tbuckley/cabot-search huggingface dataset:
Double blind cross-over placebo controlled study of omeprazole in the treatment of patients with reflux symptoms and physiological levels of acid reflux--the "sensitive oesophagus".
Authors: R G Watson, T C Tham, B T Johnston, N I McDougall
Journal: Gut (1997)

BACKGROUND: At least 10-15% of patients with reflux symptoms have a normal endoscopy and physiological levels of acid reflux on pH monitoring. Such patients with 50% or more of symptoms associated with acid reflux episodes have "a positive symptom index" (SI), and it has been proposed that this defines the "sensitive oesophagus". AIM: To test the response to omeprazole 20 mg twice daily for four weeks of patients with normal levels of acid reflux using a randomised, placebo controlled, double blind, cross-over design. PATIENTS: Eighteen patients with normal levels of reflux, 12 of whom had a positive SI. METHODS: Response was measured by symptomatic assessment and the SF-36 quality of life (QOL) questionnaire. RESULTS: Patients with a positive SI showed the following improvements on omeprazole compared with placebo: decrease in symptom frequency (p &lt; 0.01), severity (p &lt; 0.01) and consumption of antacids (p &lt; 0.01). In the group with a negative SI only one patient clearly improved. The QOL parameters for bodily pain (65.6 v 53.4, p = 0.03) and vitality (60.6 v 48.8, p = 0.049) were significantly better on omeprazole than placebo for the group overall. CONCLUSION: Omeprazole improves symptoms in 11 of 18 patients with normal endoscopy and pH monitoring, particularly those with a positive SI. This supports the theory that such patients have an oesophagus which is "sensitive" to acid reflux and are part of the GORD spectrum.
Studies of lactic dehydrogenase content in rectal mucosal biopsies
Authors: P. S. Hunt, P. M. Dennis, P. Jablonski, S. K. Khoo, L. McLeod, H. D. P. Thomson, J. McK. Watts
Journal: Gut (1974)

The total lactic dehydrogenase (LD) content and LD isoenzyme ratios were studied in homogenized rectal mucosa from 31 patients with established non-specific mucosal ulcerative colitis and from 16 normal subjects. The total LD content was found to be significantly increased in patients with active ulcerative colitis when compared with patients with inactive colitis or with normal subjects. There was a similar though not a significant increase in the slow moving isoenzymes of LD in samples of rectal mucosa from patients with active colitis. The LD isoenzyme pattern was in the normal range in two of the three patients with histological premalignant changes in rectal biopsy specimens. There was a statistically significant linear correlation between the total lactic dehydrogenase content of rectal mucosa and the carcino-embryonic antigen levels in whole serum. Both the total content and isoenzyme ratios of LD were increased in neoplastic tissue obtained from patients with carcinoma of the colon and with tissue from benign rectal polyps.
Interactions of tissue-type plasminogen activator with plasma inhibitors and their pharmacologic implications.
Authors: C L Lucore, B E Sobel
Journal: Circulation (1988)

To delineate interactions of infused tissue-type plasminogen activator (t-PA) with inhibitors in plasma and their impact on fibrinolytic activity, serial plasma samples from patients with acute myocardial infarction and from normal rabbits given infusions of t-PA were assayed for t-PA antigen, activity of "fast acting" plasminogen activator inhibitor (PAI-1), and the presence and nature of t-PA-inhibitor complexes. In patients, endogenous t-PA circulated predominantly as a 100 kilodalton (kDa) complex with PAI-1, as verified by immunoprecipitation. During infusions, t-PA circulated not only as free t-PA (55 kDa) but also in complexes with PAI-1 (100 kDa), alpha 2-antiplasmin (110 kDa), and C1-esterase inhibitor (170 kDa). After termination of infusions, levels of free t-PA declined, while inhibitor complexes remained prominent. Free PAI-1 activity, assayed spectrophotometrically, was markedly elevated in the 24 hr interval after infusion of t-PA in 47% of patients with infarction. The specific activity of t-PA during infusions was 0.4 IU/ng or greater. However, during the 3 hr interval after infusions in patients, specific activity declined in association with prominence of t-PA complexes, predominantly with PAI-1. Infusions of t-PA in normal rabbits did not result in reactive increases in PAI-1 activity or in the t-PA-PAI-1 complex. After infusions, t-PA was associated predominantly with alpha 2-antiplasmin and C1-esterase inhibitor rather than PAI-1. t-PA inhibitor complexes were seen despite immediate acidification of whole blood, indicating that they were present in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
[58] SUSTAINED OFF-TREATMENT HBeAg RESPONSE IN TELBIVUDINE AND LAMIVUDINE TREATED HBeAg-POSITIVE PATIENTS FROM THE GLOBE STUDY
Authors: T. Poynard, A. Chutaputti, S.G. Hwang, S.G. Lim, T. Heathcote, Y.Y. Kuan, S. Lee, N. Naoumov, S. Zeuzem, N.A. Brown
Journal: Journal of Hepatology (2007)
Cyclooxygenase 2 mediates post-inflammatory colonic secretory and barrier dysfunction
Authors: S R Zamuner
Journal: Gut (2003)

<b>Background and aims:</b> The colonic epithelium plays a key role in host defence. During colitis, epithelial function is impaired, leading to elevated bacterial translocation and exacerbation of inflammation. We previously documented perturbation of epithelial function, in terms of secretion and as a barrier to bacterial translocation, that persisted long after resolution of a bout of colitis in the rat. The mechanisms underlying the epithelial dysfunction are not completely understood. <b>Methods:</b> Given the ability of prostaglandin (PG) D<sub>2</sub> to suppress colonic epithelial secretion, we investigated the potential roles of this eicosanoid and of cyclooxygenase 2 (COX-2) in mediating post-colitis epithelial secretory and barrier dysfunction. <b>Results:</b> Six weeks after induction of colitis with trinitrobenzene sulphonic acid, there was marked elevated synthesis of PGD<sub>2</sub> and elevated COX-2 expression. Selective COX-2 inhibition abolished the increase in PGD<sub>2</sub> synthesis. Colonic chloride secretory responses (in vitro) were significantly diminished relative to those in controls, a defect that was reversed by pre-exposure to a selective COX-2 inhibitor (celecoxib) but not to a selective COX-1 inhibitor (SC-560). The hyporesponsiveness was mimicked by pre-exposure of normal colonic tissue to PGD<sub>2</sub>, but not to its metabolite, 15-deoxy-Δ<sup>12–14</sup>PGJ<sub>2</sub>. The post-colitis rats exhibited a 10-fold increase in bacterial colonisation of the colon, and &gt;3-fold increase in bacterial translocation. Twice daily treatment for one week with a selective COX-2 inhibitor (rofecoxib) did not affect bacterial colonisation but abolished the increase in bacterial translocation. <b>Conclusions:</b> These studies demonstrate an important role for COX-2, possibly via generation of PGD<sub>2</sub>, in mediating the prolonged epithelial secretory and barrier dysfunction after a bout of colitis in the rat.
Impairment of Transendothelial Leukocyte Migration by Iron Complexes
Authors: Gürkan Sengoelge, Josef Kletzmayr, Ilse Ferrara, Agnes Perschl, Walter H. Hörl, Gere Sunder-Plassmann
Journal: Journal of the American Society of Nephrology (2003)

Although iron sucrose and iron gluconate are generally well tolerated in patients who are treated for renal anemia, recent clinical studies and cell culture experiments suggested significant toxicity and long-term side effects arising from the use of these iron complexes. Because of the possible role of iron in infection or cardiovascular disease, it was theorized that parenteral iron compounds influence endothelial and PMN interaction in vitro. A well-established double-chamber method was used to assess the effect of different concentrations of iron sucrose and iron gluconate (1, 25, 50, and 100 micro g/ml) on the transendothelial migration of PMN. Preincubation of PMN and endothelial cells as well as preincubation of PMN alone with 25, 50, or 100 micro g/ml iron resulted in a significant decrease in PMN migration. In contrast, after incubation of the endothelial cells alone with iron, no reduction in the transendothelial migration of PMN was observed. Preincubation of PMN and/or endothelial cells with 1 micro g/ml iron did not lead to any decrease in the rate of migrated PMN. The only significant change in experiments with 1 micro g/ml was an increase in PMN migration after preincubation of endothelial cells and PMN with iron gluconate. A four-way ANOVA showed a significant effect of the iron concentration (P < 0.000001), of type of iron complex (P < 0.005), of the preincubation of endothelial cell (P < 0.001), and of the preincubation of PMN with iron (P < 0.000001) on PMN diapedesis. It is concluded that iron sucrose and iron gluconate cause a significant inhibition of transendothelial migration of PMN.
Imaging of the Porous Ultrastructure of the Glomerular Epithelial Filtration Slit
Authors: Elena Gagliardini, Sara Conti, Ariela Benigni, Giuseppe Remuzzi, Andrea Remuzzi
Journal: Journal of the American Society of Nephrology (2010)

The ultrastructure of the glomerular filtration slit is still controversial. In the last 30 years, observations from transmission electron microscopy (TEM) and theoretical analysis of solute clearance produced conflicting results. Here, we used scanning EM with a high-sensitivity detector to image the deepest regions of the filtration slits and report a previously undescribed organization of the slits' ultrastructure. In contrast to previous TEM imaging, we observed circular and ellipsoidal pores in the podocyte junctions mainly located in the central region of the slit diaphragm. The normal mean pore radius estimated by digital morphometric analysis had a log-normal distribution, with an average value of 12.1 nm. In proteinuric pathologic conditions, the mean pore radius values were also log-normally distributed with the presence of some very large pores, exceeding the sizes observed in normal conditions. Our morphologic analysis suggests that the filtration slit is a heteroporous structure instead of the previously proposed zipper-like structure. Selective changes in the ultrastructural organization of the pores may be responsible for the increased filtration of plasma proteins in glomerular disease.
Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial
Authors: Paul G. Richardson, Pieter Sonneveld, Michael Schuster, David Irwin, Edward Stadtmauer, Thierry Facon, Jean-Luc Harousseau, Dina Ben-Yehuda, Sagar Lonial, Hartmut Goldschmidt, Donna Reece, Jesus San Miguel, Joan Bladé, Mario Boccadoro, Jamie Cavenagh, Melissa Alsina, S. Vincent Rajkumar, Martha Lacy, Andrzej Jakubowiak, William Dalton, Anthony Boral, Dixie-Lee Esseltine, David Schenkein, Kenneth C. Anderson
Journal: Blood (2007)
Extremely severe palmoplantar hyperkeratosis in a generalized epidermolytic hyperkeratosis patient with a keratin 1 gene mutation
Authors: Rinko Osawa, Masashi Akiyama, Kentaro Izumi, Hideyuki Ujiie, Kaori Sakai, Ikue Nemoto-Hasebe, Teruki Yanagi, Hiroko Koizumi, Hiroshi Shimizu
Journal: Journal of the American Academy of Dermatology (2011)
Common Genetic Variation at the Endothelial Nitric Oxide Synthase Locus and Relations to Brachial Artery Vasodilator Function in the Community
Authors: Sekar Kathiresan, Martin G. Larson, Ramachandran S. Vasan, Chao-Yu Guo, Joseph A. Vita, Gary F. Mitchell, Michelle J. Keyes, Christopher Newton-Cheh, Stacy L. Musone, Amy L. Lochner, Jared A. Drake, Daniel Levy, Christopher J. O’Donnell, Joel N. Hirschhorn, Emelia J. Benjamin
Journal: Circulation (2005)

Sequence variants at the endothelial nitric oxide synthase (NOS3) locus have been associated with endothelial function measures, but replication has been limited.In reference pedigrees, we characterized linkage disequilibrium structure at the NOS3 locus using 33 common single nucleotide polymorphisms (SNPs). Eighteen SNPs that capture underlying common variation were genotyped in unrelated Framingham Heart Study participants (49.5% women; mean age, 62 years) with measured brachial artery flow-mediated dilation (n=1446) or hyperemic flow velocity (n=1043). Within 3 defined blocks of strong linkage disequilibrium that spanned NOS3, 11 SNPs captured >80% of common haplotypic variation. Among men, there were nominally significant associations between 8 NOS3 SNPs (minimum P=0.002) and between haplotypes (minimum P=0.002) and either flow-mediated dilation or hyperemic flow velocity. In women, we did not observe significant associations between NOS3 SNPs or haplotypes and endothelial function measures. To correct for multiple testing, we constructed 1000 bootstrapped null data sets and found that empirical probability values exceeded 0.05 for both phenotypes.A parsimonious set of SNPs captures common genetic variation at the NOS3 locus. A conservative interpretation of our results is that, accounting for multiple testing, we did not observe statistically significant relations between NOS3 sequence variants and endothelial function measures in either sex. The nominal associations of select NOS3 variants with endothelial function in men (unadjusted for multiple testing) should be viewed as hypothesis-generating observations and may merit testing in other cohorts and experimental designs.
Ocular injury in hurling
Authors: T H Flynn, K Fennessy, N Horgan, B Walsh, E O’Connell, P Cleary, S Beatty
Journal: British Journal of Sports Medicine (2005)

Objectives: To describe the clinical characteristics of ocular injuries sustained in hurling in the south of Ireland and to investigate reasons for non-use of protective headgear and eye wear. Methods: Retrospective review of the case notes of 310 patients who attended Cork University Hospital or Waterford Regional Hospital between 1 January 1994 and 31 December 2002 with ocular injuries sustained during a hurling match. A confidential questionnaire on reasons for non-use of protective headgear and eye wear was completed by 130 players. Results: Hurling related eye injuries occurred most commonly in young men. Fifty two patients (17%) required hospital admission, with hyphaema accounting for 71% of admissions. Ten injuries required intraocular surgical intervention: retinal detachment repair (5); macular hole surgery (1); repair of partial thickness corneal laceration (1); repair of globe perforation (1); enucleation (1); trabeculectomy for post-traumatic glaucoma (1). Fourteen eyes (4.5%) had a final best corrected visual acuity (BCVA) of &lt;6/12 and six (2%) had BCVA &lt;3/60. In the survey, 63 players (48.5%) reported wearing no protective facemask while playing hurling. Impairment of vision was the most common reason cited for non-use. Conclusions: Hurling related injury is a significant, and preventable, cause of ocular morbidity in young men in Ireland. The routine use of appropriate protective headgear and faceguards would result in a dramatic reduction in the incidence and severity of these injuries, and should be mandatory.
Excess lung function decline in gold miners following pulmonary tuberculosis
Authors: J. Ross, R. I. Ehrlich, E. Hnizdo, N. White, G. J. Churchyard
Journal: Thorax (2010)

<h3>Background</h3> Few if any studies of the association between pulmonary tuberculosis (TB) and lung function loss have had access to premorbid lung function values. <h3>Methods</h3> Using a retrospective cohort design, the study recruited employed South African gold miners who had undergone a pulmonary function test (PFT) between January 1995 and August 1996. The 'exposed' group comprised 185 miners treated for pulmonary TB after the initial PFT and the 'unexposed' group comprised 185 age-matched miners without TB. All participants had a follow-up PFT between April and June 2000. The outcome of interest was decline in lung function during the follow-up period as measured by forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV<sub>1</sub>). <h3>Results</h3> After controlling for age, height, baseline lung function, silicosis, years of employment, smoking and other respiratory diagnoses, pulmonary TB during the follow-up period was associated with a mean excess loss of 40.3 ml/year in FEV<sub>1</sub> (95% CI 25.4 to 55.1) and 42.7 ml/year in FVC (95% CI 27.0 to 58.5). Lung function loss was greater among those with more severe or later clinical presentation of TB. Breathlessness was twice as common among TB cases (OR 2.20, 95% CI 1.18 to 4.11). <h3>Conclusion</h3> There is a need for greater clinical recognition of the long-term respiratory consequences of treated pulmonary TB. Early detection of TB would help to reduce these sequelae and remains a priority, particularly in a workforce already subject to silica dust disease. However, strategies such as dust control, worker education about TB and dust and TB preventive therapy are also needed to avert the disease itself.
A Heme-Sensing Mechanism in the Translational Regulation of Mitochondrial Cytochrome c Oxidase Biogenesis
Authors: Iliana C. Soto, Flavia Fontanesi, Richard S. Myers, Patrice Hamel, Antoni Barrientos
Journal: Cell Metabolism (2012)

Heme plays fundamental roles as cofactor and signaling molecule in multiple pathways devoted to oxygen sensing and utilization in aerobic organisms. For cellular respiration, heme serves as a prosthetic group in electron transfer proteins and redox enzymes. Here we report that in the yeast Saccharomyces cerevisiae, a heme-sensing mechanism translationally controls the biogenesis of cytochrome c oxidase (COX), the terminal mitochondrial respiratory chain enzyme. We show that Mss51, a COX1 mRNA-specific translational activator and Cox1 chaperone, which coordinates Cox1 synthesis in mitoribosomes with its assembly in COX, is a heme-binding protein. Mss51 contains two heme regulatory motifs or Cys-Pro-X domains located in its N terminus. Using a combination of in vitro and in vivo approaches, we have demonstrated that these motifs are important for heme binding and efficient performance of Mss51 functions. We conclude that heme sensing by Mss51 regulates COX biogenesis and aerobic energy production.
The paradox in pneumococcal serotypes: highly invasive does not mean highly lethal
Authors: M.W. Pletz, T. Welte, K.P. Klugman
Journal: European Respiratory Journal (2010)

S treptococcus pneumoniae is a major bacterial pathogen and a predominant cause of community-acquired pneumonia, acute exacerbations of chronic bronchitis, meningitis, sinusitis and bacteraemia in both developed and developing countries. Each year millions of people die from pneumococcal diseases. Even in developed countries, the case-fatality rate of pneumococcal pneumonia is still high 1. This is in contrast to the fact that 1) appropriate antibiotic treatment is available, and 2) to date, antimicrobial resistance rates of pneumococci for non-meningeal infections are still low in most countries or antimicrobial resistance ( e.g. penicillin-resistance) is not related to treatment failure in pneumococcal pneumonia 2. A considerable number of patients die within the first 48 h and these early deaths have not been prevented by antibiotic treatment 3.

Brueggemann et al. 4 investigated the risk of different pneumococcal serotypes to cause invasive disease. Invasive pneumococcal disease is defined as the isolation of S. pneumoniae from a normally sterile site, e.g. blood, cerebrospinal fluid or pleural fluid. The polysaccharide capsule protects pneumococci from phagocytosis and also may determine affinity to respiratory epithelium. Therefore, it seems reasonable that different pneumococcal …
Randomized, Placebo-Controlled Study for Immunosuppressive Treatment of Inflammatory Dilated Cardiomyopathy
Authors: Romuald Wojnicz, Ewa Nowalany-Kozielska, Celina Wojciechowska, Grażyna Glanowska, Przemysław Wilczewski, Tomasz Niklewski, Marian Zembala, Lech Poloński, Marius M. Rozek, Jan Wodniecki
Journal: Circulation (2001)

Background —Previous studies have shown disappointing results for immunosuppressive treatment in patients with dilated cardiomyopathy. Therefore, we studied the effectiveness of such therapy in patients with HLA upregulation on biopsy. Methods and Results —Of 202 patients with dilated cardiomyopathy, 84 patients with increased HLA expression were randomized to receive either immunosuppression or placebo for 3 months; they were then followed for 2 years. After 2 years, there were no significant differences in the primary end point (a composite of death, heart transplantation, and hospital readmission) between the 2 study groups (22.8% for the immunosuppression group and 20.5% for the placebo). The secondary efficacy end point included changes in ejection fraction, end-diastolic diameter, end-diastolic volume, end-systolic volume and NYHA class; left ventricular ejection fraction increased significantly in the immunosuppression group compared with the placebo group (95% CI, 4.20 to 13.12; P &lt;0.001) after 3 months of follow-up. The early favorable effects of immunosuppressive therapy on left ventricular volume, left ventricular diastolic dimension, and New York Heart Association class were also present. This improvement was maintained in the immunosuppression group at 2 years (ejection fraction: 95% CI, 6.94 to 19.04; P &lt;0.001). In addition, on the basis of the protocol-specified definition of improvement, 71.8% patients in the immunosuppression group versus 20.9% patients in the placebo group met the criteria of improvement after 3 months ( P &lt;0.001). At the end of the follow-up period, 71.4% patients from the immunosuppression group versus 30.8% patients from the placebo group were improved ( P =0.001). Conclusions —These data demonstrate a long-term benefit of immunosuppressive therapy in patients with dilated cardiomyopathy and HLA upregulation on biopsy specimens. Thus, restoration of immunosuppressive therapy for such patients should be considered.
Unscheduled expression of CDC25B in S-phase leads to replicative stress and DNA damage
Authors: Béatrix Bugler, Estelle Schmitt, Bernadette Aressy, Bernard Ducommun
Journal: Molecular Cancer (2010)

Abstract Background CDC25B phosphatase is a cell cycle regulator that plays a critical role in checkpoint control. Up-regulation of CDC25B expression has been documented in a variety of human cancers, however, the relationships with the alteration of the molecular mechanisms that lead to oncogenesis still remain unclear. To address this issue we have investigated, in model cell lines, the consequences of unscheduled and elevated CDC25B levels. Results We report that increased CDC25B expression leads to DNA damage in the absence of genotoxic treatment. H2AX phosphorylation is detected in S-phase cells and requires active replication. We also report that CDC25B expression impairs DNA replication and results in an increased recruitment of the CDC45 replication factor onto chromatin. Finally, we observed chromosomal aberrations that are also enhanced upon CDC25B expression. Conclusion Overall, our results demonstrate that a moderate and unscheduled increase in CDC25B level, as observed in a number of human tumours, is sufficient to overcome the S-phase checkpoint efficiency thus leading to replicative stress and genomic instability.