tbuckley/cabot-search huggingface dataset:
Effect of fasting, hypocaloric feeding, and refeeding on the energetics of stimulated rat muscle as assessed by nuclear magnetic resonance spectroscopy.
Authors: A Mijan de la Torre, A Madapallimattam, A Cross, R L Armstrong, K N Jeejeebhoy
Journal: Journal of Clinical Investigation (1993)

A previous study suggested that muscles from hypocalorically fed rats were limited in their ability to rephosphorylate ADP. During muscle contraction hydrolysis of ATP results in an increase in phosphorus, free ADP, delta GATP, and a reduction in phosphocreatine levels that is reversed during rest by rephosphorylation of ADP to ATP and the resynthesis of phosphocreatine by ATP. We therefore hypothesized that these changes would be restored more slowly during postcontraction rest in hypocalorically fed rats as compared with controls. We compared controls fed ad lib to 2-d fasted and hypocalorically fed rats, losing 20% of their weight. We also compared hypocalorically fed rats that had been refed ad lib for 7 d with age-matched controls fed ad lib. The results showed that ATP, muscle pH, and total muscle creatine levels were not different in all groups. The raised phosphorus and delta GATP levels and lower phosphocreatine/phosphorus ratio at the end of contraction changed more slowly during rest in the hypocaloric rats. These abnormalities were partially corrected by refeeding. The data taken as a whole support the concept of impaired rephosphorylation of ADP in malnourished muscle that is not completely restored by refeeding in stimulated muscle.
Dopamine mediates vagal modulation of the immune system by electroacupuncture
Authors: Rafael Torres-Rosas, Ghassan Yehia, Geber Peña, Priya Mishra, Maria del Rocio Thompson-Bonilla, Mario Adán Moreno-Eutimio, Lourdes Andrea Arriaga-Pizano, Armando Isibasi, Luis Ulloa
Journal: Nature Medicine (2014)
Bile acid sequestrants improve glycemic control in type 2 diabetes: A proposed mechanism implicating glucagon-like peptide 1 release
Authors: Alan F. Hofmann
Journal: Hepatology (2010)

In HEPATOLOGY, Brufau et al.1 recently reported their examination of the effect of colesevelam, a potent bile acid sequestrant, on glycemic control and bile acid kinetics in patients with type 2 diabetes. Colesevelam improved glycemic parameters and caused the expected increase in cholic acid synthesis. However, the authors "found no correlation between markers of insulin resistance/glucose metabolism and bile acid metabolism," and they concluded that a firm link between bile acid and glucose metabolism in type 2 diabetes mellitus remained elusive. The purpose of this note is to propose a mechanism by which colesevelam improves glycemic control in patients with type 2 diabetes. The mechanism is increased release of glucagon-like peptide 1 (GLP-1) from the L cells of the ileum. This GLP-1 release is induced by fatty acids that reach the ileum because of defective micellar solubilization in the jejunum. In a healthy person, fatty acids are generated by pancreatic lipases acting at the triglyceride/water interface. Fatty acids are solubilized in mixed micelles with conjugated bile acids. Normally, fatty acid absorption is remarkably efficient and complete by the proximal jejunum. When a bile acid sequestrant is administered, it binds bile acids, removes them from solution, and decreases the fatty acid concentration in the aqueous phase.2 Fatty acids that are not solubilized in micelles can be absorbed by the diffusion of individual molecules through the aqueous boundary layer, but this is a slow process. Fatty acids will remain in an emulsified form; experimentally, absorption from an emulsion is slower than absorption from a micellar solution.3 As a result, fatty acids will pass into the ileum, where they will enter L cells and stimulate GLP-1 release. In rats, biliary diversion changes the site of fatty acid absorption from predominantly the jejunum to both the jejunum and the ileum.4 This proposed mechanism can also explain why intestinal transposition or anti-obesity operations that cause fatty acids to reach the ileum improve type 2 diabetes. This proposed mechanism does not exclude substances in plasma such as cholecystokinin5 or bile acid derivatives6 acting on L cells from the basolateral side and evoking GLP-1 release. Alan F. Hofmann M.D.*, * Department of Medicine, University of California, San Diego, CA.
Evaluation of a new reactive solid phase for radioimmunoassay of serum specific IgE against muscle relaxant drugs
Authors: J. L. GUEANT, E. MATA, B. MONIN, D. A. MONERET‐VAUTRIN, L. KAMEL, J. P. NICOLAS, M. C. LAXENAIRE
Journal: Allergy (1991)

Until now, immunoassays for detection of anti‐muscle relaxant IgE in serum have been performed with the drug coupled to epoxy‐activated Sepharose or to RAST papers dics. In the present work we have used a quaternary ammonium‐Sepharose in which the quaternary ammonium reactive group (choline chloride) was directly coupled to Sepharose via an ether linkage. 50 μl of the quaternary ammonium solid phase (QAS) was incubated with 50 μl of serum for 3 h, washed, incubated 18 h with 125 I‐anti‐IgE and washed again. The results were expressed as the percentage of 125 I‐anti‐IgE adsorbed onto the solid phase. The results were at 1.3±0.5% for 20 control sera, with an upper normal limit estimated to 2.3%. The within‐run reproducibility ranged from 3.2% to 10.0%. The results were significantly correlated with those obtained with either alcuronium‐epoxy‐Sepharose, choline‐epoxy‐Sepharose, the RAST‐alcuronium or with the RAST‐succinyl choline (respectively, r ‐ 0.66, r = 0.80, r = 0.81, r = 0.40 and r = 0.85). The values obtained with the sera of 83 patients ranged from 0.3 to 38.5%. The sensitivity was estimated at 87.9%, 66.7% and 40.7% with the QAS‐RIA, the RAST‐succinyl choline and the RAST‐alcuronium, respectively. The inhibition of adsorption of specific IgE onto the gel ranged from 13.0 to 90.6% in presence of 130 nmol of soluble muscle relaxants. In 83.3% of 30 cases, the highest inhibition was obtained with the muscle relaxant which was clinically incriminated. In conclusion, the reactive‐solid phase which was used in the present work significantly increased the sensitivity of detection of anti‐muscle relaxant IgE in serum.
Spectrum and Short-term Outcome of Renal Impairment in Cirrhosis
Authors: S. Vinit, A. Kumar, P. Sharma, R. Bansal, P. Tyagi, N. Bansal, V. Singla, M. Kumar, P. Ranjan, M. Sachdeva, A. Arora
Journal: Clinical Gastroenterology and Hepatology (2015)
Oncogenic hypophosphataemic osteomalacia mimicking bone metastases on isotope bone scan
Authors: J K Dowman, F H Khattak
Journal: Annals of the Rheumatic Diseases (2006)

A 61-year-old man presented with an 18-month history of musculoskeletal pain affecting the dorsolumbar spine, ribs and thighs, and a 6-month history of pain and swelling of the left foot. Examination showed rib tenderness, and mild swelling and tenderness of the left foot. The only abnormality detected on initial investigations was a raised alkaline phosphatase of level 266 U/l (normal range 37–170 U/l). Plain radiographs of the lumbar spine and foot were normal, but an isotope bone scan showed extensive hot spots in the left foot and in the ribs bilaterally, which were highly suggestive …
Fixed versus flexible strategists: Individual differences in facultative responsiveness?
Authors: Jay Belsky
Journal: Behavioral and Brain Sciences (2000)

Gangestad &amp; Simpson's central premise regarding individual differences is applied to their facultative-argument based on mating- strategy, for individual differences in susceptibility to contextual effects. Some individuals may be relatively fixed strategists who are rather unresponsive to context when it comes to mating, whereas others, perhaps most, may be, as G&amp;S propose, flexible strategists.
Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits
Authors: Jennifer Glass, Krista L Lanctôt, Nathan Herrmann, Beth A Sproule, Usoa E Busto
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To quantify and compare potential benefits (subjective reports of sleep variables) and risks (adverse events and morning-after psychomotor impairment) of short term treatment with sedative hypnotics in older people with insomnia. <b>Data sources</b> Medline, Embase, the Cochrane clinical trials database, PubMed, and PsychLit, 1966 to 2003; bibliographies of published reviews and meta-analyses; manufacturers of newer sedative hypnotics (zaleplon, zolpidem, zopiclone) regarding unpublished studies. <b>Selection criteria</b> Randomised controlled trials of any pharmacological treatment for insomnia for at least five consecutive nights in people aged 60 or over with insomnia and otherwise free of psychiatric or psychological disorders. <b>Results</b> 24 studies (involving 2417 participants) with extractable data met inclusion and exclusion criteria. Sleep quality improved (effect size 0.14, P &lt; 0.05), total sleep time increased (mean 25.2 minutes, P &lt; 0.001), and the number of night time awakenings decreased (0.63, P &lt; 0.001) with sedative use compared with placebo. Adverse events were more common with sedatives than with placebo: adverse cognitive events were 4.78 times more common (95% confidence interval 1.47 to 15.47, P &lt; 0.01); adverse psychomotor events were 2.61 times more common (1.12 to 6.09, P &gt; 0.05), and reports of daytime fatigue were 3.82 times more common (1.88 to 7.80, P &lt; 0.001) in people using any sedative compared with placebo. <b>Conclusions</b> Improvements in sleep with sedative use are statistically significant, but the magnitude of effect is small. The increased risk of adverse events is statistically significant and potentially clinically relevant in older people at risk of falls and cognitive impairment. In people over 60, the benefits of these drugs may not justify the increased risk, particularly if the patient has additional risk factors for cognitive or psychomotor adverse events.
Anion Exchanger 1 Interacts with Nephrin in Podocytes
Authors: Fiona Wu, Moin A. Saleem, Nicole B. Kampik, Timothy J. Satchwell, Rosalind C. Williamson, Simone M. Blattner, Lan Ni, Tibor Toth, Graham White, Mark T. Young, Mark D. Parker, Seth L. Alper, Carsten A. Wagner, Ashley M. Toye
Journal: Journal of the American Society of Nephrology (2010)

The central role of the multifunctional protein nephrin within the macromolecular complex forming the glomerular slit diaphragm is well established, but the mechanisms linking the slit diaphragm to the cytoskeleton and to the signaling pathways involved in maintaining the integrity of the glomerular filter remain incompletely understood. Here, we report that nephrin interacts with the bicarbonate/chloride transporter kidney anion exchanger 1 (kAE1), detected by yeast two-hybrid assay and confirmed by immunoprecipitation and co-localization studies. We confirmed low-level glomerular expression of kAE1 in human and mouse kidneys by immunoblotting and immunofluorescence microscopy. We observed less kAE1 in human glomeruli homozygous for the NPHS1(FinMaj) nephrin mutation, whereas kAE1 expression remained unchanged in the collecting duct. We could not detect endogenous kAE1 expression in NPHS1(FinMaj) podocytes in primary culture, but heterologous re-introduction of wild-type nephrin into these podocytes rescued kAE1 expression. In kidneys of Ae1(-/-) mice, nephrin abundance was normal but its distribution was altered along with the reported kAE1-binding protein integrin-linked kinase (ILK). Ae1(-/-) mice had increased albuminuria with glomerular enlargement, mesangial expansion, mesangiosclerosis, and expansion of the glomerular basement membrane. Glomeruli with ILK-deficient podocytes also demonstrated altered AE1 and nephrin expression, further supporting the functional interdependence of these proteins. These data suggest that the podocyte protein kAE1 interacts with nephrin and ILK to maintain the structure and function of the glomerular basement membrane.
Can metacognition be explained in terms of perceptual symbol systems?
Authors: Ruediger Oehlmann
Journal: Behavioral and Brain Sciences (1999)

Barsalou's theory of perceptual symbol systems is considered from a metacognitive perspective. Two examples are discussed in terms of the proposed perceptual symbol theory. First, recent results in research on feeling-of-knowing judgement are used to argue for a representation of familiarity with input cues. This representation should support implicit memory. Second, the ability of maintaining a theory of other people's beliefs (theory of mind) is considered and it is suggested that a purely simulation-based view is insufficient to explain the available evidence. Both examples characterize areas where Barsalou's theory would benefit from additional detail.
Activity of Suberoylanilide Hydroxamic Acid Against Human Breast Cancer Cells with Amplification of Her-2
Authors: Purva Bali, Michael Pranpat, Ramona Swaby, Warren Fiskus, Hirohito Yamaguchi, Maria Balasis, Kathy Rocha, Hong-Gang Wang, Victoria Richon, Kapil Bhalla
Journal: Clinical Cancer Research (2005)

We determined the effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on hsp90 and its client proteins Her-2, AKT, and c-Raf, as well as evaluated the cytotoxic effects of co-treatment of SAHA with trastuzumab or docetaxel in human breast cancer BT-474 and SKBR-3 cells containing amplification of Her-2.The cells were treated with SAHA (1.0-5.0 micromol/L) and/or trastuzumab (5-40 microg/mL) or docetaxel (5-20 nmol/L). Following this, apoptosis and the levels of p21(WAF1), p27(KIP1), AKT, c-Raf, and Her-2, as well as of the key regulators of apoptosis were determined. Synergistic interaction between drugs was evaluated by median dose-effect analysis.Treatment with SAHA up-regulated p21(WAF1) and p27(KIP1) levels, increased the percentage of cells in G2-M phase of the cell cycle, as well as induced apoptosis in a dose-dependent manner. This was associated with up-regulation of the pro-death Bak and Bim, as well as with attenuation of the levels of Her-2 and XIAP, survivin, Bcl-2, and Bcl-x(L) proteins. SAHA treatment induced acetylation of hsp90. This reduced the chaperone association of Her-2 with hsp90, promoting polyubiquitylation and degradation of Her-2. SAHA also attenuated the levels of c-Raf and AKT. Co-treatment with SAHA significantly increased trastuzumab or docetaxel-induced apoptosis of BT-474 and SKBR-3 cells. Additionally, median dose-effect analysis revealed that co-treatment with SAHA and trastuzumab or docetaxel induced synergistic cytotoxic effects against the breast cancer cells.These preclinical findings support the development of SAHA in combination with docetaxel and/or trastuzumab against Her-2-amplified breast cancer.
Therapeutic opportunities in systemic lupus erythematosus: state of the art and prospects for the new decade
Authors: G. K. Bertsias, J. E. Salmon, D. T. Boumpas
Journal: Annals of the Rheumatic Diseases (2010)

Immune responses against endogenous nuclear antigens are characteristic of systemic lupus erythematosus (SLE), a highly pleiomorphic disease predominantly affecting young women of reproductive age. Genome-wide association studies have confirmed the importance of genes associated with the immune response as well as genes involved in endothelial function and tissue response to injury. Immune complexes, autoantibodies, complement, cytokines, endothelial injury and a thrombophilic state associated with antiphospholipid antibodies are important for mediating tissue dysfunction. If not treated promptly, a significant proportion of patients—especially those with more aggressive disease—accumulate irreversible damage. During the past decade, novel combinations of immunosuppressive drugs and biologicals have been added to the therapeutic armamentarium. At the same time, the emphasis in the management of lupus has shifted from individual drugs to a strategy that aims at early, sustained remission tailored to disease manifestations and severity with the lowest possible toxicity. Infections and accelerated atherosclerosis (attributed to both traditional and non-traditional risk factors) and thrombosis-related clinical events (including arterial, venous and pregnancy loss) represent a major challenge in the management of the disease. To avoid fragmentation and optimise medical care, evidence and expert-based recommendations have been developed. For the future the authors predict a new taxonomy on the basis of mechanisms rather than clinical empiricism, leading to targeted therapy.
Role of magnetic resonance imaging in predicting relapse in residual masses after treatment of lymphoma.
Authors: M Hill, D Cunningham, D MacVicar, A Roldan, J Husband, R McCready, J Mansi, S Milan, T Hickish
Journal: Journal of Clinical Oncology (1993)

This prospective study of patients treated at the Royal Marsden Hospital Lymphoma Unit was designed to evaluate the role of magnetic resonance imaging (MRI) in the assessment of residual masses evident on computed tomographic (CT) scanning following treatment of lymphoma.All patients had MRI, gallium-67 single-photon emission CT (67Ga SPECT), and erythrocyte sedimentation rate (ESR) performed within 3 months of completing therapy. Patients were monitored for 1 year posttreatment and observed for signs of relapse. Investigation results were correlated with disease status, and the sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) calculated. Time-to-relapse curves were derived and the log-rank test used to determine whether patients with a positive result were more likely to have a relapse within the mass than those with a negative result.Thirty-four patients were studied, 14 of whom relapsed, 11 within the area of residual mass. Overall, MRI had a high specificity (90%), PPV (71%), and NPV (75%), but poor sensitivity (45%). The results for 67Ga SPECT were similar, apart from lower sensitivity (33%). ESR had inferior performance in predicting relapse compared with the other tests. MRI was the only investigation to show statistical significance (P = .14) in predicting relapse, and this was particularly evident in Hodgkin's lymphoma (P = .003). Combining results of 67Ga SPECT and MRI did not improve predictive power.These data demonstrate that MRI is a valuable tool in the setting of a residual mass after treatment, giving clinically useful prognostic information. 67Ga SPECT also has a role, but is less effective in predicting relapse than MRI.
DNA Vaccination with CCL2 DNA Modified by the Addition of an Adjuvant Epitope Protects against “Nonimmune” Toxic Renal Injury
Authors: Guoping Zheng, Yiping Wang, Shi-Hua Xiang, Yuet-Ching Tay, Huiling Wu, Debbie Watson, Jason Coombes, Gopala K. Rangan, Stephen I. Alexander, David C.H. Harris
Journal: Journal of the American Society of Nephrology (2006)

CC-chemokine-encoding DNA vaccine has been reported to be capable of inducing immunologic memory to corresponding pathogenic self CC-chemokines in animal models of autoimmune disease. This study investigated whether introduction of a foreign T helper epitope into monocyte chemoattractant protein 1 (CCL2) DNA vaccine could boost its immunogenicity by inducing strong neutralizing autoantibody against the pathogenic chemokine CCL2 sufficiently to be protective in a classically nonimmune model of disease, Adriamycin nephropathy (AN). Modification of the CCL2 DNA vaccine by replacing a surface loop region of CCL2 sequence with tetanus toxoid T helper epitope P30 elicited a strong self-specific CCL2 autoantibody production, as well as an IFN-gamma-producing T cell cellular response. The increased immunogenicity of modified CCL2 DNA vaccination but not unmodified CCL2 DNA vaccination was protective against functional and structural renal injury in rat AN. The protective effect of the modified CCL2 DNA vaccine was associated with blockade of glomerular and interstitial macrophage recruitment by neutralizing autoantibody against CCL2, which plays a critical role in eliciting renal injury in AN. Therefore, modification with a foreign T helper epitope breaks self-tolerance by inducing a cellular and humoral response against self-protein and provides a strategy to increase the potency of DNA vaccination sufficiently to afford protection in toxin-induced chronic renal disease.
Essential Role for the P55 Tumor Necrosis Factor Receptor in Regulating Hematopoiesis at a Stem Cell Level
Authors: Vivienne I. Rebel, Sheila Hartnett, Geoffrey R. Hill, Suzan B. Lazo-Kallanian, James L.M. Ferrara, Colin A. Sieff
Journal: The Journal of Experimental Medicine (1999)

Hematopoietic stem cell (HSC) self-renewal is a complicated process, and its regulatory mechanisms are poorly understood. Previous studies have identified tumor necrosis factor (TNF)-α as a pleiotropic cytokine, which, among other actions, prevents various hematopoietic progenitor cells from proliferating and differentiating in vitro. However, its role in regulating long-term repopulating HSCs in vivo has not been investigated. In this study, mice deficient for the p55 or the p75 subunit of the TNF receptor were analyzed in a variety of hematopoietic progenitor and stem cell assays. In older p55−/− mice (&amp;gt;6 mo), we identified significant differences in their hematopoietic system compared with age-matched p75−/− or wild-type counterparts. Increased marrow cellularity and increased numbers of myeloid and erythroid colony-forming progenitor cells (CFCs), paralleled by elevated peripheral blood cell counts, were found in p55-deficient mice. In contrast to the increased myeloid compartment, pre-B CFCs were deficient in older p55−/− mice. In addition, a fourfold decrease in the number of HSCs could be demonstrated in a competitive repopulating assay. Secondary transplantations of marrow cells from primary recipients of p55−/− marrow revealed impaired self-renewal ability of p55-deficient HSCs. These data show that, in vivo, signaling through the p55 subunit of the TNF receptor is essential for regulating hematopoiesis at the stem cell level.
Altered inflammasome activity in bacterial acute exacerbations of COPD (AECOPD)
Authors: Efrossini Dima, Matina Kardara, Harilenna Giannakopoulou, Charis Roussos, Nikolaos Koulouris, Nikoletta Rovina
Journal: European Respiratory Journal (2013)

Inflammasome and its products, as part of the innate immune system, can be triggered to assist in defence against invading pathogens. We have previously shown increased levels of IL-18 in induced sputum of stable COPD patients, which were decreased in acute exacerbations of COPD (AECOPD), implying a possible dysregulation of inflammasome in AECOPD. Aim of this study was to assess the inflammasome activity in AECOPD in the case of proven bacterial infections versus AECOPD where only bacterial colonization was proved.  30 patients hospitalized for an infectious AECOPD according to Anthonisen9s criteria were included in the study. We examined the inflammatory properties of induced sputum and assessed bacterial infection using PCR. IL-18, caspase-1, TLR-2, and IL-1b were measured in induced sputum and serum by immunosorbent analysis (ELISA). Immunocytochemistry of IL-18 expression in sputum cells was performed using a mouse monoclonal IL-18 antibody.  IL-18 levels in sputum were found significantly lower in AECOPD caused by a pathogen compared to colonized AECOPD (207 pg/ml (range 47-2301) vs 420 pg/ml (58-1201), p=0.05). Similarly, although non statistically significantly, decreased levels of caspase-1 and TLR2 were found in infectious versus colonized AECOPD (1.6 pg/ml (1.22-19) vs 3.6 pg/ml (1.27-117), p>0.05). IL-1b was statistically significantly increased in induced sputum of infectious AECOPD (539 pg/ml (1.5-973) vs 88 (2.9-989), p  Our data show that in bacterial AECOPD there may be a dysregulated activation of inflammasome mediating IL-18 production.