tbuckley/cabot-search huggingface dataset:
Intravenous but not intragastric urogastrone-EGF is trophic to the intestine of parenterally fed rats.
Authors: R A Goodlad, T J Wilson, W Lenton, H Gregory, K G McCullagh, N A Wright
Journal: Gut (1987)

The effects of beta-urogastrone/human epidermal growth factor (URO-EGF) on intestinal epithelial cell proliferation were studied in rats in which intestinal cell proliferation had been reduced to a steady state basal level, by maintaining the rats on total parenteral nutrition. The accumulation of arrested metaphases over a two hour time period was determined in a dose response study. Increasing doses of URO-EGF progressively raised the two hour collection of metaphases and intestinal weights. Intravenous infusion of URO-EGF was also effective in restoring cell proliferation when it was infused after the intestine had become hypoproliferative. beta-urogastrone/human epidermal growth factor administered through an intragastric cannulae thrice daily had no significant effect on intestinal weight or crypt cell production rate or metaphase collection. It is proposed that one of the in vivo actions of urogastrone-epidermal growth factor is the maintenance of gastrointestinal growth and that this occurs through a systemic rather than a luminal mechanism.
Prevalence and intensity of rhinoconjunctivitis in subjects with occupational asthma
Authors: JL Malo, C Lemiere, A Desjardins, A Cartier
Journal: European Respiratory Journal (1997)

Subjects with occupational asthma may also report symptoms of rhinoconjunctivitis. The aims of this study were: 1) to assess the prevalence of rhinoconjunctivitis in association with occupational asthma, and the severity of rhinoconjunctivitis according to the type of agent (high (HMW) and low (LMW) molecular weight agents) causing occupational asthma; and 2) to evaluate the timing of occurrence of symptoms of rhinoconjunctivitis in relation to those of occupational asthma. A questionnaire on symptoms of rhinoconjunctivitis and its timing in relation to the development of chest symptoms was prospectively addressed to 143 subjects consecutively referred to an occupational asthma clinic. Objective testing through specific inhalation challenges confirmed the diagnosis of occupational asthma in 40 subjects. Symptoms of rhinitis were reported at some time by 37 of the 40 subjects (92%), and of conjunctivitis by 29 of the 40 subjects (72%). The prevalence of symptoms was not different for HMW and LMW agents, although rhinitis was more intense for HMW (19 out of 24 subjects with three or more of the following symptoms: runny nose, itchy nose, nasal blockage, and sneezing) than for LMW (5 out of 14 subjects) (p&lt;0.01). There were significantly fewer subjects with occupational asthma due to LMW agents, with rhinitis appearing before asthma (p=0.03). Figures for conjunctivitis showed a similar trend, but did not reach statistical significance. In conclusion, symptoms of rhinoconjunctivitis are often associated with occupational asthma. Rhinitis is less pronounced in the case of low molecular weight agents, but more often appears before occupational asthma in the case of high molecular weight agents.
NF-κB-EGFR cross talk in lung cell proliferation
Authors: Arindam Bhattacharyya
Journal: European Respiratory Journal (2014)

The role of cadmium with respect to cell growth is still under debate. Low concentration of cadmium was applied to mice primary lung epithelial cells and cell proliferation was measured both by cell cycle analysis and Brdu incorporation assay, effects of different dose of cadmium on lung epithelial cells was evaluated morphologically by atomic force microscopy. RT-PCR and western blot confirmed the specific signalling pathways regarding cadmium induced lung cell proliferation. Primary lung epithelial cells were transfected with siEGFR and molecular interactions of downstream signalling molecules were determined. We have reported RNAi induced silencing of the EGFR, which is over expressed in cadmium induced primary mouse lung epithelial cells. siEGFR effectively prevents expression of proinflammatory and cell proliferative markers. Moreover N-acetyl cysteine mediated inhibition of EGFR and downstream signalling molecules indicate the involvement of reactive oxygen species induced up regulation of EGFR by lower dose of cadmium. We have evaluated how exposure to low concentration of cadmium promotes the growth of primary mice lung epithelial cell by EGFR signalling. We have also transfected the primary lung epithelial cell with siRNA against the regulatory subunit of nuclear factor κβ (NF-κβ) and the data shows that cadmium induced lung cell proliferation is the effect of EGFR mediated NF-κβ activation.
Government drops original pledge to boost physical exercise
Authors: A. O'Dowd
Journal: BMJ (2011)

The coalition government has dropped a pledge made by its predecessor to increase general physical activity among the population despite the aims of its public health white paper.

In an interview published in the Guardian newspaper, Olympics secretary Jeremy Hunt admitted that targets on exercise and sport created by the previous Labour government as a response to winning the bid to host the 2012 Olympics in London, have been dropped or are uncertain to continue.

The Department for Culture, Media and Sport, however, has stressed that it is looking at better ways to encourage more participation in sport and exercise.

Mr Hunt said the pledge—promising to get a million more people …
Arsenic trioxide and ascorbic acid interfere with the BCL2 family genes in patients with myelodysplastic syndromes: an ex-vivo study
Authors: Sara Galimberti, Francesca Guerrini, Flavia Salvi, Iacopo Petrini, Daniela Gioia, Emanuela Messa, Giuseppe A Palumbo, Daniela Cilloni, Mario Petrini, Alessandro Levis
Journal: Journal of Hematology & Oncology (2012)

Arsenic Trioxide (ATO) is effective in about 20% of patients with myelodysplasia (MDS); its mechanisms of action have already been evaluated in vitro, but the in vivo activity is still not fully understood. Since ATO induces apoptosis in in vitro models, we compared the expression of 93 apoptotic genes in patients' bone marrow before and after ATO treatment. For this analysis, we selected 12 patients affected by MDS who received ATO in combination with Ascorbic Acid in the context of the Italian clinical trial NCT00803530, EudracT Number 2005-001321-28. Real-time PCR quantitative assays for genes involved in apoptosis were performed using TaqMan® Assays in 384-Well Microfluidic Cards "TaqMan® Human Apoptosis Array". Quantitative RT-PCR for expression of EVI1 and WT1 genes was also performed. Gene expression values (Ct) were normalized to the median expression of 3 housekeeping genes present in the card (18S, ACTB and GAPDH). ATO treatment induced up-regulation of some pro-apoptotic genes, such as HRK, BAK1, CASPASE-5, BAD, TNFRSF1A, and BCL2L14 and down-regulation of ICEBERG. In the majority of cases with stable disease, apoptotic gene expression profile did not change, whereas in cases with advanced MDS more frequently pro-apoptotic genes were up-regulated. Two patients achieved a major response: in the patient with refractory anemia the treatment down-regulated 69% of the pro-apoptotic genes, whereas 91% of the pro-apoptotic genes were up-regulated in the patient affected by refractory anemia with excess of blasts-1. Responsive patients showed a higher induction of BAD than those with stable disease. Finally, WT1 gene expression was down-regulated by the treatment in responsive cases. These results represent the basis for a possible association of ATO with other biological compounds able to modify the apoptotic pathways, such as inhibitors of the BCL2 family.
The Amino Acid Sequence of a Major Nonimmunoglobulin Component of Some Amyloid Fibrils
Authors: Mark Levin, Edward C. Franklin, Blas Frangione, Mordechai Pras
Journal: Journal of Clinical Investigation (1972)

The complete amino acid sequence of a protein, acid soluble fraction, (ASF) which constitutes up to 50% of amyloid fibrils from a patient with familial Mediterranean fever has been obtained. Partial amino acid sequences of three other proteins from patients with secondary amyloidosis were identical in the regions studied except for an alanine-valine interchange in one. The ASF contains no cysteine, does not resemble any known immunoglobulin, and has not been detected as yet in myeloma-associated amyloid.
Karyotyping, congenital anomalies and follow-up of children after intracytoplasmic sperm injection with non-ejaculated sperm: a systematic review
Authors: G.H. Woldringh, D.E. Besselink, A.H.J. Tillema, J.C.M. Hendriks, J.A.M. Kremer
Journal: Human Reproduction Update (2009)

For men with azoospermia, it is possible to father their own progeny by intracytoplasmic sperm injection (ICSI) with epididymal or testicular sperm. Some studies show that children born after assisted reproductive technology (ART) are at increased risk of birth defects, other studies suggest that there is no extra concern about ICSI children conceived with epididymal or testicular sperm.Studies about the karyotypes of fetuses, congenital anomalies and the follow-up of the children born after ICSI with non-ejaculated sperm were identified by means of a systematic literature search.Eight relevant studies were identified; two studies reported karyotype, five reported malformations and one reported follow-up of children after ICSI. In total, there were 55 out of 1973 (2.8%) abnormal karyotypes in the ICSI with ejaculated sperm group, 0 out of 31 in the ICSI with epididymal sperm group and 5 out of 191 (2.6%) in the ICSI with testicular sperm group. Major malformations were found in 543 out of 12 377 (4.4%) in the ICSI with ejaculated sperm group, 17 out of 533 (3.2%) in the ICSI with epididymal sperm group and 31 out of 670 (4.6%) in the ICSI with testicular sperm group.Although there were no statistical differences, the study groups were small and heterogenic, with a number of potential biases. We therefore recommend a standardized methodology of follow-up studies after ART, with well-defined groups of ICSI with ejaculated sperm, ICSI with epididymal sperm and ICSI with testicular sperm, and a control group of naturally conceived children.
Protective role of IgA1 glycans against IgA1 self-aggregation and adhesion to extracellular matrix proteins.
Authors: T Kokubo, Y Hiki, H Iwase, A Tanaka, K Toma, K Hotta, Y Kobayashi
Journal: Journal of the American Society of Nephrology (1998)

The aim of this study was to investigate the role of carbohydrate moieties attached to IgA1 hinge region in IgA1 self-aggregation and adhesion to extracellular matrix (ECM) proteins previously reported in IgA nephropathy. Serum IgA1 samples isolated from healthy individuals were digested with neuraminidase (NA), NA + beta-galactosidase, and NA + beta-galactosidase + alpha-N-acetylgalactosaminidase to remove the carbohydrates from the hinge region and were named asialo, agalacto, and naked IgA1, respectively. First, polyacrylamide gel electrophoresis was performed under the native condition, and consequently, a broad band indicating IgA1 self-aggregation was clearly observed in asialo, agalacto, and naked IgA1, but not in native IgA1. However, the broad band disappeared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under the nonreducing condition. Second, it was shown that IgA1 adhesion activities to type IV collagen, fibronectin, and laminin were significantly higher in asialo, agalacto, and naked IgA1 than in native IgA1, using enzyme-linked immunosorbent assay (asialo, agalacto, and naked versus native: P < 0.01). In addition, agalacto IgA1 had the highest affinity for all of the ECM proteins among the deglycosylated IgA1 (agalacto versus asialo and naked, P < 0.05). These results indicated that the removal of carbohydrates from the IgA1 molecule resulted in noncovalent self-aggregation and a significant increase in adhesion to the ECM proteins. It was therefore suggested that the IgA1 glycans played a protective role against aggregation and adhesion and that the underglycosylation of the IgA1 molecule found in IgA nephropathy could be involved in the nonimmunologic glomerular accumulation of IgA1.
Mechanoreflex Mediates the Exaggerated Exercise Pressor Reflex in Heart Failure
Authors: Scott A. Smith, Jere H. Mitchell, R. Haris Naseem, Mary G. Garry
Journal: Circulation (2005)

Background— In heart failure, exercise elicits excessive increases in mean arterial pressure (MAP) and heart rate (HR). Using a novel rat model, we previously demonstrated that this exaggerated cardiovascular responsiveness is mediated by an overactive exercise pressor reflex (EPR). Although we previously determined that abnormalities in the group IV afferent neuron population (associated with the metabolic component of the reflex) initiate the development of the exaggerated EPR in heart failure, these fibers do not mediate the enhanced circulatory responses to exercise. Therefore, we hypothesized that the augmentation in EPR activity is primarily mediated by the mechanically sensitive component of the reflex (mediated predominately by activation of group III afferent fibers). Methods and Results— Male Sprague-Dawley rats were divided into 3 groups: sham (control), dilated cardiomyopathic (DCM), and neonatal capsaicin-treated animals (NNCAP, group IV afferent fibers ablated). Activation of the EPR by electrically induced static muscle contraction of the hindlimb resulted in larger increases in MAP and HR in DCM and NNCAP compared with sham animals. In all groups, administration of gadolinium (a selective blocker of mechanically sensitive receptors) within the hindlimb attenuated the MAP and HR responses to contraction. However, the magnitude of this reduction was greater in DCM and NNCAP compared with sham animals. Conclusions— From these data, we conclude that the muscle mechanoreflex mediates the exaggerated EPR that develops in heart failure. Moreover, these findings suggest that mechanoreflex overactivity in heart failure may be a compensatory response to functional alterations in group IV fibers. Given these findings, the muscle mechanoreflex may serve as a novel target in the treatment of the abnormal circulatory responses to exercise in heart failure.
Does the death knell toll for phlebotomy in NAFLD?
Authors: John D. Ryan, Thomas Marjot, Jeremy F. Cobbold
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. To the Editor: Adams et al. describe the second randomized trial examining the impact of iron reduction therapy by phlebotomy in nonalcoholic fatty liver disease (NAFLD).1 Despite a significant reduction in serum ferritin, no improvement in steatosis, disease markers, or insulin resistance was noted in the treatment group. The researchers suggest that benefits observed in previous smaller, nonrandomized trials were influenced by bias. Could the lack of effect observed in the present study relate to the study inclusion criteria? Iron reduction as a potential treatment for NAFLD and metabolic syndrome is based on observational data and numerous molecular studies implicating iron excess in the development of insulin resistance and liver injury. Moreover, several studies suggest a benefit of venesection in diabetes and NAFLD patients.2 The researchers deserve credit for their efforts in executing this well‐conducted trial, but several factors limit the ability of this study to assess the effect of iron reduction therapy. A lack of histological assessment before and after treatment limits patient stratification and assessment of response. Unlike a previous controlled trial showing benefit of venesection in reducing the NAFLD Activity Score,3 there was a much lower prevalence of probable NASH or significant fibrosis in this study. Indeed, mean Hepascore values in both study arms were less than the previously reported cutoff of 0.44 for significant fibrosis (Kleiner fibrosis grade ≥2), whereas, similarly, mean cytokeratin 18 fragment levels were lower than that (275 U/L) suggested to indicate NASH.4 Baseline hepatic iron concentration (HIC) values for both patient groups were within normal limits, indicating a lack of iron excess in the study population. Furthermore, the proportion of patients successfully reaching target ferritin levels after treatment is unclear; and though HIC, as measured by magnetic resonance imaging, appears reduced in the treatment cohort, statistical significance is not described. These are important caveats, given that patients with established NASH, evidence of iron overload, and insulin resistance are those in whom a demonstrable effect of iron reduction therapy might be expected. So, although this study represents an important addition to the field of iron and NAFLD research, it may be premature to sound the death knell for phlebotomy as a treatment approach for this condition.
Lifestyle Change and Mobility in Obese Adults with Type 2 Diabetes
Authors: W. Jack Rejeski, Edward H. Ip, Alain G. Bertoni, George A. Bray, Gina Evans, Edward W. Gregg, Qiang Zhang
Journal: New England Journal of Medicine (2012)

Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients.We randomly assigned 5145 overweight or obese adults between the ages of 45 and 74 years with type 2 diabetes to either an intensive lifestyle intervention or a diabetes support-and-education program; 5016 participants contributed data. We used hidden Markov models to characterize disability states and mixed-effects ordinal logistic regression to estimate the probability of functional decline. The primary outcome was self-reported limitation in mobility, with annual assessments for 4 years.At year 4, among 2514 adults in the lifestyle-intervention group, 517 (20.6%) had severe disability and 969 (38.5%) had good mobility; the numbers among 2502 participants in the support group were 656 (26.2%) and 798 (31.9%), respectively. The lifestyle-intervention group had a relative reduction of 48% in the risk of loss of mobility, as compared with the support group (odds ratio, 0.52; 95% confidence interval, 0.44 to 0.63; P<0.001). Both weight loss and improved fitness (as assessed on treadmill testing) were significant mediators of this effect (P<0.001 for both variables). Adverse events that were related to the lifestyle intervention included a slightly higher frequency of musculoskeletal symptoms at year 1.Weight loss and improved fitness slowed the decline in mobility in overweight adults with type 2 diabetes. (Funded by the Department of Health and Human Services and others; ClinicalTrials.gov number, NCT00017953.).
Systemic Blockade of Transforming Growth Factor-β Signaling Augments the Efficacy of Immunogene Therapy
Authors: Samuel Kim, George Buchlis, Zvi G. Fridlender, Jing Sun, Veena Kapoor, Guanjun Cheng, Andrew Haas, Hung Kam Cheung, Xiamei Zhang, Michael Corbley, Larry R. Kaiser, Leona Ling, Steven M. Albelda
Journal: Cancer Research (2008)

Abstract Locally produced transforming growth factor-β (TGF-β) promotes tumor-induced immunosuppression and contributes to resistance to immunotherapy. This article explores the potential for increased efficacy when combining immunotherapies with TGF-β suppression using the TGF-β type I receptor kinase inhibitor SM16. Adenovirus expressing IFN-β (Ad.IFN-β) was injected intratumorally once in established s.c. AB12 (mesothelioma) and LKR (lung cancer) tumors or intratracheally in a Kras orthotopic lung tumor model. Mice bearing TC1 (lung cancer) tumors were vaccinated with two injections of adenovirus expressing human papillomavirus-E7 (HPV-E7; Ad.E7). SM16 was administered orally in formulated chow. Tumor growth was assessed and cytokine expression and cell populations were measured in tumors and spleens by real-time PCR and flow cytometry. SM16 potentiated the efficacy of both immunotherapies in each of the models and caused changes in the tumor microenvironment. The combination of SM16 and Ad.IFN-β increased the number of intratumoral leukocytes (including macrophages, natural killer cells, and CD8+ cells) and increased the percentage of T cells expressing the activation marker CD25. SM16 also augmented the antitumor effects of Ad.E7 in the TC1 flank tumor model. The combination did not increase HPV-E7 tetramer-positive CD8+ T cells in the spleens but did induce a marked increase in the tumors. Tumors from SM16-treated mice showed increased mRNA and protein for immunostimulatory cytokines and chemokines, as well as endothelial adhesion molecules, suggesting a mechanism for the increased intratumoral leukocyte trafficking. Blockade of the TGF-β signaling pathway augments the antitumor effects of Ad.IFN-β immune-activating or Ad.E7 vaccination therapy. The addition of TGF-β blocking agents in clinical trials of immunotherapies may increase efficacy. [Cancer Res 2008;68(24):10247–56
Fish Oil for the Reduction of Atrial Fibrillation Recurrence, Inflammation, and Oxidative Stress
Authors: Anil Nigam, Mario Talajic, Denis Roy, Stanley Nattel, Jean Lambert, Anna Nozza, Peter Jones, Vanu R. Ramprasath, Gilles O’Hara, Stephen Kopecky, James M. Brophy, Jean-Claude Tardif
Journal: Journal of the American College of Cardiology (2014)
Resveratrol Promotes Autophagic Cell Death in Chronic Myelogenous Leukemia Cells via JNK-Mediated p62/SQSTM1 Expression and AMPK Activation
Authors: Alexandre Puissant, Guillaume Robert, Nina Fenouille, Frederic Luciano, Jill-Patrice Cassuto, Sophie Raynaud, Patrick Auberger
Journal: Cancer Research (2010)

Autophagy that is induced by starvation or cellular stress can enable cancer cell survival by sustaining energy homeostasis and eliminating damaged organelles and proteins. In response to stress, cancer cells have been reported to accumulate the protein p62/SQSTM1 (p62), but its role in the regulation of autophagy is controversial. Here, we report that the plant phytoalexin resveratrol (RSV) triggers autophagy in imatinib-sensitive and imatinib-resistant chronic myelogenous leukemia (CML) cells via JNK-dependent accumulation of p62. JNK inhibition or p62 knockdown prevented RSV-mediated autophagy and antileukemic effects. RSV also stimulated AMPK, thereby inhibiting the mTOR pathway. AMPK knockdown or mTOR overexpression impaired RSV-induced autophagy but not JNK activation. Lastly, p62 expression and autophagy in CD34+ progenitors from patients with CML was induced by RSV, and disrupting autophagy protected CD34+ CML cells from RSV-mediated cell death. We concluded that RSV triggered autophagic cell death in CML cells via both JNK-mediated p62 overexpression and AMPK activation. Our findings show that the JNK and AMPK pathways can cooperate to eliminate CML cells via autophagy.