tbuckley/cabot-search huggingface dataset:
Interleukin-18 Is a Strong Predictor of Cardiovascular Events in Elderly Men With the Metabolic Syndrome
Authors: Marius Trøseid, Ingebjørg Seljeflot, Elsa M. Hjerkinn, Harald Arnesen
Journal: Diabetes Care (2008)

OBJECTIVE—The aim of this study was to investigate the role of inflammatory markers as potential predictors of cardiovascular events in subjects with and without the metabolic syndrome. RESEARCH DESIGN AND METHODS—This was a post hoc analysis from the Diet and Omega-3 Intervention Trial (DOIT), comprising 563 elderly men with (n = 221) and without (n = 342) metabolic syndrome. Circulating inflammatory markers were measured. RESULTS—During 3 years, 68 cardiovascular events were recorded. In the total population, C-reactive protein (CRP) (P &amp;lt; 0.001), interleukin-18 (IL-18) (P = 0.008), and IL-6 (P = 0.003) were elevated in subjects with events. In subjects with metabolic syndrome, IL-18 was the strongest predictor (adjusted odds ratio 2.9 [95% CI 1.1–7.8]). In subjects without metabolic syndrome, only CRP seemed to be an independent predictor (3.3 [1.5–7.3]). There was a significant interaction between fasting glucose and IL-18 (P = 0.008) and IL-6 (P = 0.024) but not CRP. Elevated fasting glucose (&amp;gt;6.2 mmol/l) markedly increased the predictive power of inflammatory markers (IL-18: 5.5 [1.4–21.1], IL-6: 3.5 [1.0–11.8], and CRP: 3.5 [1.0–11.9]). For IL-18, there was a stepwise increase in event rate by quartiles of fasting glucose. CONCLUSIONS—IL-18 was an independent predictor of cardiovascular events in subjects with metabolic syndrome and even more so in the presence of elevated fasting glucose. Our findings suggest a mutually potentiating effect of hyperglycemia and inflammation in cardiovascular risk prediction.
Single-Strand DNA-Binding Protein SSB1 Facilitates TERT Recruitment to Telomeres and Maintains Telomere G-Overhangs
Authors: Raj K. Pandita, Tracy T. Chow, Durga Udayakumar, Amanda L. Bain, Liza Cubeddu, Clayton R. Hunt, Wei Shi, Nobuo Horikoshi, Yong Zhao, Woodring E. Wright, Kum Kum Khanna, Jerry W. Shay, Tej K. Pandita
Journal: Cancer Research (2015)

Proliferating mammalian stem and cancer cells express telomerase [telomerase reverse transcriptase (TERT)] in an effort to extend chromosomal G-overhangs and maintain telomere ends. Telomerase-expressing cells also have higher levels of the single-stranded DNA-binding protein SSB1, which has a critical role in DNA double-strand break (DSB) repair. Here, we report that SSB1 binds specifically to G-strand telomeric DNA in vitro and associates with telomeres in vivo. SSB1 interacts with the TERT catalytic subunit and regulates its interaction with telomeres. Deletion of SSB1 reduces TERT interaction with telomeres and leads to G-overhang loss. Although SSB1 is recruited to DSB sites, we found no corresponding change in TERT levels at these sites, implying that SSB1-TERT interaction relies upon a specific chromatin structure or context. Our findings offer an explanation for how telomerase is recruited to telomeres to facilitate G-strand DNA extension, a critical step in maintaining telomere ends and cell viability in all cancer cells. Cancer Res; 75(5); 858-69. ©2015 AACR.
Symptoms of musculoskeletal disorders in stage rally drivers and co-drivers
Authors: N J Mansfield, J M Marshall
Journal: British Journal of Sports Medicine (2001)

During stage rallying, musculoskeletal injuries may be provoked by the high magnitude of vibration and shock to which the driver and co-driver are exposed. Drivers and co-drivers experience similar exposure to whole body mechanical shocks and vibration but different exposure to hand/wrist stressors.To investigate by a questionnaire study the prevalence of symptoms of musculoskeletal injuries after rallying in 13 professional and 105 amateur stage rally competitors.The self administered questionnaire investigated whole body and hand/wrist symptoms of musculoskeletal injury. It was loosely based on the Nordic design.91% of participants who competed or tested for more than 10 days a year (n=90) reported discomfort in at least one body area after rallying. Problems in the lumbar spine (70%), cervical spine (54%), shoulders (47%), and thoracic spine (36%) were the most common. There was a higher prevalence of cervical spine discomfort for co-drivers (62%) than for drivers (46%). Conversely, there was higher prevalence of discomfort in the hands and wrists for drivers (32%) than co-drivers (9%). The prevalence of low back pain in rally participants is higher than that generally reported for workers exposed to whole body vibration. The prevalence of discomfort in the hand and wrist for rally drivers is similar to that previously reported for Formula 1 drivers.Most stage rally drivers and co-drivers report symptoms of musculoskeletal injury. It is logical to relate the high prevalence of symptoms of injury to the extreme environment of the rally car.
C5a stimulates production of plasminogen activator inhibitor-1 in human mast cells and basophils
Authors: Johann Wojta, Christoph Kaun, Gerlinde Zorn, Minoo Ghannadan, Alexander W. Hauswirth, Wolfgang R. Sperr, Gerhard Fritsch, Dieter Printz, Bernd R. Binder, Georg Schatzl, Joerg Zwirner, Gerald Maurer, Kurt Huber, Peter Valent
Journal: Blood (2002)
The E3 ubiquitin-protein ligase Triad1 inhibits clonogenic growth of primary myeloid progenitor cells
Authors: Jurgen A.F. Marteijn, Liesbeth van Emst, Claudia A.J. Erpelinck-Verschueren, Gorica Nikoloski, Aswin Menke, Theo de Witte, Bob Löwenberg, Joop H. Jansen, Bert A. van der Reijden
Journal: Blood (2005)
LKB1/STK11 Suppresses Cyclooxygenase-2 Induction and Cellular Invasion through PEA3 in Lung Cancer
Authors: Sunil Upadhyay, Chunyan Liu, Aditi Chatterjee, Mohammad O. Hoque, Myoung Sook Kim, James Engles, William Westra, Barry Trink, Edward Ratovitski, David Sidransky
Journal: Cancer Research (2006)

Abstract We showed that the PEA3 transcriptional factor interacted with LKB1, a serine/threonine kinase, which is somatically mutated in lung cancer. This interaction occurred through the ETS domain of PEA3 and the kinase domain of LKB1. Mutation of LKB1 in lung cancer cells stabilized PEA3. Reintroduction of wild-type (WT) LKB1 into cells induced down-regulation of PEA3 and subsequently resulted in reduced cyclooxygenase-2 RNA and protein expression, whereas germ-line and somatic LKB1 mutants were defective in this activity. LKB1 phosphorylated PEA3 and promoted its degradation through a proteasome-mediated mechanism. Cells expressing mutant LKB1 possessed greater invasive potential compared with cells expressing WT LKB1. Increased invasion of cells with mutant LKB1 was partly due to PEA3 expression, as RNA interference inhibition of PEA3 resulted in dramatic decrease of Matrigel invasion. However, forced expression of PEA3 resulted in down-regulation of epithelial markers and induction of mesenchymal markers. These results suggest that PEA3 stabilization due to LKB1 inactivation could lead to epithelial/mesenchymal transition and greater lung cancer invasion potential. (Cancer Res 2006; 66(16): 7870-9)
Human Renal Cancer Cells Express a Novel Membrane-Bound Interleukin-15 that Induces, in Response to the Soluble Interleukin-15 Receptor α Chain, Epithelial-to-Mesenchymal Transition
Authors: Krystel Khawam, Julien Giron-Michel, Yanhong Gu, Aurélie Perier, Massimo Giuliani, Anne Caignard, Aurore Devocelle, Silvano Ferrini, Marina Fabbi, Bernard Charpentier, Andreas Ludwig, Salem Chouaib, Bruno Azzarone, Pierre Eid
Journal: Cancer Research (2009)

Abstract Although interleukin-15 (IL-15) is a powerful immunomodulatory factor that has been proposed for cancer immunotherapy, its intratumoral expression may be correlated with tumor progression and/or poor clinical outcome. Therefore, neoplasias potentially sensitive to immunotherapy should be checked for their IL-15 expression and function before choosing immunotherapy protocols. Primary human renal cancer cells (RCC) express a novel form of membrane-bound IL-15 (mb-IL-15), which displays three major original properties: (a) It is expressed as a functional membrane homodimer of 27 kDa, (b) it is shed in the extracellular environment by the metalloproteases ADAM17 and ADAM10, and (c) its stimulation by soluble IL-15 receptor α (s-IL-15Rα) chain triggers a complex reverse signal (mitogen-activated protein kinases, FAK, pMLC) necessary and sufficient to ~induce epithelial-mesenchymal transdifferentiation (EMT), a crucial process in tumor progression whose induction is unprecedented for IL-15. In these cells, complete EMT is characterized by a dynamic reorganization of the cytoskeleton with the subsequent generation of a mesenchymal/contractile phenotype (α-SMA and vimentin networks) and the loss of the epithelial markers E-cadherin and ZO-1. The retrosignaling functions are, however, hindered through an unprecedented cytokine/receptor interaction of mb-IL-15 with membrane-associated IL-15Rα subunit that tunes its signaling potential competing with low concentrations of the s-IL-15Rα chain. Thus, human RCC express an IL-15/IL-15R system, which displays unique biochemical and functional properties that seem to be directly involved in renal tumoral progression. [Cancer Res 2009;69(4):1561–9]
The neutrophilic leukocyte in wound repair
Authors: David M. Simpson, Russell Ross
Journal: Journal of Clinical Investigation (1972)

The role of the neutrophilic leukocyte in wound healing was investigated by observing the progress of repair in the absence of these cells. Circulating neutrophils were eliminated in guinea pigs by the administration of antineutrophil serum (ANS) 24 hr before wounding and by daily injections throughout a 10 day period of healing. Control animals received normal rabbit serum at the same dose levels and times. The wounds consisted of six linear incisions in the dorsal skin of the animals.The contents of 24-hr neutropenic and control wounds were compared by quantitating the major cellular and extracellular wound components using a histometric technique. At 24 hr, there were no differences between control and neutropenic wounds in the per cent of total wound volume occupied by mononuclear leukocytes and fibrin. The neutropenic wounds had no neutrophils, had a significantly decreased volume of fluid space, and an increased volume of red cells, as compared with controls. The differences in numbers of erythrocytes and amount of fluid space in these two sets of wounds may be related to substances within neutrophils that promote lysis of erythrocytes or affect vascular permeability. In spite of the lack of neutrophils in the ANS-treated animals during the 10 days of healing, no differences were observed between the control and neutropenic wounds relative to the rate of wound debridement or the extent of repair. The wounds from the two groups of animals were identical in cellularity and degree of connective tissue formation. These observations support the notion that neither wound debridement nor the formation of granulation tissue are dependent upon the presence of neutrophils. A neutrophil response in early wounds is not an essential antecedent to the infiltration of monocytes, as suggested by previous investigations.
Effective Gene Therapy of Biliary Tract Cancers by a Conditionally Replicative Adenovirus Expressing Uracil Phosphoribosyltransferase: Significance of Timing of 5-Fluorouracil Administration
Authors: Emiko Seo, Masato Abei, Mariko Wakayama, Kuniaki Fukuda, Hideyo Ugai, Takehide Murata, Takeshi Todoroki, Yasushi Matsuzaki, Naomi Tanaka, Hirofumi Hamada, Kazunari K. Yokoyama
Journal: Cancer Research (2005)

In order to enhance the efficacy of conditionally replicating adenoviruses (CRAd) in the treatment of cancers of the biliary tract, we studied the efficacy in vitro and in vivo of AxE1CAUP, a CRAd vector that carries a gene for uracil phosphoribosyltransferase (UPRT), which converts 5-fluorouracil (5-FU) directly to 5-fluorouridine monophosphate and greatly enhances the cytotoxicity of 5-FU. AxE1CAUP replicated and induced an increased UPRT expression in biliary cancer cells more efficiently than AxCAUP, a nonreplicative adenovirus carrying the UPRT gene. Whereas AxCAUP and AxE1AdB, a CRAd without the UPRT gene, modestly increased the sensitivity of BC cells to 5-FU, AxE1CAUP markedly increased the sensitivity, especially when the timing of 5-FU administration was appropriately chosen. AxE1CAUP replicated much less efficiently in normal WI-38 fibroblasts without any change in the sensitivity to 5-FU. In nude mice with s.c. biliary cancer xenografts, i.t. AxE1CAUP/5-FU therapy inhibited tumor growth significantly more strongly than AxCAUP/5-FU or AxE1AdB/5-FU therapy. Furthermore, in mice with peritoneally disseminated biliary cancer, i.p. AxE1CAUP efficiently proliferated in the tumors, decreased the tumor burden, and prolonged the survival of the mice when 5-FU was started 10 or 15 days after the vector inoculation, whereas earlier initiation of 5-FU resulted in early eradication of the vector and no survival benefit. The present study shows that the CRAd expressing UPRT was a more potent sensitizer of biliary cancer to 5-FU, than was a nonreplicative UPRT-encoding vector or a CRAd without UPRT gene, even at a lower dose of the vector, and that timing of 5-FU administration was a key factor to maximize the efficacy. This gene therapy with appropriately timed administration of 5-FU should be useful in overcoming the resistance of biliary cancers to 5-FU.
Assessment of alpha-1-antitrypsin deficiency heterozygosity as a risk factor in the etiology of emphysema. Physiological comparison of adult normal and heterozygous protease inhibitor phenotype subjects from a random population.
Authors: D J McDonagh, S P Nathan, R J Knudson, M D Lebowitz
Journal: Journal of Clinical Investigation (1979)

For plethysmographic studies of lung mechanics and measurement of pulmonary diffusing capacity, 62 subjects were drawn from a randomly selected population sample. Data obtained from the 24 subjects of heterozygous phenotype for alpha-1-antitrypsin deficiency (PiMZ) were compared by age group with data from 38 normal (PiM) subjects matched for sex, age, and smoking history. Comparison of mean values by age group for lung volumes, diffusing capacity, lung elastic recoil, maximum expiratory flow, and the occurrence of frequency dependence of dynamic compliance revealed no differences between phenotype groups. There was no evidence of an accelerated effect of aging among PiMZ subjects when compared with normal counterparts nor was there evidence of an increased effect of smoking. From these data it appears that the PiMZ phenotype per se is not a risk factor in the development of emphysema.
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Authors: Chung S Yang, Janelle M Landau, Mou-Tuan Huang, Harold L Newmark
Journal: Annual Review of Nutrition (2001)

▪ Abstract Plants consumed by humans contain thousands of phenolic compounds. The effects of dietary polyphenols are of great current interest due to their antioxidative and possible anticarcinogenic activities. A popular belief is that dietary polyphenols are anticarcinogens because they are antioxidants, but direct evidence for this supposition is lacking. This chapter reviews the inhibition of tumorigenesis by phenolic acids and derivatives, tea and catechins, isoflavones and soy preparations, quercetin and other flavonoids, resveratrol, and lignans as well as the mechanisms involved based on studies in vivo and in vitro. Polyphenols may inhibit carcinogenesis by affecting the molecular events in the initiation, promotion, and progression stages. Isoflavones and lignans may influence tumor formation by affecting estrogen-related activities. The bioavailability of the dietary polyphenols is discussed extensively, because the tissue levels of the effective compounds determine the biological activity. Understanding the bioavailability and blood and tissue levels of polyphenols is also important in extrapolating results from studies in cell lines to animal models and humans. Epidemiological studies concerning polyphenol consumption and human cancer risk suggest the protective effects of certain food items and polyphenols, but more studies are needed for clear-cut conclusions. Perspectives on the application of dietary polyphenols for the prevention of human cancer and possible concerns on the consumption of excessive amounts of polyphenols are discussed.
Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma
Authors: Tadeusz Robak, Huiqiang Huang, Jie Jin, Jun Zhu, Ting Liu, Olga Samoilova, Halyna Pylypenko, Gregor Verhoef, Noppadol Siritanaratkul, Evgenii Osmanov, Julia Alexeeva, Juliana Pereira, Johannes Drach, Jiri Mayer, Xiaonan Hong, Rumiko Okamoto, Lixia Pei, Brendan Rooney, Helgi van de Velde, Franco Cavalli
Journal: New England Journal of Medicine (2015)

The proteasome inhibitor bortezomib was initially approved for the treatment of relapsed mantle-cell lymphoma. We investigated whether substituting bortezomib for vincristine in frontline therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) could improve outcomes in patients with newly diagnosed mantle-cell lymphoma.In this phase 3 trial, we randomly assigned 487 adults with newly diagnosed mantle-cell lymphoma who were ineligible or not considered for stem-cell transplantation to receive six to eight 21-day cycles of R-CHOP intravenously on day 1 (with prednisone administered orally on days 1 to 5) or VR-CAP (R-CHOP regimen, but replacing vincristine with bortezomib at a dose of 1.3 mg per square meter of body-surface area on days 1, 4, 8, and 11). The primary end point was progression-free survival.After a median follow-up of 40 months, median progression-free survival (according to independent radiologic review) was 14.4 months in the R-CHOP group versus 24.7 months in the VR-CAP group (hazard ratio favoring the VR-CAP group, 0.63; P<0.001), a relative improvement of 59%. On the basis of investigator assessment, the median durations of progression-free survival were 16.1 months and 30.7 months, respectively (hazard ratio, 0.51; P<0.001), a relative improvement of 96%. Secondary end points were consistently improved in the VR-CAP group, including the complete response rate (42% vs. 53%), the median duration of complete response (18.0 months vs. 42.1 months), the median treatment-free interval (20.5 months vs. 40.6 months), and the 4-year overall survival rate (54% vs. 64%). Rates of neutropenia and thrombocytopenia were higher in the VR-CAP group.VR-CAP was more effective than R-CHOP in patients with newly diagnosed mantle-cell lymphoma but at the cost of increased hematologic toxicity. (Funded by Janssen Research and Development and Millennium Pharmaceuticals; LYM-3002 ClinicalTrials.gov number, NCT00722137.).
Outcome of delirium in critically ill patients: systematic review and meta-analysis
Authors: J. I. F. Salluh, H. Wang, E. B. Schneider, N. Nagaraja, G. Yenokyan, A. Damluji, R. B. Serafim, R. D. Stevens
Journal: BMJ (2015)

To determine the relation between delirium in critically ill patients and their outcomes in the short term (in the intensive care unit and in hospital) and after discharge from hospital.Systematic review and meta-analysis of published studies.PubMed, Embase, CINAHL, Cochrane Library, and PsychINFO, with no language restrictions, up to 1 January 2015.Reports were eligible for inclusion if they were prospective observational cohorts or clinical trials of adults in intensive care units who were assessed with a validated delirium screening or rating system, and if the association was measured between delirium and at least one of four clinical endpoints (death during admission, length of stay, duration of mechanical ventilation, and any outcome after hospital discharge). Studies were excluded if they primarily enrolled patients with a neurological disorder or patients admitted to intensive care after cardiac surgery or organ/tissue transplantation, or centered on sedation management or alcohol or substance withdrawal. Data were extracted on characteristics of studies, populations sampled, identification of delirium, and outcomes. Random effects models and meta-regression analyses were used to pool data from individual studies.Delirium was identified in 5280 of 16,595 (31.8%) critically ill patients reported in 42 studies. When compared with control patients without delirium, patients with delirium had significantly higher mortality during admission (risk ratio 2.19, 94% confidence interval 1.78 to 2.70; P<0.001) as well as longer durations of mechanical ventilation and lengths of stay in the intensive care unit and in hospital (standard mean differences 1.79 (95% confidence interval 0.31 to 3.27; P<0.001), 1.38 (0.99 to 1.77; P<0.001), and 0.97 (0.61 to 1.33; P<0.001), respectively). Available studies indicated an association between delirium and cognitive impairment after discharge.Nearly a third of patients admitted to an intensive care unit develop delirium, and these patients are at increased risk of dying during admission, longer stays in hospital, and cognitive impairment after discharge.
Delayed Expulsion of the Nematode <i>Trichinella spiralis</i>In Mice Lacking the Mucosal Mast Cell–Specific Granule Chymase, Mouse Mast Cell Protease-1
Authors: Pamela A. Knight, Steven H. Wright, Catherine E. Lawrence, Yvonne Y.W. Paterson, Hugh R.P. Miller
Journal: The Journal of Experimental Medicine (2000)

Expulsion of gastrointestinal nematodes is associated with pronounced mucosal mast cell (MMC) hyperplasia, differentiation, and activation, accompanied by the systemic release of MMC granule chymases (chymotrypsin-like serine proteases). The beta-chymase mouse mast cell protease-1 (mMCP-1) is expressed predominantly by intraepithelial MMCs, and levels in the bloodstream and intestinal lumen are maximal at the time of worm expulsion in parasitized mice. To address the in vivo functions of MMC-specific beta-chymases, we have generated transgenic mice that lack the mMCP-1 gene. They were backcrossed onto a congenic BALB/c background to investigate the response to nematode infection. The deletion of the mMCP-1 gene is associated with significantly delayed expulsion of Trichinella spiralis and increased deposition of muscle larvae in BALB/c mice despite the presence of normal and sometimes increased numbers of MMCs. Neither worm fecundity nor worm burdens were altered in Nippostrongylus-infected mMCP-1(-/)- BALB/c mice. These data demonstrate, for the first time, that the ablation of an MMC-derived effector molecule compromises the expulsion process.
(16) Kyrle's disease
Authors: R.S. Matthews
Journal: British Journal of Dermatology (1984)

Journal Article (16) Kyrle's disease Get access R.S. Matthews R.S. Matthews Waveney Hospital, Ballymena, County Antrim Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 111, Issue s26, 1 July 1984, Pages 62–63, https://doi.org/10.1111/j.1365-2133.1984.tb05286.x Published: 01 July 1984
Inhibitory effect of cimetidine on gastric acid secretion vagally activated by physiological means in duodenal ulcer patients.
Authors: I M Schoon, L Olbe
Journal: Gut (1978)

Vagal activation of gastric acid secretion by modified sham feeding in six patients with duodenal ulcer produced a peak acid response amounting to 52% of the peak acid output after pentagastrin stimulation (PAOpg). Cholinergic reflex stimulation of gastric acid secretion by fundic distension in another six patients with duodenal ulcer produced a peak acid response of 45% of PAOpg. Intravenous infusion of cimetidine in a dose of 100 mg/h markedly inhibited the acid sham feeding response by 90-100% and almost abolished the acid response to fundic distension. The results suggest that gastric acid secretion evoked by physiological vagal activation in man is profoundly inhibited by H2-receptor blocking agents.