tbuckley/cabot-search huggingface dataset:
Role of bile acids and bile acid binding agents in patients with collagenous colitis
Authors: K-A Ung
Journal: Gut (2000)

<h3>BACKGROUND</h3> In a retrospective study bile acid malabsorption was observed in patients with collagenous colitis. <h3>AIMS</h3> To study the occurrence of bile acid malabsorption and the effect of bile acid binders prospectively in patients with chronic diarrhoea and collagenous colitis. <h3>METHODS</h3> Over 36 months all patients referred because of chronic diarrhoea completed a diagnostic programme, including gastroscopy with duodenal biopsy, colonoscopy with biopsies, and the <sup>75</sup>Se-homocholic acid taurine (<sup>75</sup>SeHCAT) test for bile acid malabsorption. Treatment with a bile acid binder (cholestyramine in 24, colestipol in three) was given, irrespective of the results of the <sup>75</sup>SeHCAT test. <h3>RESULTS</h3> Collagenous colitis was found in 28 patients (six men, 22 women), 27 of whom had persistent symptoms and completed the programme. Four patients had had a previous cholecystectomy or a distal gastric resection. The <sup>75</sup>SeHCAT test was abnormal in 12/27 (44%) of the collagenous colitis patients with <sup>75</sup>SeHCAT values 0.5–9.7%, and normal in 15 patients (56%). Bile acid binding treatment was followed by a rapid, marked, or complete improvement in 21/27 (78%) of the collagenous colitis patients. Rapid improvement occurred in 11/12 (92%) of the patients with bile acid malabsorption compared with 10/15 (67%) of the patients with normal <sup>75</sup>SeHCAT tests. <h3>CONCLUSION</h3> Bile acid malabsorption is common in patients with collagenous colitis and is probably an important pathophysiological factor. Because of a high response rate without serious side effects, bile acid binding treatment should be considered for collagenous colitis, particularly patients with bile acid malabsorption.
Cannabinoids Induce Apoptosis of Pancreatic Tumor Cells via Endoplasmic Reticulum Stress–Related Genes
Authors: Arkaitz Carracedo, Meritxell Gironella, Mar Lorente, Stephane Garcia, Manuel Guzmán, Guillermo Velasco, Juan L. Iovanna
Journal: Cancer Research (2006)

Abstract Pancreatic adenocarcinomas are among the most malignant forms of cancer and, therefore, it is of especial interest to set new strategies aimed at improving the prognostic of this deadly disease. The present study was undertaken to investigate the action of cannabinoids, a new family of potential antitumoral agents, in pancreatic cancer. We show that cannabinoid receptors are expressed in human pancreatic tumor cell lines and tumor biopsies at much higher levels than in normal pancreatic tissue. Studies conducted with MiaPaCa2 and Panc1 cell lines showed that cannabinoid administration (a) induced apoptosis, (b) increased ceramide levels, and (c) up-regulated mRNA levels of the stress protein p8. These effects were prevented by blockade of the CB2 cannabinoid receptor or by pharmacologic inhibition of ceramide synthesis de novo. Knockdown experiments using selective small interfering RNAs showed the involvement of p8 via its downstream endoplasmic reticulum stress–related targets activating transcription factor 4 (ATF-4) and TRB3 in Δ9-tetrahydrocannabinol–induced apoptosis. Cannabinoids also reduced the growth of tumor cells in two animal models of pancreatic cancer. In addition, cannabinoid treatment inhibited the spreading of pancreatic tumor cells. Moreover, cannabinoid administration selectively increased apoptosis and TRB3 expression in pancreatic tumor cells but not in normal tissue. In conclusion, results presented here show that cannabinoids lead to apoptosis of pancreatic tumor cells via a CB2 receptor and de novo synthesized ceramide-dependent up-regulation of p8 and the endoplasmic reticulum stress–related genes ATF-4 and TRB3. These findings may contribute to set the basis for a new therapeutic approach for the treatment of pancreatic cancer. (Cancer Res 2006; 66(13): 6748-55)
Fistula First Is Not Always the Best Strategy for the Elderly
Authors: Ranil N. DeSilva, Bhanu K. Patibandla, Yael Vin, Akshita Narra, Varun Chawla, Robert S. Brown, Alexander S. Goldfarb-Rumyantzev
Journal: Journal of the American Society of Nephrology (2013)

Whether placing a fistula first is the superior predialysis approach among octogenarians is unknown. We analyzed data from a cohort of 115,425 incident hemodialysis patients ≥67 years old derived from the US Renal Data System with linked Medicare claims, which allowed us to identify the first predialysis vascular access placed rather than the first access used. We used proportional hazard models to evaluate all-cause mortality outcomes based on first vascular access placed, considering the fistula group as the reference. In the study population, 21,436 patients had fistulas as the first predialysis access placed, 3472 had grafts, and 90,517 had catheters. Those patients with a catheter as the first predialysis access placed had significantly inferior survival compared with those patients with a fistula (HR=1.77; 95% CI=1.73 to 1.81; P<0.001). However, we did not detect a significant mortality difference between those patients with a graft as the first access placed and those patients with a fistula (HR=1.05; 95% CI=1.00 to 1.11; P=0.06). Analyzing mortality stratified by age groups, grafts as the first predialysis access placed had inferior mortality outcomes compared with fistulas for the 67 to ≤79-years age group (HR=1.10; 95% CI=1.02 to 1.17; P=0.007), but differences between these groups were not statistically significant for the 80 to ≤89- and the >90-years age groups. In conclusion, fistula first does not seem to be clearly superior to graft placement first in the elderly, because each strategy associates with similar mortality outcomes in octogenarians and nonagenarians.
Evolutionarily conserved genetic interactions with budding and fission yeast MutS identify orthologous relationships in mismatch repair-deficient cancer cells
Authors: Elena Tosti, Joseph A Katakowski, Sonja Schaetzlein, Hyun-Soo Kim, Colm J Ryan, Michael Shales, Assen Roguev, Nevan J Krogan, Deborah Palliser, Michael-Christopher Keogh, Winfried Edelmann
Journal: Genome Medicine (2014)

The evolutionarily conserved DNA mismatch repair (MMR) system corrects base-substitution and insertion-deletion mutations generated during erroneous replication. The mutation or inactivation of many MMR factors strongly predisposes to cancer, where the resulting tumors often display resistance to standard chemotherapeutics. A new direction to develop targeted therapies is the harnessing of synthetic genetic interactions, where the simultaneous loss of two otherwise non-essential factors leads to reduced cell fitness or death. High-throughput screening in human cells to directly identify such interactors for disease-relevant genes is now widespread, but often requires extensive case-by-case optimization. Here we asked if conserved genetic interactors (CGIs) with MMR genes from two evolutionary distant yeast species (Saccharomyces cerevisiae and Schizosaccharomyzes pombe) can predict orthologous genetic relationships in higher eukaryotes. High-throughput screening was used to identify genetic interaction profiles for the MutSα and MutSβ heterodimer subunits (msh2Δ, msh3Δ, msh6Δ) of fission yeast. Selected negative interactors with MutSβ (msh2Δ/msh3Δ) were directly analyzed in budding yeast, and the CGI with SUMO-protease Ulp2 further examined after RNA interference/drug treatment in MSH2-deficient and -proficient human cells. This study identified distinct genetic profiles for MutSα and MutSβ, and supports a role for the latter in recombinatorial DNA repair. Approximately 28% of orthologous genetic interactions with msh2Δ/msh3Δ are conserved in both yeasts, a degree consistent with global trends across these species. Further, the CGI between budding/fission yeast msh2 and SUMO-protease Ulp2 is maintained in human cells (MSH2/SENP6), and enhanced by Olaparib, a PARP inhibitor that induces the accumulation of single-strand DNA breaks. This identifies SENP6 as a promising new target for the treatment of MMR-deficient cancers. Our findings demonstrate the utility of employing evolutionary distance in tractable lower eukaryotes to predict orthologous genetic relationships in higher eukaryotes. Moreover, we provide novel insights into the genome maintenance functions of a critical DNA repair complex and propose a promising targeted treatment for MMR deficient tumors.
Hyperplastic polyposis: semantics, biology, and endoscopy
Authors: P. M. Lynch
Journal: Gut (2010)

Variant forms of hyperplastic polyps of the colorectum, the so-called sessile serrated polyp (SSP) or sessile serrated adenoma (SSA), have recently been described. These are characterised by crypts whose serrations extend all the way to the crypt base, with a widened base that may extend laterally in a ‘boot shape’. Cytological abnormalities of the sort usually required of traditional adenomas—nuclear enlargement and loss of basal orientation—are not essential to the newer SSA terminology.1–4 A tendency for pathologists to engage in descriptive and terminological splitting have the workaday endoscopist and pathologist struggling to keep up and to decide what is important. One might not care except for the presence of emerging details of associations between sessile serrated lesions and colorectal cancer (CRC).5 6 The complex categorisation of morphological subtypes and the specifics of cancer risk have been abetted by molecular pathology correlations.7 8

Complicating matters in the world of serrated neoplasia of the colorectum has been the relationship between multiple hyperplastic polyps (HPs), or ‘hyperplastic polyposis syndrome (HPS)’ and the serrated morphology/molecular signature/cancer risk story.9 Indeed, the very term hyperplastic polyposis is defined in terms of very arbitrary criteria that have never been validated and almost certainly involves a heterogeneous spectrum of conditions. However confusing the HPS story may be, most would agree that at least when the HPs of HPS are large, right sided and/or part of the SSA spectrum, they are important to endoscopists, pathologists and colorectal surgeons.

In this issue of Gut ( see page 1094 ), members of a seven-institution Netherlands consortium conducted a retrospective review of their 1982–2008 experience with respect to demographic, endoscopic and pathological features in patients with hyperplastic polyposis.10 This …
Expansion of somatically reverted memory CD8+ T cells in patients with X-linked lymphoproliferative disease caused by selective pressure from Epstein-Barr virus
Authors: Umaimainthan Palendira, Carol Low, Andrew I. Bell, Cindy S. Ma, Rachel J.M. Abbott, Tri Giang Phan, D. Sean Riminton, Sharon Choo, Joanne M. Smart, Vassilios Lougaris, Silvia Giliani, Rebecca H. Buckley, Bodo Grimbacher, Frank Alvaro, Amy D. Klion, Kim E. Nichols, Stephen Adelstein, Alan B. Rickinson, Stuart G. Tangye
Journal: The Journal of Experimental Medicine (2012)

Patients with the primary immunodeficiency X-linked lymphoproliferative disease (XLP), which is caused by mutations in SH2D1A, are highly susceptible to Epstein-Barr virus (EBV) infection. Nonetheless, some XLP patients demonstrate less severe clinical manifestations after primary infection. SH2D1A encodes the adaptor molecule SLAM-associated protein (SAP), which is expressed in T and natural killer cells and is required for cytotoxicity against B cells, the reservoir for EBV. It is not known why the clinical presentation of XLP is so variable. In this study, we report for the first time the occurrence of somatic reversion in XLP. Reverted SAP-expressing cells resided exclusively within the CD8+ T cell subset, displayed a CD45RA−CCR7− effector memory phenotype, and were maintained at a stable level over time. Importantly, revertant CD8+ SAP+ T cells, but not SAP− cells, proliferated in response to EBV and killed EBV-infected B cells. As somatic reversion correlated with EBV infection, we propose that the virus exerts a selective pressure on the reverted cells, resulting in their expansion in vivo and host protection against ongoing infection.
Pretransplantation interferon treatment and recurrence of hepatitis B virus infection after liver transplantation for hepatitis B-related end-stage liver disease
Authors: Patrick Marcellin, Didier Samuel, Jorge Areias, Marie-Anne Loriot, Jean-Louis Arulnaden, Michèle Gigou, Marie-FrançOise David, Alain Bismuth, Michel Reynes, Christian Bréchot, Jean-Pierre Benhamou, Henri Bismuth
Journal: Hepatology (1994)

Orthotopic liver transplantation in patients with hepatitis B-related cirrhosis is commonly complicated by reinfection with the hepatitis B virus, with rapidly progressive liver disease and poor survival rate. We assessed the efficacy of prior therapy with recombinant interferon-alpha on the prevention of posttransplantation hepatitis B virus reinfection. Twenty-two patients with hepatitis B-related cirrhosis waiting for liver transplantation received 3 MU (decreased to 1.5 MU in cases of intolerance) of recombinant interferon-alpha until transplantation. The rates of posttransplantation hepatitis B virus reinfection and survival in this group were compared with those in a group of 26 patients previously given transplants for the same disease but not given interferon therapy. The same protocol of HBs antibody passive immunoprophylaxis was applied after transplantation in both groups. Recombinant interferon-alpha was administered for 14 +/- 7 wk. The treatment had an antiviral effect, with disappearance of serum hepatitis B virus DNA in seven of the eight patients initially positive for hepatitis B virus DNA and disappearance of HBeAg in two of the three patients initially positive for HBeAg. Serum hepatitis B virus DNA remained detectable with polymerase chain reaction at transplantation in 56% of the interferon-treated patients. After transplantation, hepatitis B virus reinfection was more frequent in polymerase chain reaction-positive than in polymerase chain reaction-negative patients (78% vs. 17%, p < 0.05). One patient's condition deteriorated during interferon treatment; this patient was not given a transplant. Two patients (in whom hepatitis B virus DNA disappeared from serum) improved so markedly during treatment that they were not given transplants.(ABSTRACT TRUNCATED AT 250 WORDS)
Comparison of Prospective and Retrospective Indicators of the Quality of End-of-Life Cancer Care
Authors: Soko Setoguchi, Craig C. Earle, Robert Glynn, Margaret Stedman, Jennifer M. Polinski, Colleen P. Corcoran, Jennifer S. Haas
Journal: Journal of Clinical Oncology (2008)

To compare prospectively and retrospectively defined benchmarks for the quality of end-of-life care, including a novel indicator for the use of opiate analgesia.Linked claims and cancer registry data from 1994 to 2003 for New Jersey and Pennsylvania were used to examine prospective and retrospective benchmarks for seniors with breast, colorectal, lung, or prostate cancer who participated in state pharmaceutical benefit programs.Use of opiates, particularly long-acting opiates, was low in both the prospective and retrospective cohorts (9.1% and 10.1%, respectively), which supported the underuse of palliative care at the end-of-life. Although hospice was used more commonly in the retrospective versus prospective cohort, admission to hospice within 3 days of death was similar in both cohorts (28.8% v 26.4%), as was the rate of death in an acute care hospital. Retrospective and prospective measures identified similar physician and hospital patterns of end-of-life care. In multivariate models, a visit with an oncologist was positively associated with the use of chemotherapy, opiates, and hospice. Patients who were cared for by oncologists in small group practices were more likely to receive chemotherapy (retrospective only) and less likely to receive hospice (both) than those in large groups. Compared with patients who were cared for in teaching hospitals, those in other hospitals were more likely to receive chemotherapy (both) and to have toxicity (prospective) but were less likely to receive opiates (both) and hospice (retrospective).Retrospective and prospective measures, including a new measure of the use of opiate analgesia, identify some similar physician and hospital patterns of end-of-life care.
Combining lesional short-contact dithranol therapy of psoriasis with a potent topical corticosteroid
Authors: O.Q.J. Swinkels, M. Prins, M. Kucharekova, T. De Boo, M.J.P. Gerritsen, P.G.M. Van Der Valk, P.C.M. Van De Kerkhof
Journal: British Journal of Dermatology (2002)

Since its introduction, the effectiveness of dithranol in treating psoriasis has been unequalled by other topical treatments. Out-patient short-contact dithranol treatment is effective with regard to clinical response rate and relapse rate after 1 year. A drawback, however, is the relatively long treatment duration.To study a dithranol regimen combined with a potent topical corticosteroid with regard to clinical response rate, treatment duration and remission period after clearance.Twelve patients with stable psoriasis vulgaris participated in this study. We treated three comparable psoriasis lesions on the extremities for 39 consecutive days. The first lesion was treated daily with short-contact dithranol cream followed by clobetasol-17-propionate ointment 5 days per week. The second lesion was treated daily with short-contact dithranol cream followed by the vehicle of clobetasol-17-propionate ointment. The third lesion was treated with clobetasol-17-propionate ointment 5 days per week. The patients attended on days 1, 4, 9, 12, 15, 18, 22, 25, 32 and 39 during treatment. We assessed lesional severity scores at each visit and registered the baseline area at the first visit. During the follow up at weeks 2, 4, 6, 10, 14, 19 and 23 we assessed lesional sum scores. We also estimated the area involved in recurrence of the lesion as a percentage of the baseline area. The overall differences between the three treatment curves for the treatment period and follow-up period separately were tested with a likelihood ratio test.Differences between the curves of the sum scores during treatment (P < 0.001) were mainly due to the different time-course of dithranol monotherapy, which showed a slower decrease in sum score. Differences between the linear trends of the sum score (P < 0.001) and the area score P < 0.001) during follow up were due to a different time-course of the combination therapy, which started lower and increased more slowly, suggesting a slower relapse rate with combination therapy. When comparing the follow-up data, it must be kept in mind that the three treatments showed an overall significantly different sum and area score at the start of follow up.Intermittent addition of clobetasol-17-propionate ointment enhanced the antipsoriatic efficacy of short-contact, high-dose dithranol therapy in terms of clearing capacity and treatment duration, without shortening remission duration.
Detection and Quantitation of Circulating Human Irisin by Tandem Mass Spectrometry
Authors: Mark P. Jedrychowski, Christiane D. Wrann, Joao A. Paulo, Kaitlyn K. Gerber, John Szpyt, Matthew M. Robinson, K. Sreekumaran Nair, Steven P. Gygi, Bruce M. Spiegelman
Journal: Cell Metabolism (2015)
Interventions used in disease management programmes for patients with chronic illness---which ones work? Meta-analysis of published reports
Authors: S. R Weingarten
Journal: BMJ (2002)

To systematically evaluate the published evidence regarding the characteristics and effectiveness of disease management programmes.Meta-analysis.Computerised databases for English language articles during 1987-2001.102 articles evaluating 118 disease management programmes.Pooled effect sizes calculated with a random effects model.Patient education was the most commonly used intervention (92/118 programmes), followed by education of healthcare providers (47/118) and provider feedback (32/118). Most programmes (70/118) used more than one intervention. Provider education, feedback, and reminders were associated with significant improvements in provider adherence to guidelines (effect sizes (95% confidence intervals) 0.44 (0.19 to 0.68), 0.61 (0.28 to 0.93), and 0.52 (0.35 to 0.69) respectively) and with significant improvements in patient disease control (effect sizes 0.35 (0.19 to 0.51), 0.17 (0.10 to 0.25), and 0.22 (0.1 to 0.37) respectively). Patient education, reminders, and financial incentives were all associated with improvements in patient disease control (effect sizes 0.24 (0.07 to 0.40), 0.27 (0.17 to 0.36), and 0.40 (0.26 to 0.54) respectively).All studied interventions were associated with improvements in provider adherence to practice guidelines and disease control. The type and number of interventions varied greatly, and future studies should directly compare different types of intervention to find the most effective.
Eradication of Established Tumors by Vaccination With Recombinant<i>Bordetella pertussis</i>Adenylate Cyclase Carrying the Human Papillomavirus 16 E7 Oncoprotein
Authors: Xavier Préville, Daniel Ladant, Benedikt Timmerman, Claude Leclerc
Journal: Cancer Research (2005)

Abstract High-risk human papillomaviruses (HPV) such as HPV16 are associated with the development of cervical cancer. The HPV16-E6 and HPV16-E7 oncoproteins are expressed throughout the replicative cycle of the virus and are necessary for the onset and maintenance of malignant transformation. Both these tumor-specific antigens are considered as potential targets for specific CTL-mediated immunotherapy. The adenylate cyclase (CyaA) of Bordetella pertussis is able to target dendritic cells through specific interaction with the αMβ2 integrin. It has been previously shown that this bacterial protein could be used to deliver CD4+ and CD8+ T cell epitopes to the MHC class II and class I presentation pathways to trigger specific Th and CTL responses in vivo, providing protection against subsequent viral or tumoral challenge. Here, we constructed recombinant CyaA containing either the full sequence or various subfragments from the HPV16-E7 protein. We show that, when injected to C57BL/6 mice in absence of any adjuvant, these HPV16-recombinant CyaAs are able to induce specific Th1 and CTL responses. Furthermore, when injected into mice grafted with HPV16-E7-expressing tumor cells (TC-1), one of these recombinant proteins was able to trigger complete tumor regression in 100% of the animals tested. This therapeutic efficacy compared favorably to that of strongly adjuvanted peptide and was marginally affected by prior immunity to CyaA protein. This study represents the first in vivo demonstration of the antitumoral therapeutic activity of recombinant CyaA proteins carrying human tumor–associated antigens and paves the way for the testing of this vector in clinical trials.