibition of Akt activity decreased the number of cytokinesis failure events, possibly through the mammalian target of rapamycin signaling complex 2 (mTORC2), which indicates that the PI3K/Akt pathway lies downstream of the insulin signal to regulate the tetraploidization process. To our knowledge, these results are the first demonstration in a physiological context that insulin signaling through Akt controls a specific cell division program and leads to the physiologic generation of binucleated tetraploid liver cells.
Cisplatin and Fluorouracil Concurrent to Radiotherapy in Nasopharyngeal Cancer: Is the Schedule Compatible?
Authors: Lisa Licitra, Paolo Bossi, Laura Locati, Franco Zunino
Journal: Journal of Clinical Oncology (2004)

in an outpatient setting for two cycles, during weeks 1 and 5 of concurrent radiotherapy. Apparently, in this study, an unusual procedure was used to deliver chemotherapy— cisplatin was mixed with fluorouracil in normal saline using an ambulatory pump to allow a 96-hour continuous infusion. The authors state that the adopted schedule was previously evaluated in terms of safety and activity. However, they refer to two studies in which the combination of the two drugs was administered as a 24-hour infusion [2,3]. Cisplatin is a well-known reactive electrophilic agent that is expected to react with a variety of electron-rich nucleophiles. In particular, nucleophilic centers in purines and pyrimidines (eg, ring nitrogen of the bases) are reactive to platinum compounds, resulting in covalent adducts. Indeed, there is evidence of substantial loss of cisplatin in the mixture of cisplatin and fluorouracil [4]. This observation raises important issues concerning the pharmacodynamic basis of the reported combination. It would suggest that the improved efficacy of this schedule, combined with radiotherapy, could be related to the low dose of remaining free cisplatin sufficient to modulate the response to radiotherapy, and/or to the radiosensitizing effect of fluorouracil alone. An alternative explanation is that a putative platinum-fluorouracil adduct is still effective as a cytotoxic agent. Although platinum-modified pyrimidines have been described as active agents, these complexes are poorly characterized [5]. Unexpectedly, a less severe grade 3 to 4 toxicity of leukopenia is reported, in comparison with monochemotherapy with cisplatin at 100 mg/m 2 as used in the Intergroup study [6]. This observation is unusual for the concurrent administration of a polychemotherapy regimen at the total dosages herein reported, thus more resembling that of a low-dose radiosensitizing schedule. Whatever the underlying mechanism of an (inter-)action of the two drugs, the administration modality does not allow a controlled delivery of well-defined molecular species. With such limitations, the study hardly contributes to identifying the optimal schedule of chemotherapy to be concurrently delivered with radiation therapy in nasopharyngeal carcinoma, neither in terms of efficacy nor toxicity.
Bacterial pneumonia as a suprainfection in young adults with measles
Authors: S Loukides, P Panagou, D Kolokouris, N Kalogeropoulos
Journal: European Respiratory Journal (1999)

The aim of this study was to report the clinical and laboratory characteristics of bacterial pneumonia related to measles infection, and also to assess any correlation between severity and time of onset. Four hundred and twenty-four previously healthy young males (age 22+/-2.1 yrs) were hospitalized with typical symptoms and signs of measles. One hundred and twelve (26%) developed bacterial pneumonia on admission (n=41), during their hospital stay (n=20) or days after their discharge (n=51): groups A, B and C, respectively. Single lobar consolidation was the most common finding, accounting for 89% of cases. Pleural effusion was uncommon and associated in half of the cases with empyema. A microbiological diagnosis was made in 81 cases. Streptococcus pneumoniae (65 cases) and Klebsiella pneumoniae (9 cases) were the most commonly identified organisms. Patients from group C had significantly higher values of white blood cell count and erythrocyte sedimentation rate, and lower values of arterial oxygen tension (14+/-0.8 x 10(9) x L(-1), 88+/-4 mm and 6.3+/-0.4 kPa (47+/-3 mmHg), respectively) than the other two groups. There were no deaths during the hospitalization period. The mean duration of hospital stay was 13+/-2.4 days and was longer in the presence of K. pneumoniae infection (19+/-1.6 days). Six patients from group C were admitted to the intensive care unit. In conclusion, these data suggest that bacterial pneumonia associated with measles is not unusual in hospitalized adults, and it seems to be more severe when it occurs days after the onset of rash.