tbuckley/cabot-search huggingface dataset:
Regulation of granulomatous inflammation in murine schistosomiasis. In vitro characterization of T lymphocyte subsets involved in the production and suppression of migration inhibition factor.
Authors: S W Chensue, D L Boros, C S David
Journal: The Journal of Experimental Medicine (1980)

Host granulomatous inflammation in murine schistosomiasis mansoni is a T cell-mediated immune response, which, at the chronic stage of the disease, undergoes T suppressor lymphocyte-dependent modulation. In the present study this phenomenon was further analyzed in vitro. Spleen cells of mice undergoing modulation (20 wk of infection) when mixed with spleen cells of animals exhibiting vigorous granulomatous responses (8 wk of infection) abrogated in vitro migration inhibition factor (MIF) production by the latter. Characterization of the delayed-type hypersensitivity T lymphocytes involved in lymphokine production showed that they belonged to the Lyt-1+ subset and did not express I region-encoded antigens. In contrast, T lymphocytes involved in the suppression of MIF activity belonged to the Lyt-2+ subpopulation of cells, which expressed I-J- and I-C-subregion determinants. These results suggest that the modulation of the granulomatous hypersensitivity response in mice is the result of T-T cell interaction with subsequent regulation of inflammatory lymphokine production.
Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury.
Authors: T Jocks, G Zahner, J Freudenberg, G Wolf, F Thaiss, U Helmchen, R A Stahl
Journal: Journal of the American Society of Nephrology (1996)

To study whether prostaglandins (PG) can regulate the mRNA expression of monocyte-chemoattractant protein 1 (MCP-1) in glomerular immune injury, MCP-1 mRNA levels were evaluated in anti-thymocyte antibody (ATS) -induced glomerular injury by Northern blotting and reverse transcription-polymerase chain reaction. Immune injury was induced in vivo by the intravenous application of ATS to male Wistar rats and in vitro by the perfusion of isolated rat kidneys with ATS and rat serum. In vivo 3 h and 5 days after antibody application, glomerular mRNA expression of MCP-1 was markedly enhanced compared with controls. In the isolated perfused kidney, antibody and complement also induced an increase in MCP-1 expression at 10 min and 60 min after antibody perfusion. When the rats were treated with PGE (250 micrograms, twice daily), the increase in MCP-1 expression was reduced. This was associated with a reduction of intraglomerular recruitment of monocytes/macrophages. In the isolated perfused kidneys, PGE1 (1 mg/L) prevented the antibody- and rat serum-stimulated increase in glomerular MCP-1 mRNA expression. These data demonstrate that PGE1 reduces glomerular MCP-1 mRNA expression in glomerulonephritis and in the isolated perfused rat kidney after induction of immune injury with antibody and complement. The data suggest that prostaglandins might mediate MCP-1 effects in glomerular immune injuries.
Maternal 25-hydroxyvitamin D levels in relation to offspring respiratory symptoms and infections
Authors: R. T. de Jongh, S. R. Crozier, S. D'Angelo, K. C. Pike, G. Roberts, J. S. A. Lucas, H. Inskip, K. M. Godfrey, C. Cooper, N. C. Harvey
Journal: European Respiratory Journal (2013)

Maternal 25-hydroxyvitamin D levels in relation to offspring respiratory symptoms and infectionsTo the Editor:Recently, there has been an increasing interest in the immunomodulatory effects of vitamin D. Several studies have suggested detrimental effects of insufficient 25-hydroxyvitamin D (25(OH)D) levels on the innate and acquired immune system, which may contribute to the development of infections and atopic and allergic conditions [1][2][3][4].Children and pregnant and lactating females have been identified as groups with a high risk of 25(OH)D insufficiency [5].Low maternal serum 25(OH)D levels in pregnancy may contribute to increased risk of infections and atopic outcomes in offspring.Previous studies demonstrate inconsistency regarding relationships between maternal vitamin D intake, serum 25(OH)D levels and umbilical cord 25(OH)D levels with these outcomes in offspring [6][7][8][9][10].We aimed to explore relationships between maternal serum 25(OH)D levels during late pregnancy and parent-reported respiratory tract symptoms and doctor-diagnosed lower respiratory tract infections (LRTI) in early childhood in a large cohort study.
A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer
Authors: M.L. Rothenberg, M.J. Moore, M.C. Cripps, J.S. Andersen, R.K. Portenoy, H.A. Burriss, M.R. Green, P.G. Tarassoff, T.D. Brown, E.S. Casper, A.-M. Storniolo, D.D. Von Hoff
Journal: Annals of Oncology (1996)
Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial
Authors: Jörg Ederle, Leo H Bonati, Joanna Dobson, Roland L Featherstone, Peter A Gaines, Jonathan D Beard, Graham S Venables, Hugh S Markus, Andrew Clifton, Peter Sandercock, Martin M Brown
Journal: The Lancet Neurology (2009)

Endovascular treatment (angioplasty with or without stenting) is an alternative to carotid endarterectomy for carotid artery stenosis but there are scarce long-term efficacy data showing that it prevents stroke. We therefore report the long-term results of the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS).Between March, 1992, and July, 1997, patients who presented at a participating centre with a confirmed stenosis of the internal carotid artery that was deemed equally suitable for either carotid endarterectomy or endovascular treatment were randomly assigned to either treatment in equal proportions by telephone or fax from the randomisation service at the Oxford Clinical Trials Unit, UK. Patients were seen by an independent neurologist at 1 and 6 months after treatment and then every year after randomisation for as long as possible, up to a maximum of 11 years. Major outcome events were transient ischaemic attack, non-disabling, disabling, and fatal stroke, myocardial infarction, and death from any other cause. Outcomes were adjudicated on by investigators who were masked to treatment. Analysis was by intention to treat. This study is registered, number ISRCTN 01425573.504 patients with stenosis of the carotid artery (90% symptomatic) were randomly assigned to endovascular treatment (n=251) or surgery (n=253). Within 30 days of treatment, there were more minor strokes that lasted less than 7 days in the endovascular group (8 vs 1) but the number of other strokes in any territory or death was the same (25 vs 25). There were more cranial nerve palsies (22 vs 0) in the endarterectomy group than in the endovascular group. Median length of follow up in both groups was 5 years (IQR 2-6). By comparing endovascular treatment with endarterectomy after the 30-day post-treatment period, the 8-year incidence and hazard ratio (HR) at the end of follow-up for ipsilateral non-perioperative stroke was 11.3% versus 8.6% (HR 1.22, 95% CI 0.59-2.54); for ipsilateral non-perioperative stroke or TIA was 19.3% versus 17.2% (1.29, 0.78-2.14); and for any non-perioperative stroke was 21.1% versus 15.4% (1.66, 0.99-2.80).More patients had stroke during follow-up in the endovascular group than in the surgical group, but the rate of ipsilateral non-perioperative stroke was low in both groups and none of the differences in the stroke outcome measures was significant. However, the study was underpowered and the confidence intervals were wide. More long-term data are needed from the on going stenting versus endarterectomy trials.British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.
Impact of resistance to first-line and injectable drugs on treatment outcomes in MDR-TB
Authors: S. S. Hwang, H-R. Kim, H. J. Kim, M. J. Kim, S. M. Lee, C-G. Yoo, Y. W. Kim, S. K. Han, Y-S. Shim, J-J. Yim
Journal: European Respiratory Journal (2009)

Recently, resistance to additional first-line and injectable drugs was reported to be an independent risk factor for adverse outcomes in multidrug-resistant (MDR) tuberculosis (TB) patients. The aim of the present study was to confirm these observations in MDR-TB patients without HIV infection. MDR-TB patients treated at a tertiary referral hospital in South Korea between January 1996 and December 2005 were included. The unadjusted and adjusted odds ratios of adverse treatment outcome were calculated for resistance to each drug and combination of drugs using simple or multiple logistic regressions. None of the resistance to additional first-line or injectable drugs was associated with higher odds for adverse treatment outcome in 155 MDR but nonextensively drug-resistant (non-XDR) TB patients. However, streptomycin resistance was associated with 12 times the odds for adverse treatment outcome in 42 extensively drug-resistant (XDR) TB patients. Neither combinations of first-line drugs nor those of injectable drugs were associated with increased odds for adverse treatment outcomes in non-XDR MDR-TB patients or XDR-TB patients. Only streptomycin resistance among the first-line or injectable drugs was associated with adverse treatment outcomes in extensively drug-resistant tuberculosis patients without HIV infection.
Intensive Intraoperative Insulin Therapy versus Conventional Glucose Management during Cardiac Surgery
Authors: Gunjan Y. Gandhi, Gregory A. Nuttall, Martin D. Abel, Charles J. Mullany, Hartzell V. Schaff, Peter C. O'Brien, Matthew G. Johnson, Arthur R. Williams, Susanne M. Cutshall, Lisa M. Mundy, Robert A. Rizza, M. Molly McMahon
Journal: Annals of Internal Medicine (2007)

Background: It is not known whether rigorous intraoperative glycemic control reduces death and morbidity in cardiac surgery patients. Objective: To compare outcomes of intensive insulin therapy during cardiac surgery with those of conventional intraoperative glucose management. Design: A randomized, open-label, controlled trial with blinded end point assessment. Setting: Tertiary care center. Patients: Adults with and without diabetes who were undergoing on-pump cardiac surgery. Measurements: The primary outcome was a composite of death, sternal infections, prolonged ventilation, cardiac arrhythmias, stroke, and renal failure within 30 days after surgery. Secondary outcome measures were length of stay in the intensive care unit and hospital. Intervention: Patients were randomly assigned to receive continuous insulin infusion to maintain intraoperative glucose levels between 4.4 (80 mg/dL) and 5.6 mmol/L (100 mg/dL) (n = 199) or conventional treatment (n = 201). Patients in the conventional treatment group were not given insulin during surgery unless glucose levels were greater than 11.1 mmol/L (>200 mg/dL). Both groups were treated with insulin infusion to maintain normoglycemia after surgery. Results: Mean glucose concentrations were statistically significantly lower in the intensive treatment group at the end of surgery (6.3 mmol/L [SD, 1.6] [114 mg/dL {SD, 29}] in the intensive treatment group vs. 8.7 mmol/L [SD, 2.3] [157 mg/dL {SD, 42}] in the conventional treatment group; difference, −2.4 mmol/L [95% CI, −2.8 to −1.9 mmol/L] [−43 mg/dL {CI, −50 to −35 mg/dL}]). Eighty two of 185 patients (44%) in the intensive treatment group and 86 of 186 patients (46%) in the conventional treatment group had an event (risk ratio, 1.0 [CI, 0.8 to 1.2]). More deaths (4 deaths vs. 0 deaths; P = 0.061) and strokes (8 strokes vs. 1 strokes; P = 0.020) occurred in the intensive treatment group. Length of stay in the intensive care unit (mean, 2 days [SD, 2] vs. 2 days [SD, 3]; difference, 0 days [CI, −1 to 1 days]) and in the hospital (mean, 8 days [SD, 4] vs. 8 days [SD, 5]; difference, 0 days [CI, −1 to 0 days]) was similar for both groups. Limitations: This single-center study used a composite end point and could not examine whether outcomes differed by diabetes status. Conclusions: Intensive insulin therapy during cardiac surgery does not reduce perioperative death or morbidity. The increased incidence of death and stroke in the intensive treatment group raises concern about routine implementation of this intervention.
Mature Follicular Dendritic Cell Networks Depend on Expression of Lymphotoxin β Receptor by Radioresistant Stromal Cells and of Lymphotoxin β and Tumor Necrosis Factor by B Cells
Authors: Robert Endres, Marat B. Alimzhanov, Thomas Plitz, Agnes Fütterer, Marie H. Kosco-Vilbois, Sergei A. Nedospasov, Klaus Rajewsky, Klaus Pfeffer
Journal: The Journal of Experimental Medicine (1999)

The formation of germinal centers (GCs) represents a crucial step in the humoral immune response. Recent studies using gene-targeted mice have revealed that the cytokines tumor necrosis factor (TNF), lymphotoxin (LT) alpha, and LTbeta, as well as their receptors TNF receptor p55 (TNFRp55) and LTbetaR play essential roles in the development of GCs. To establish in which cell types expression of LTbetaR, LTbeta, and TNF is required for GC formation, LTbetaR-/-, LTbeta-/-, TNF-/-, B cell-deficient (BCR-/-), and wild-type mice were used to generate reciprocal or mixed bone marrow (BM) chimeric mice. GCs, herein defined as peanut agglutinin-binding (PNA+) clusters of centroblasts/centrocytes in association with follicular dendritic cell (FDC) networks, were not detectable in LTbetaR-/- hosts after transfer of wild-type BM. In contrast, the GC reaction was restored in LTbeta-/- hosts reconstituted with either wild-type or LTbetaR-/- BM. In BCR-/- recipients reconstituted with compound LTbeta-/-/BCR-/- or TNF-/-/BCR-/- BM grafts, PNA+ cell clusters formed in splenic follicles, but associated FDC networks were strongly reduced or absent. Thus, development of splenic FDC networks depends on expression of LTbeta and TNF by B lymphocytes and LTbetaR by radioresistant stromal cells.
Rapid Evolution of Immune Proteins in Social Insects
Authors: L. Viljakainen, J. D. Evans, M. Hasselmann, O. Rueppell, S. Tingek, P. Pamilo
Journal: Molecular Biology and Evolution (2009)

The existence of behavioral traits connected to defense against pathogens manifests the importance of pathogens in the evolution of social insects. However, very little is known about how pathogen pressure has affected the molecular evolution of genes involved in their innate immune system. We have studied the sequence evolution of several immune genes in ants and honeybees. The results show high rates of evolution in both ants and honeybees as measured by the ratio of amino acid changes to silent nucleotide changes, the ratio being clearly higher than in Drosophila immune genes or in nonimmunity genes of bees. This conforms to our expectations based on high pathogen pressure in social insects. The codon-based likelihood method found clear evidence of positive selection only in one ant gene, even though positive selection has earlier been found in both ant and termite immune genes. There is now indication that selection on the amino acid composition of the immune-related genes has been an important part in the fight against pathogens by social insects. However, we cannot distinguish in all the cases whether the high observed dN/dS ratio results from positive selection within a restricted part of the studied genes or from relaxation of purifying selection associated with effective measures of behaviorally based colony-level defenses.
Interphase Fluorescence <i>In situ</i> Hybridization Analysis of Chromosome 12p Abnormalities Is Useful for Distinguishing Epidermoid Cysts of the Testis from Pure Mature Teratoma
Authors: Liang Cheng, Shaobo Zhang, Gregory T. MacLennan, Christopher K. Poulos, Ming-Tse Sung, Stephen D. Beck, Richard S. Foster
Journal: Clinical Cancer Research (2006)

The distinction of epidermoid cyst of the testis from teratoma is of critical importance because the former is benign and the latter is a malignant tumor that may have associated metastasis of either teratomatous or non-teratomatous germ cell tumor types. Chromosome 12p abnormalities are seen in the vast majority of testicular germ cell tumors of adults and are present in all histologic subtypes. In this study, we investigated the clinical utility of interphase fluorescence in situ hybridization (FISH) analysis of chromosome 12p abnormalities for distinguishing epidermoid cysts of the testis from pure mature teratoma.Sixteen testicular epidermoid cysts and 17 testicular teratomas were investigated for isochromosome 12p [i(12p)] and 12p overrepresentation using interphase FISH analysis.Neither i(12p) nor 12p overrepresentation were observed in 16 epidermoid cyst cases, whereas i(12p) was detected in 76% of teratomas and 12p overrepresentation was identified in 29% of teratomas. Overall, 88% of testicular teratomas had chromosome 12p abnormalities.FISH identification of i(12p) and/or 12p overrepresentation in routinely processed surgical specimens is a useful ancillary diagnostic tool in distinguishing testicular epidermoid cysts from teratoma.
Beneficial effects of exercise: shifting the focus from body weight to other markers of health
Authors: N A King, M Hopkins, P Caudwell, R J Stubbs, J E Blundell
Journal: British Journal of Sports Medicine (2009)

Background: Exercise is widely promoted as a method of weight management, while the other health benefits are often ignored. The purpose of this study was to examine whether exercise-induced improvements in health are influenced by changes in body weight. Methods: Fifty-eight sedentary overweight/obese men and women (BMI 31.8 (SD 4.5) kg/m 2 ) participated in a 12-week supervised aerobic exercise intervention (70% heart rate max, five times a week, 500 kcal per session). Body composition, anthropometric parameters, aerobic capacity, blood pressure and acute psychological response to exercise were measured at weeks 0 and 12. Results: The mean reduction in body weight was −3.3 (3.63) kg (p&lt;0.01). However, 26 of the 58 participants failed to attain the predicted weight loss estimated from individuals’ exercise-induced energy expenditure. Their mean weight loss was only −0.9 (1.8) kg (p&lt;0.01). Despite attaining a lower-than-predicted weight reduction, these individuals experienced significant increases in aerobic capacity (6.3 (6.0) ml/kg/min; p&lt;0.01), and a decreased systolic (−6.00 (11.5) mm Hg; p&lt;0.05) and diastolic blood pressure (−3.9 (5.8) mm Hg; p&lt;0.01), waist circumference (−3.7 (2.7) cm; p&lt;0.01) and resting heart rate (−4.8 (8.9) bpm, p&lt;0.001). In addition, these individuals experienced an acute exercise-induced increase in positive mood. Conclusions: These data demonstrate that significant and meaningful health benefits can be achieved even in the presence of lower-than-expected exercise-induced weight loss. A less successful reduction in body weight does not undermine the beneficial effects of aerobic exercise. From a public health perspective, exercise should be encouraged and the emphasis on weight loss reduced.
Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2
Authors: G Paizis, Christos Tikellis, M E Cooper, J M Schembri, Rebecca A Lew, Alexander Ian Smith, T Shaw, Fiona Jane Warner, A Zuilli, Louise M Burrell, Peter W Angus
Journal: Gut (2005)

<b>Background:</b> Angiotensin converting enzyme (ACE) 2 is a recently identified homologue of ACE that may counterregulate the actions of angiotensin (Ang) II by facilitating its breakdown to Ang 1–7. The renin-angiotensin system (RAS) has been implicated in the pathogenesis of cirrhosis but the role of ACE2 in liver disease is not known. <b>Aims:</b> This study examined the effects of liver injury on ACE2 expression and activity in experimental hepatic fibrosis and human cirrhosis, and the effects of Ang 1–7 on vascular tone in cirrhotic rat aorta. <b>Methods:</b> In sham operated and bile duct ligated (BDL) rats, quantitative reverse transcriptase-polymerase chain reaction was used to assess hepatic ACE2 mRNA, and western blotting and immunohistochemistry to quantify and localise ACE2 protein. ACE2 activity was quantified by quenched fluorescent substrate assay. Similar studies were performed in normal human liver and in hepatitis C cirrhosis. <b>Results:</b> ACE2 mRNA was detectable at low levels in rat liver and increased following BDL (363-fold; p&lt;0.01). ACE2 protein increased after BDL (23.5-fold; p&lt;0.05) as did ACE2 activity (fourfold; p&lt;0.05). In human cirrhotic liver, gene (&gt;30-fold), protein expression (97-fold), and activity of ACE2 (2.4 fold) were increased compared with controls (all p&lt;0.01). In healthy livers, ACE2 was confined to endothelial cells, occasional bile ducts, and perivenular hepatocytes but in both BDL and human cirrhosis there was widespread parenchymal expression of ACE2 protein. Exposure of cultured human hepatocytes to hypoxia led to increased ACE2 expression. In preconstricted rat aorta, Ang 1–7 alone did not affect vascular tone but it significantly enhanced acetylcholine mediated vasodilatation in cirrhotic vessels. <b>Conclusions:</b> ACE2 expression is significantly increased in liver injury in both humans and rat, possibly in response to increasing hepatocellular hypoxia, and may modulate RAS activity in cirrhosis.
Zisupton--A Novel Superfamily of DNA Transposable Elements Recently Active in Fish
Authors: A. Bohne, Q. Zhou, A. Darras, C. Schmidt, M. Schartl, D. Galiana-Arnoux, J.-N. Volff
Journal: Molecular Biology and Evolution (2011)

Transposable elements are widespread mobile DNA sequences able to integrate into new locations within genomes. Through transposition and recombination, they significantly contribute to genome plasticity and evolution. They can also regulate gene expression and provide regulatory and coding sequences (CDSs) for the evolution of novel gene functions. We have identified a new superfamily of DNA transposon on the Y chromosome of the platyfish Xiphophorus maculatus. This element is 11 kb in length and carries a single CDS of 24 exons. The N-terminal part of the putative protein, which is expressed in all adult tissues tested, contains several nucleic acid– and protein-binding domains and might correspond to a novel type of transposase/integrase not described so far in any transposon. In addition, a testis-specific splice isoform encodes a C-terminal Ulp1 SUMO protease domain, suggesting a function in posttranslational protein modification mediated by SUMO and/or ubiquitin small peptides. Accordingly, this element was called Zisupton, for Zinc finger SUMO protease transposon. Beside the Y-chromosomal sequence, five other very similar copies were identified in the platyfish genome. All copies are delimited by 99-bp conserved subterminal inverted repeats and flanked by copy-specific 8-nt target site duplications reflecting their integration at different positions in the genome. Zisupton elements are inserted at different genomic locations in different poeciliid species but also in different populations of X. maculatus. Such insertion polymorphisms between related species and populations indicate relatively recent transposition activity, with a high degree of nucleotide identity between species suggesting possible implication of horizontal gene transfer. Zisupton sequences were detected in other fish species, in urochordates, cephalochordates, and hemichordates as well as in more distant organisms, such as basidiomycete fungi, filamentous brown algae, and green algae. Possible examples of nuclear genes derived from Zisupton have been identified. To conclude, our analysis has uncovered a new superfamily of DNA transposons with potential roles in genome diversity and evolutionary innovation in fish and other organisms.