tbuckley/cabot-search huggingface dataset:
Intestinal alkaline phosphatase in bile: evidence for an enterohepatic circulation.
Authors: T W Warnes, P Hine, G Kay, A Smith
Journal: Gut (1981)

The isoenzyme characteristics of alkaline phosphatase in human bile obtained from patients with gallstones have been determined by means of electrophoresis on polyacrylamide gel, both before and after preincubation with neuraminidase, and also by means of inhibition tests with heat, urea, and L-phenylalanine. Bile alkaline phosphatase is shown to be partly secreted by the liver cell, but partly derived from the small intestine. The presence of small-intestinal alkaline phosphatase in bile implies an enterohepatic circulation of this high molecular weight glycoprotein. The significance of this finding is discussed in relation to the mechanism whereby large protein molecules may pass across the plasma membrane of the liver cell.
Bruton tyrosine kinase inhibition is a novel therapeutic strategy targeting tumor in the bone marrow microenvironment in multiple myeloma
Authors: Yu-Tzu Tai, Betty Y. Chang, Sun-Young Kong, Mariateresa Fulciniti, Guang Yang, Yolanda Calle, Yiguo Hu, Jianhong Lin, Jian-Jun Zhao, Antonia Cagnetta, Michele Cea, Michael A. Sellitto, Mike Y. Zhong, Qiuju Wang, Chirag Acharya, Daniel R. Carrasco, Joseph J. Buggy, Laurence Elias, Steven P. Treon, William Matsui, Paul Richardson, Nikhil C. Munshi, Kenneth C. Anderson
Journal: Blood (2012)
Effects of rolipram on responses to acute and chronic antigen exposure in monkeys.
Authors: C R Turner, C J Andresen, W B Smith, J W Watson
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The following study was performed to test the hypothesis that treatment with rolipram, a specific inhibitor of phosphodiesterase (PDE) IV, should inhibit many pulmonary responses to acute and chronic antigen challenge in atopic monkeys by elevating intracellular cAMP and subsequently inhibiting leukocyte function. Monkeys received subcutaneous injections of either vehicle (2% DMSO) or 10 mg/kg of rolipram 1 h before exposure to Ascaris suum antigen (Ag). Acute responses to Ag, including bronchoconstriction, pulmonary leukocyte infiltration, and cytokine production, were monitored before and 4 h after single Ag aerosol administration. To monitor the effects of rolipram on chronic Ag exposure, a 10-d, multiple-Ag protocol, previously demonstrated to induce airway hyperresponsiveness (AHR) to methacholine (MCh), was performed. Ag exposure increased respiratory system resistance (Rrs) 221.7 +/- 31.88% (n = 5). This increase in Rrs was not significantly altered by rolipram. Rolipram significantly (p < 0.002) increased cAMP levels in bronchoalveolar lavage (BAL) leukocytes 1 h after administration (n = 5). Ag-induced increases in BAL IL-8 and TNF were significantly reduced by rolipram, but IL-1 beta and IL-6 increases were unaffected (n = 9). Ag-induced increases in BAL eosinophils and neutrophils were significantly reduced by rolipram (n = 9). In the multiple-Ag protocol (n = 7), rolipram significantly reduced both the number of BAL eosinophils (p < 0.02) and the development of AHR (p < 0.002). Despite its inability to inhibit acute Ag-induced bronchoconstriction, rolipram was protective against acute and chronic inflammatory responses to Ag and prevented the development of AHR, suggesting that selective PDE-IV inhibition is a relevant target for asthma therapy.
A systems view on revenge and forgiveness systems
Authors: Tyler J. Wereha, Timothy P. Racine
Journal: Behavioral and Brain Sciences (2012)

Abstract Applying a non-developmental evolutionary metatheory to understanding the evolution of psychological capacities leads to the creation of models that mischaracterize developmental processes, misattribute genes as the source of developmental information, and ignore the myriad developmental and contextual factors involved in human decision-making. Using an evolutionary systems perspective, we argue that revenge and forgiveness cannot be understood apart from the development of foundational human psychological capacities and the contexts under which they develop.
Light Chain–Induced Acute Renal Failure Can Be Reversed by Bortezomib-Doxorubicin-Dexamethasone in Multiple Myeloma: Results of a Phase II Study
Authors: Heinz Ludwig, Zdenek Adam, Roman Hajek, Richard Greil, Elena Tóthová, Felix Keil, Eva Maria Autzinger, Josef Thaler, Heinz Gisslinger, Alois Lang, Miklós Egyed, Irene Womastek, Niklas Zojer
Journal: Journal of Clinical Oncology (2010)

To assess the efficacy of bortezomib-doxorubicin-dexamethasone (BDD) therapy in patients with multiple myeloma with light chain-induced acute renal failure.Sixty-eight patients with light chain-induced acute renal failure and glomerular filtration rate (GFR) less than 50 mL/min received bortezomib (1.0 mg/m(2) on days 1, 4, 8, and 11), doxorubicin (9 mg/m(2) on days 1 and 4), and dexamethasone (40 mg on days 1, 4, 8, and 11); if well tolerated after two cycles, bortezomib could be increased to 1.3 mg/m(2) and doxorubicin administered on days 1, 4, 8, and 11.By intent-to-treat analysis a myeloma response was obtained in 72% of 18 previously and 50 not previously treated patients (complete response [CR]/near CR [nCR], 38%; very good partial response [VGPR], 15%; partial response [PR], 13%; minor response [MR], 6%). Renal response was achieved in 62% of patients (renal CR, 31%; renal PR, 7%; renal MR, 24%). Median GFR increased from 20.5 to 48.4 mL/min. GFR improvement correlated with tumor response; the greatest increase to 59.6 mL/min was seen in the group of patients with CR/nCR/VGPR. Median progression-free survival was 12.1 months. One- and 2-year survival rates were 72% and 58%, respectively. Survival did not differ between patients with and without renal response but was inferior in previously treated patients (P < .001). In multivariate analysis, baseline GFR and tumor response correlated with renal response, and pretreatment status, lactate dehydrogenase, and myeloma response correlated with survival. The most common grade 3 or 4 toxicities were infection (19.1%), thrombocytopenia (14.7%), neutropenia (14.7%), fatigue/weakness (10.3%), and polyneuropathy (8.8%).BDD induced a high rate of myeloma and renal responses, and treatment was well tolerated.
Which patients stop working because of RA?
Authors: E M Shanahan
Journal: Annals of the Rheumatic Diseases (2002)

The paper by Young et al is a useful contribution to the question of work disability related to rheumatoid arthritis.1

However, one of the areas in which intervention is theoretically possible to reduce disability—namely, that of work place intervention, was not discussed. In the study by Young et al the types of work performed by the study cohort are grouped into four categories—namely, manual, semi-manual, semi-sedentary, and mainly sedentary. Presumably, the patients were allocated to a group based on job title using the British classification of occupations …
The sociobiology of sociopathy: An alternative hypothesis
Authors: Wim E. Crusio
Journal: Behavioral and Brain Sciences (2004)

Mealey argued that sociopathy is an evolutionary stable strategy subject to frequency-dependent selection – high levels of sociopathy being advantageous to the individual if population-wide frequencies of it are low, and vice versa. I argue that at least one alternative hypothesis exists that explains her data equally well. Alternative hypotheses must be formulated and tested before any theory can be validated.
RANK signals from CD4+3− inducer cells regulate development of Aire-expressing epithelial cells in the thymic medulla
Authors: Simona W. Rossi, Mi-Yeon Kim, Andreas Leibbrandt, Sonia M. Parnell, William E. Jenkinson, Stephanie H. Glanville, Fiona M. McConnell, Hamish S. Scott, Josef M. Penninger, Eric J. Jenkinson, Peter J.L. Lane, Graham Anderson
Journal: The Journal of Experimental Medicine (2007)

Aire-expressing medullary thymic epithelial cells (mTECs) play a key role in preventing autoimmunity by expressing tissue-restricted antigens to help purge the emerging T cell receptor repertoire of self-reactive specificities. Here we demonstrate a novel role for a CD4(+)3(-) inducer cell population, previously linked to development of organized secondary lymphoid structures and maintenance of T cell memory in the functional regulation of Aire-mediated promiscuous gene expression in the thymus. CD4(+)3(-) cells are closely associated with mTECs in adult thymus, and in fetal thymus their appearance is temporally linked with the appearance of Aire(+) mTECs. We show that RANKL signals from this cell promote the maturation of RANK-expressing CD80(-)Aire(-) mTEC progenitors into CD80(+)Aire(+) mTECs, and that transplantation of RANK-deficient thymic stroma into immunodeficient hosts induces autoimmunity. Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-tolerance.
Microalbuminuria modifies the mortality risk associated with electrocardiographic ST-T segment changes
Authors: Gilles F.H Diercks, Hans L Hillege, A.d J van Boven, Jan A Kors, Harry J.G.M Crijns, Diederick E Grobbee, Paul E de Jong, Wiek H van Gilst
Journal: Journal of the American College of Cardiology (2002)
Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli
Authors: Karin S. Peterson, Jing-Feng Huang, Jessica Zhu, Vivette D’Agati, Xuejun Liu, Nancy Miller, Mark G. Erlander, Michael R. Jackson, Robert J. Winchester
Journal: Journal of Clinical Investigation (2004)

The molecular pathogenesis of focal/diffuse proliferative lupus glomerulonephritis was studied by cDNA microarray analysis of gene expression in glomeruli from clinical biopsies. Transcriptional phenotyping of glomeruli isolated by laser-capture microscopy revealed considerable kidney-to-kidney heterogeneity in increased transcript expression, resulting in four main gene clusters that identified the presence of B cells, several myelomonocytic lineages, fibroblast and epithelial cell proliferation, matrix alterations, and expression of type I IFN–inducible genes. Glomerulus-to-glomerulus variation within a kidney was less marked. The myeloid lineage transcripts, characteristic of those found in isolated activated macrophages and myeloid dendritic cells, were widely distributed in all biopsy samples. One major subgroup of the samples expressed fibrosis-related genes that correlated with pathological evidence of glomerulosclerosis; however, decreased expression of TGF-β1 argued against its role in lupus renal fibrosis. Expression of type I IFN–inducible transcripts by a second subset of samples was associated with reduced expression of fibrosis-related genes and milder pathological features. This pattern of gene expression resembled that exhibited by activated NK cells. A large gene cluster with decreased expression found in all samples included ion channels and transcription factors, indicating a loss-of-function response to the glomerular injury.
British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus
Authors: Rebecca C Fitzgerald, Massimiliano di Pietro, Krish Ragunath, Yeng Ang, Jin-Yong Kang, Peter Watson, Nigel Trudgill, Praful Patel, Philip V Kaye, Scott Sanders, Maria O'Donovan, Elizabeth Bird-Lieberman, Pradeep Bhandari, Janusz A Jankowski, Stephen Attwood, Simon L Parsons, Duncan Loft, Jesper Lagergren, Paul Moayyedi, Georgios Lyratzopoulos, John de Caestecker
Journal: Gut (2013)

These guidelines provide a practical and evidence-based resource for the management of patients with Barrett9s oesophagus and related early neoplasia. The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument was followed to provide a methodological strategy for the guideline development. A systematic review of the literature was performed for English language articles published up until December 2012 in order to address controversial issues in Barrett9s oesophagus including definition, screening and diagnosis, surveillance, pathological grading for dysplasia, management of dysplasia, and early cancer including training requirements. The rigour and quality of the studies was evaluated using the SIGN checklist system. Recommendations on each topic were scored by each author using a five-tier system (A+, strong agreement, to D+, strongly disagree). Statements that failed to reach substantial agreement among authors, defined as &gt;80% agreement (A or A+), were revisited and modified until substantial agreement (&gt;80%) was reached. In formulating these guidelines, we took into consideration benefits and risks for the population and national health system, as well as patient perspectives. For the first time, we have suggested stratification of patients according to their estimated cancer risk based on clinical and histopathological criteria. In order to improve communication between clinicians, we recommend the use of minimum datasets for reporting endoscopic and pathological findings. We advocate endoscopic therapy for high-grade dysplasia and early cancer, which should be performed in high-volume centres. We hope that these guidelines will standardise and improve management for patients with Barrett9s oesophagus and related neoplasia.
Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case–control studies
Authors: Celeste Leigh Pearce, Claire Templeman, Mary Anne Rossing, Alice Lee, Aimee M Near, Penelope M Webb, Christina M Nagle, Jennifer A Doherty, Kara L Cushing-Haugen, Kristine G Wicklund, Jenny Chang-Claude, Rebecca Hein, Galina Lurie, Lynne R Wilkens, Michael E Carney, Marc T Goodman, Kirsten Moysich, Susanne K Kjaer, Estrid Hogdall, Allan Jensen, Ellen L Goode, Brooke L Fridley, Melissa C Larson, Joellen M Schildkraut, Rachel T Palmieri, Daniel W Cramer, Kathryn L Terry, Allison F Vitonis, Linda J Titus, Argyrios Ziogas, Wendy Brewster, Hoda Anton-Culver, Alexandra Gentry-Maharaj, Susan J Ramus, A Rebecca Anderson, Doerthe Brueggmann, Peter A Fasching, Simon A Gayther, David G Huntsman, Usha Menon, Roberta B Ness, Malcolm C Pike, Harvey Risch, Anna H Wu, Andrew Berchuck
Journal: The Lancet Oncology (2012)

Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer.
Impact of hepatitis B virus surface protein mutations on the diagnosis of occult hepatitis B virus infection
Authors: Mira El Chaar, Daniel Candotti, Anthony R. Crowther, Jean Pierre Allain
Journal: Hepatology (2010)

Genotype D occult hepatitis B virus (HBV) infections (OBIs) have a high frequency of amino acid substitutions in the major hydrophilic region of the small surface protein (S protein). This possibly reflects an escape mutation mechanism to evade detection by the host immune system. Mutations may also impact the detection of hepatitis B surface antigen (HBsAg) by commercial assays. To test these hypotheses, 20 recombinant HBV genotype D surface proteins from OBI carriers with or without antibody to hepatitis B surface antigen (anti-HBs) were expressed in yeast. Recombinant surface protein (rS protein) variants were nonreactive with autologous anti-HBs but reacted weakly with vaccine-induced anti-HBs supporting an immune escape mechanism. rS protein variants tested with a wide range of HBs antibodies, and HBsAg commercial assays showed significantly lower antigenic reactivity in anti-HBs carriers than in donors with antibody to hepatitis B core antigen (anti-HBc) only. Eight out of 10 recombinant variants from anti-HBs carriers reacted weakly or were nonreactive with antibodies to HBs as well as with qualitative and quantitative commercial HBsAg assays, whereas eight out of 10 anti-HBc–only plasmas were fully reactive. rS proteins with substitutions of wild-type cysteine at positions 121, 124, and 137 were nonreactive or showed poor reactivity. However, mutation of cysteine 147 did not alter reactivity compared with controls. Restoration of cysteines 124 and 137 by site-directed mutagenesis improved antigenic reactivity. Conclusion: Escape mutation is a mechanism associated with OBI, which also leads to decreased reactivity in HBsAg detection assays. Performance of commercial assays would be improved by the incorporation of OBI mutants in reagent development. (Hepatology 2010)
Presence of sarcopenia (muscle wasting) in patients with nonalcoholic steatohepatitis
Authors: Danny Issa, Naim Alkhouri, Cynthia Tsien, Shetal Shah, Rocio Lopez, Arthur McCullough, Srinivasan Dasarathy
Journal: Hepatology (2013)

We read with great interest the article by Hong et al.1 Hong et al. report an increased risk of nonalcoholic fatty liver disease in patients with lower muscle mass. Here we share the results of a study we conducted to investigate the presence of sarcopenia in patients with nonalcoholic steatohepatitis (NASH) and NASH-related cirrhosis. NASH is an aggressive form of nonalcoholic fatty liver disease. It is widely accepted now that NASH is associated with insulin resistance,2 and can progress to cirrhosis in 21-28% of patients.3 Proinflammatory cytokines and insulin resistance result in muscle catabolism leading to muscle wasting (sarcopenia) in obese patients.4 In addition, sarcopenia is being more frequently described and addressed in cirrhosis patients.5 In our study we divided the subjects into three groups, each one included 25 individuals: a control group, NASH, and NASH-cirrhosis groups. The diagnosis of NASH was proven by liver biopsy. To assess the presence of sarcopenia, we evaluated the muscle mass by measuring the cross-sectional area of the psoas and paraspinal muscles at the level of the midpoint of L4 vertebra on a computed tomography (CT) scan.6 Total psoas and paraspinal muscles densities were also measured. Analysis of covariance was performed to assess differences in muscle area while adjusting for age and gender. Our results showed that patients with NASH and NASH-related cirrhosis were older and had a higher body mass index than the control group. There was a stepwise significant decrease in total psoas area (TPA) from the control group to NASH group to cirrhosis group (29.3 ± 0.88 cm2, 24.8 ± 0.8 cm2, and 19.3 ± 0.93 cm2, respectively, P < 0.001). This difference remained significant after adjusting for age, gender, and height (Fig. 1). Similar findings were noted for the paraspinal muscle area. The density of the muscles as assessed by Hounsfield units (HU) was lower in patients with NASH or cirrhosis, suggesting fatty infiltration (controls 36.9 ± 2.6 HU, NASH 31.2 ± 2.3, cirrhosis 18.5 ± 2.7). In conclusion, our data suggest that there is progressive muscle wasting in patients with NASH that precedes the development of cirrhosis and worsens with progression to cirrhosis. Danny Issa, M.D. Naim Alkhouri, M.D. Cynthia Tsien, M.D. Shetal Shah, M.D. Rocio Lopez, M.S. Arthur McCullough, M.D. Srinivasan Dasarathy, M.D. Cleveland Clinic Pediatric Gastroenterology Cleveland, OH
Effect of perturbation of specific folate receptors during in vitro erythropoiesis.
Authors: A C Antony, E Bruno, R A Briddell, J E Brandt, R S Verma, R Hoffman
Journal: Journal of Clinical Investigation (1987)

Although antisera to specific placental folate receptors inhibits the uptake of 5-methyltetrahydrofolate into cultured malignant human cells, little is known of the functional significance of folate receptors in normal human cells. Human bone marrow cells were therefore assayed for erythropoietic burst-forming units in the presence of an antihuman placental folate receptor serum and preimmune serum to determine the role of such a receptor in erythroid differentiation. When marrow cells were assayed in the presence of anti-receptor antiserum, there was (i) a threefold increase in erythropoietic burst formation and a twofold increase in the number of cells per erythroid burst; (ii) morphological evidence for nuclear/cytoplasmic dissociation of orthochromatic normoblasts composing erythroid bursts (megaloblastic erythropoiesis); (iii) intracellular folate deficiency with a 70% reduction of intracellular folate in antiserum treated cells as compared with control cells; and (iv) complete reversal of antiserum-induced changes on preincubation of antiserum with purified human placental folate receptor. These data support the conclusion that folate receptors on marrow cells provide an important function in the cellular uptake of folates during in vitro erythropoiesis. This process of folate uptake also appears to play a pivotal role in the differentiation and proliferation of erythroid progenitor cells.
Smoking, thrombus, and plaque in the culprit vessel in patients with acute myocardial infarction: angioscopic findings
Authors: Toshiya Kurotobi, Atsushi Hirayama, Yasunori Ueda, Masahiko Shimizu, Tomohito Ohtani, Kazuhisa Kodama
Journal: Journal of the American College of Cardiology (2002)
The treatment of viral warts with topical cidofovir 1%: our experience of seven paediatric patients
Authors: S. Field, A.D. Irvine, B. Kirby
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, Warts caused by human papillomavirus (HPV) can represent a therapeutic challenge. Recently topical, intralesional and intravenous cidofovir has been reported for treatment of viral warts in children1–4 and adults.5 6–7 Cidofovir is a potent nucleoside analogue antiviral agent, which acts as a competitive inhibitor of DNA polymerase.8 Cidofovir is licensed for parenteral treatment of cytomegalovirus retinitis in patients with acquired immune deficiency syndrome. We present a series of seven children treated with topical cidofovir 1% ointment for severe recalcitrant viral warts that were limiting quality of life. Cidofovir 1% in Unguentum M® ointment (Reckitt Benckiser, Hull, U.K.) was compounded from the injectable cidofovir 75 mg mL−1 (Vistide®, Gilead, Foster City, CA, U.S.A.) by St Mary's Pharmaceutical Unit, Cardiff. The ointment was applied in a thin layer to each individual wart at night; the area was occluded with a simple dressing. Of the seven children four were male and ages ranged from 9 to 12 years. Five children had warts on their hands and two on their feet. All children had failed to respond to at least two other forms of therapy (Table 1). The warts had persisted for a mean of 2 years (range 1·5–3).
Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study
Authors: Thomas W Geisbert, Amy CH Lee, Marjorie Robbins, Joan B Geisbert, Anna N Honko, Vandana Sood, Joshua C Johnson, Susan de Jong, Iran Tavakoli, Adam Judge, Lisa E Hensley, Ian MacLachlan
Journal: The Lancet (2010)