tbuckley/cabot-search huggingface dataset:
OC-068 Structure and function of the gastro-oesophageal junction in patients after laparoscopic fundoplication: concurrent magnetic resonance imaging and high-resolution manometry studies
Authors: M R Fox, E Kaufman, J Curcic, M Wyss, P Schneider, M Fried, P Bösiger, W Schwizer
Journal: Gut (2010)

<h3>Introduction</h3> Laparoscopic fundoplication provides effective reflux control in patients with gastro-oesophageal reflux disease (GERD); however a proportion of patients that undergo surgery experience troublesome symptoms. Improved results may be possible if more was known about the structural factors that effect treatment outcome. This study applied concurrent MRI and HRM technology to compare the structure and function of the GEJ in GERD patients after fundoplication to control groups of GERD patients and healthy participants (HPs). <h3>Methods</h3> Eight GERD patients were studied at least 3 months after laparoscopic fundoplication with subjectively good treatment outcome (7M, age 18–67 years). Results of pH-impedance monitoring off acid suppression before and after fundoplication were available. 12 patients with GERD on medical therapy (7M, age 20–55 years) and 12 HPs (7M, age 26–36 years) with no history of gastro-intestinal disease or surgery. Validated MRI measurements of the oesophago-gastric insertion angle (Radiology in press) and gastric volumes were performed at baseline and after ingestion of high calorie meal (McDonalds Cheeseburger, Chips, Milkshake, 735 kcal). Visual Analogue Scales (100 mm VAS) documented dyspeptic symptoms. <h3>Results</h3> GEJ pressure increased from before to after fundoplication (8.3±1.2 vs 14.2±1.7 mm Hg, p=0.03) whereas acid exposure (10.3±2.2 vs 5.4±2.1, p=0.001) and reflux episodes reduced (39±3 vs 24±2, p=0.019). The insertion angle after the meal was more obtuse after surgery than in the disease and healthy controls (61° vs 48° vs 41°, p&lt;0.008). Moreover normal variation of insertion angle with respiration was lost. Postprandial gastric air content was higher after fundoplication compared to the disease and healthy controls in absolute terms (523 vs 146 vs 178 ml, p&lt;0.001) and as a proportion of total gastric content (78% vs 12% vs 16%, p&lt;0.005). There was a positive correlation between insertion angle and gastric air content (r2=0.95, p=0.050). Postprandial abdominal bloating was higher for the fundoplication group compared to the GERD and healthy groups. (VAS 55±21 vs 13±23 vs 20±10 mm, p=0.049) and there was also an association between gastric air content and the this symptom (r2=0.82, p=0.07). <h3>Conclusion</h3> Novel, quantitative MRI measurements demonstrate alterations to GEJ structure after fundoplication, specifically to the oesophago-gastric insertion angle, that are linked to gastric retention of air and the sensation of bloating, even in patients with a good subjective outcome. Modification of surgical technique to restore more normal GEJ morphology may be equally effective for reflux protection but cause less troublesome bloating.
Efficacy and Safety of Dasatinib in Chronic Myeloid Leukemia Patients in Chronic Phase (CML-CP) with Imatinib Resistance or Intolerance
Authors: Tomoaki Akagi, Kazunori Murai, Kenji Shimosegawa, Kenichi Ishizawa, Tomohiro Sugawara, Hisayuki Yokoyama, Hideyoshi Noji, Kazuei Ogawa, Katsusi Tazima, Koji Ooba, Junichi Sakamoto, Kubo Koumei, Hisashi Sakamaki, Hideo Harigae, Yoji Ishida
Journal: Blood (2011)
A NURSES' STRIKE.
Journal: JAMA (1903)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Renal effects of high-dose celecoxib (CX) and docetaxel (D) During a phase II trial for hormone resistant prostate cancer (HRPC)
Authors: M. Yudd, B. Kasimis, V. Chang, S. Srinivas, S. Hwang, L. Sodagum, I. Rana, A. Anani, I. Boholli, M. Miller
Journal: Journal of Clinical Oncology (2004)

4752 Background: Patients with HRPC were treated with D and high doses of the Cox-2 inhibitor, CX. (Kasimis et al; Proc ASCO 2004 subm) Potential adverse renal effects from prostaglandin inhibition include: 1) acute renal failure (ARF) from vasoconstriction; 2) interstitial nephritis +/- nephrotic syndrome; 3) hyperkalemia (*K); 4) increased sodium (Na) and water reabsorption; 5) hypertension (HTN). Methods: 18 patients with HRPC and median age 73.5 years, received a median of 3 cycles (2–6) of D, 30 mg/m2 IV weekly x 3 of each 4 week cycle, and CX 400 mg bid daily . Chemistry and blood pressure data were collected at baseline and then monthly. The repeated measure analysis with General Linear Model (GLM) and multi-level t test comparison were performed. All cases of ARF and *K were evaluated by nephrologists. Results: Serum K was the only variable that showed a significant difference. Compared to baseline, mean serum K was greater in month 2, (p=0.02), but not in other months. None of the following differed significantly from baseline: glomerular filtration rate (GFR) by Cockroft-Gault formula, serum creatinine, urea, Na, chloride, bicarbonate, calcium; fractional excretion of Na (FENa), transtubular potassium gradient (TTKG), urine osmolarity, urinary protein/creatinine ratio (P/C), or BP. There were 5 cases of ARF in 4 patients; causes were prerenal azotemia in 2, obstruction in 2, and contrast in 1. All cases were reversible, and CX treatment was restarted after a short discontinuation. Two patients developed *K, none > 6.0 mmol/l. Conclusions: The incidence of ARF and *K was low, and the causes were attributed to factors other than CX. Mean serum K was increased only transiently. No statistical differences were found in renal function (calculated GFR, serum creatinine) renal tubular handling of Na, K or water (FENa, TTKG, or urine osmolarity, respectively), urine protein excretion, or blood pressure. These results suggest that high dose CX is well tolerated by the kidneys. Supported by Aventis and Pfizer. No significant financial relationships to disclose.
Impact of deletion 13q14 detected by fluorescence in situ hybridization on outcome after dose-reduced allogeneic stem transplantation in patients with multiple myeloma
Authors: N. Kröger, G. Schilling, P. Liebisch, H. Einsele, A. Nagler, M. Kiehl, J. Perez-Simon, R. Schwerdtfeger, J. San Miguel, A. Zander
Journal: Journal of Clinical Oncology (2004)

6536 Background: We investigated in a retrospective multicenter study the impact of deletion 13q by fluorescence in situ hybridization (FISH) on outcome after dose-reduced allografting in patients with multiple myeloma. Patients and Methods: In 68 out of 140 patients data on deletion 13q detected by FISH were available: 37 patients were FISH negative and 31 FISH positive for deletion 13q14. Patients in both groups were well balanced regarding age, β2-microglobulin, relapse after a prior autograft, donor sex, related and unrelated donor, graft source, CD34+ cell dose, and chemosensitivity at time of transplantation. Results: Patients with deletion 13 had a worse event-free survival and overall survival than patients without deletion 13 (18% vs 42%, p=0.05 and 18% vs 67% p=0.03, respectively). Patients with deletion 13 experienced a higher relapse rate (82% vs 58%, p=0.05), but similar incidence of treatment related mortality at one year (24 vs 18%). In the multivariate analysis, deletion 13q remained a significant risk factor for higher relapse-rate (HR 3.28; 95% CI: 1.31–8.24; p=0.01) and for event-free survival (HR 1.94; 95% CI: 1.03–3.67; p=0.04). For overall survival, two or more prior high-dose chemotherapies were associated with a significant higher probabilty of death (HR: 2.48; 95% CI: 1.19–5.17, p=0.02), while patients with deletion 13q had a nearly two times higher risk for death after after dose-reduced allogeneic stem cell transplantation (HR: 1.94; 95% CI: 0.95–3.98, p=0.07). Conclusion: Deletion 13q14 is an unfavourable factor for outcome after dose-reduced conditioning followed by allogeneic stem cell transplantation in multiple myeloma No significant financial relationships to disclose.
161. Directing Integration of SB Transposons Into Selected Genomic Sites in Liver for Non-Viral Gene Therapy
Authors: Bryan C. Hall, Jason B. Bell, Elena L. Aronovich, Allicia Gunderman, Shayan Farahani, Chelsea Fortin, Perry B. Hackett
Journal: Molecular Therapy (2015)

Insertional mutagenesis is a concern for those practicing gene therapy. Several methods that employ modified recombinases, integrases, and transposases have been proposed and tested to direct integration of transgenic expression cassettes to specific sites in mammalian genomes. Site-specific nucleases employing zinc-fingers (ZFNs), transcription activator-like coupled to endonucleases (TALENs), and RNA-guided nucleases (RGNs, which include the CRISPR/Cas systems) are effective to various extents for site-specific recombination to repair genes as well as direct insertion of new genetic sequences. There are some concerns with cleavage of non-targeted sites that have yet to be resolved using site-specific nucleases. We have been developing an alternative method for directing integration of the Sleeping Beauty (SB) transposon system for non-viral gene therapy. SB transposons nearly randomly integrate into TA sites in genomes (about 2×106 in mammalian genomes) and are agnostic regarding the transcriptional state or purpose of a given region. Our targeting procedure employs the RecA protein from E. coli that is involved with DNA repair and recombination. Single-stranded DNA oligonucleotides (ODNs) complexed with RecA protein can interact with genomic DNA to form triple DNA helices. These can be recognized by some transposases for selective transposition (Fig. 1). We tested whether site-specific integration by SB transposase could be achieved by targeting the MIA14 locus in mouse liver. There are about 2098 copies of the repetitive element in benign locations in the mouse genome. By targeting a repetitive element, the chances of avoiding integration into non-targeted sites theoretically would be reduced. If effective, RecA-mediated targeting for a given transposon (transgene) to any site could be achieved by just specifying a single 40-mer ODN. To test our proposed method for targeting integration, we hydrodynamically infused pT2 transposons carrying a luciferase expression cassette, SB100 transposase, and RecA-40mer filaments into mice. Mice were sacked four days post-infusion, livers were harvested, genomic DNA isolated, and selected regions amplified using bar-coded, transposon-specific primers for analysis of integration sites by Illumina sequencing. Our initial results indicate that this method of targeting integration without using site-specific nucleases has potential.
OP14GENETIC AND FUNCTIONAL DIVERSITY OF PROPAGATING CELLS IN GLIOBLASTOMA
Authors: S.G.M. Piccirillo, S. Colman, N. Potter, F. van Delft, S. Lillis, M. Carnicer, L. Kearney, C. Watts, M. Greaves
Journal: Neuro-Oncology (2015)

INTRODUCTION: Glioblastoma (GBM) is a lethal malignancy whose clinical intransigence has been linked to extensive intraclonal genetic and phenotypic diversity and the common emergence of therapeutic resistance. This interpretation embodies the implicit assumption that cancer stem cells or tumour-propagating cells are themselves genetically and functionally diverse. METHOD: We screened primary GBM by SNP array to identify copy number alterations (a minimum of three) that could be visualized in single cells by multicolor fluorescence in situ hybridization. Interrogation of neurosphere-derived cells (from four patients) and cells derived from secondary transplants of these same cells in NOD-SCID mice allowed us to infer the clonal and phylogenetic architectures. Whole-exome sequencing and single-cell genetic analysis in one case were used to further dissect the complex clonal structure. RESULTS: All together our results show that: (i) GBM can be propagated by multiple stem cell-like clonal populations, (ii) Tumour-propagating clones display genetic and functional diversity, (iii) Clonal phylogenetic analysis reveals the temporal evolution of a fitness advantage, (iv) Competitive propagating ability is associated with TP53 mutation/EGFR amplification. CONCLUSION: This proof-of-principle experiment revealed that subclones in each GBM had variable regenerative or stem cell activity, and highlighted genetic alterations associated with more competitive propagating activity in vivo.
Complex Aberrant Karyotype in Patients with Post-Transplant Relapses of Acute Myeloid and Lymphoid Leukemias Evaluated By Serial Cytogenetic Assays, Including mFISH
Authors: Tatiana L Gindina, Nikolay N Mamaev, Sergey N Bondarenko, Elena V Semyenova, Natalia V Stancheva, Olga A Slesarchuk, Ivan S Moiseev, Boris Afanasyev
Journal: Blood (2014)
Treatment of Philadelphia Chromosome (Ph)-Positive Acute Lymphoblastic Leukemia (ALL) with Concurrent Chemotherapy and Imatinib Mesylate.
Authors: Josep-Maria Ribera, Albert Oriol, Marcos Gonzalez, Maria-Belen Vidriales, Blanca Xicoy, Javier Grau, Jordi Esteve, Salut Brunet, Eloy Del Potro, Maria-Jose Moreno, Mar Tormo, Maria-Victoria Martin-Reina, Guillermo Deben, Ricardo Parody, Juan-Jose Lahuerta, Jesus-Fernando San Miguel
Journal: Blood (2004)
Role of E1B protein-dificient oncolytic virus in breast cancer stem cells
Authors: F. Zhang, Y. Ma, Y. Xu, M. Huang, C. Song, S. Lin, Y. Zhang
Journal: Journal of Clinical Oncology (2009)

e22131 Background: Cancer stem cells have been indicated in the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. In breast cancer, they may reside in the CD44 + CD24 −/low population. Oncolytic adenoviruses enter cells through infection and can kill both proliferating and quiescent cells. We investigated the role of E1B protein- dificient oncolytic adenovirus in breast cancer stem cells. Methods: MCF-7 cells were infected by E1B protein-dificient oncolytic adenovirus as infected group (MOI=100) and cultured routinely as control group simultaneously. The proportion of CD44 + CD24 - cells was assessed by flow cytometry (FCM) in two groups respectively. Meanwhile, mammosphere culture was done in two groups' cells to observe the size and number of mammospheres, calculate the mammosphere- forming efficiency (MFE). The proportion of CD44 + CD24 - cells in two groups' mammospheres was assessed by FCM. Results: The percentages of CD24 - ,CD44 + , CD44 + CD24 - in the infected gruop were 43.9%, 63.26%, 22.19%, respectively. While in the control group, the percentages were 6.74%, 88.30%, 2.30%. In the infected group, the time of mammosphere's formation was earlier, the volumes of mammospheres were bigger and the MFE was higher than the control group (1.26%:0.9%). In two mammospheres' groups, the proportion of CD44 + CD24 - cells in experiment group and control group was 38.08% and 23.35%, respectively. Conclusions: E1B protein-dificient oncolytic adenovirus can kill MCF-7 cells in short time, mainly breast cancer differentiated cells. It maybe promote the growth of the breast cancer stem cells. It maybe accelerate the speed of self-renewed and differentiation of the breast cancer stem cells. No significant financial relationships to disclose.
CC-009 Ascites of unknown origin
Authors: I Tanswell, H Steed
Journal: Gut (2010)

<h3>Introduction</h3> Case presentation: A 68-year-old man presented with a 3-month history of anorexia, weight loss and increasing abdominal girth. He was known to have type 2 diabetes mellitus and no history of alcohol excess was obtained. Physical examination revealed tense ascites in the absence of stigmata of chronic liver disease. Cardiovascular examination was normal. The serum-ascites albumin gradient (SA-AG) was 5 g/l. <h3>Methods</h3> Initial bloods revealed normal full blood count, clotting, renal and liver function excepting a low albumin of 34 g/l. Ascitic fluid amylase was normal, cytological examination revealed lymphocytes, macrophages, mesothelial cells, pools of mucin and a negative gram stain. Ultrasound of the abdomen confirmed portal, hepatic and splenic vein patency, normal liver size with no focal lesions and ascites of varying density. <h3>Results</h3> A computed tomographic (CT) scan revealed a discrete, low attenuation mass in the right iliac fossa with a central area of calcification, consistent with an appendiceal mucinous tumour. Scalloping of the liver surface occurs secondary to mucinous intraperitioneal loculi. Laparoscopy showed mucinous deposits on the peritoneal surface. Pathological examination of the omental biopsies revealed abundant extracellular mucin with epithelial cells being CK20 positive, consistent with an appendiceal origin. This patient had primary appendiceal mucinous tumour with mucinous ascites (pseudomyxoma peritionei). <h3>Conclusion</h3> Case discussion: Pseudomyxoma peritionei is a rare malignant condition that may also present with altered bowel habit and infertility in women. It is more common in women, usually secondary to mucinous ovarian tumours. It is characterised by a large volume of mucinous ascites (“jelly-belly”) and is a histological diagnosis. Ultrasound-guided biopsy of the greater omentum has a high sensitivity (95.6%) and specificity (93.8%) in distinguishing malignant ascites from benign ascites. Treatment is primarily surgical peritonectomy (cytoreductive surgery) with intraoperative hyperthermic intraperitoneal chemotherapy.
744. Optimizing Conditions for Aptamer Folding Using a High-Throughput Aptamer Fluorescence Binding and Internalization (AFBI) Assay
Authors: David D. Dickey, Paloma H. Giangrande, William H. Thiel
Journal: Molecular Therapy (2016)

Aptamers are small structured RNA or DNA oligonucleotides that bind target molecules with high avidity and affinity. Aptamer selection begins with a hugely complex library of aptamer sequences that are enriched for a specific target using the SELEX process, Systematic Evolution of Ligands by EXponentional enrichment. An important consideration in the SELEX process is the protocol used to fold aptamers into their active conformations. The folding conditions include multiple variables, such as temperature, buffer components, incubation time and aptamer concentration. Aptamer folding protocols vary widely across the aptamer field, and most published folding conditions primarily describe only temperature and folding time. To understand how variations in folding conditions impact aptamer function, we developed a novel high-throughput assay to interrogate the optimal folding conditions of several published aptamers. The Aptamer Fluorescence Binding and Internalization (AFBI) assay is a cell-based platform that uses a 96-well plate format to rapidly and efficiently screen multiple fluorescent-labelled aptamers against hundreds of conditions. The AFBI assay can be applied to rapidly determine aptamer binding constants (Kd) on cells, time course of aptamer internalization and cross reactivity of aptamers against different cell types. Using the AFBI assay, we screened several different folding parameters against published aptamers. We found that the buffer components contributed significantly more to an aptamer's function than any other examined factor. The concentration of an aptamer during folding was important for some aptamers but not others, including aptamers that originated from the same selection. Most surprising was that most temperature protocols had little impact on aptamer function after folding, the exception being that high temperature (95°C) often attenuated aptamer function. In summary, our data using the AFBI assay revealed that aptamer folding is more dependent on buffer components than the temperature protocol. Furthermore, aptamers derived from the same selection may have different optimal folding conditions. These data demonstrate that optimal aptamer folding protocols need to be more carefully interrogated on a per aptamer basis and reported in detail to allow for efficacious and reproducible results.
Hepatocyte autotaxin expression promotes liver fibrosis and cancer
Authors: Eleanna Kaffe, Aggeliki Katsifa, Nikos Xylourgidis, Ioanna Ninou, Markella Zannikou, Vaggelis Harokopos, Pelagia Foka, Alexios Dimitriadis, Kostas Evangelou, Anargyros N. Moulas, Urania Georgopoulou, Vassilis G. Gorgoulis, George N. Dalekos, Vassilis Aidinis
Journal: Hepatology (2016)

Autotaxin (ATX) is a secreted lysophospholipase D that catalyzes the production of lysophosphatidic acid (LPA), a pleiotropic growth-factor-like lysophospholipid. Increased ATX expression has been detected in various chronic inflammatory disorders and different types of cancer; however, little is known about its role and mode of action in liver fibrosis and cancer. Here, increased ATX expression was detected in chronic liver disease (CLD) patients of different etiologies, associated with shorter overall survival. In mice, different hepatotoxic stimuli linked with the development of different forms of CLDs were shown to stimulate hepatocyte ATX expression, leading to increased LPA levels, activation of hepatic stellate cells (HSCs), and amplification of profibrotic signals. Hepatocyte-specific, conditional genetic deletion and/or transgenic overexpression of ATX established a liver profibrotic role for ATX/LPA, whereas pharmacological ATX inhibition studies suggested ATX as a possible therapeutic target in CLDs. In addition, hepatocyte ATX ablation and the consequent deregulation of lipid homeostasis was also shown to attenuate hepatocellular carcinoma (HCC) development, thus implicating ATX/LPA in the causative link of cirrhosis and HCC.ATX is a novel player in the pathogenesis of liver fibrosis and cancer and a promising therapeutic target. (Hepatology 2017;65:1369-1383).
Hypomethylating Agents Improve Overall Survival in Higher Risk Chronic Myelomonocytic Leukemia (CMML)
Authors: Eric Padron, Najla H Al Ali, Deniz Peker, Jeffrey E Lancet, P.K. Epling-Burnette, Ling Zhang, Alan F. List, Rami S. Komrokji
Journal: Blood (2012)
A Nationwide Prospective Multicenter Study of Clinical Features and Outcomes of Non-Hodgkin Lymphoma in Thailand: An Analysis of 939 Cases
Authors: Udomsak Bunworasate, Noppadol Siritanaratanakul, Archrop Khuhapinant, Arnuparp Lekhakula, Pairaya Rujirojindakul, Chittima Sirijerachai, Kanchana Chansung, Tawatchai Suwanban, Suporn Chuncharunee, Pimjai Niparuck, Weerasak Nawarawong, Lalita Norasetthada, Nonglak Kanitsap, Wichean Mongkonsritragoon, Tontanai Numbenjapon, Kannadit Prayongratana, Rachanid Pornvipavee, Tanin Intragumtornchai
Journal: Blood (2011)
Results of Bortezomib (BTZ) Therapy for Myeloma (MM) Patients Relapsing after an Allogeneic Transplant. Preliminary Results Show Efficacy without Induction of GVHD.
Authors: Sergio Giralt, Ana Aleman, Xin Lei, Marilyn Davis, Kerry Mickler, Donna Weber, Michael Wang, Richard Champlin
Journal: Blood (2004)