tbuckley/cabot-search huggingface dataset:
Abstract 1109: Pleiotropic actions of miR-153 support colorectal cancer progression through enhanced invasion and platinum based chemotherapy resistance
Authors: Alex H. Mirnezami, Lei Zhang, Karen Pickard, Veronika Jenei, Marc Bullock, John Strefford, Richard Mitter, Gavin Kelly, John N. Primrose, Gareth Thomas, Graham Packham
Journal: Cancer Research (2012)

Abstract Background &amp; Aims MicroRNAs (miRNA) contribute to carcinogenesis, however comparatively less is understood about their role in cancer progression. The aim of this study was to evaluate miRNA expression during progression of colorectal cancer (CRC) and to identify novel miRNA functions. Methods and results Using miRNA microarray profiling of a human cellular model of CRC progression, we have found highly expressed levels of miR-153 in more advanced tumour stages. MiR-153 upregulation was further verified by qRT-PCR. Subsequently, using laser capture microdissected human CRC tumour epithelium and real-time PCR based TaqMan® profiling, we have demonstrated that miR-153 is upregulated in primary human CRC compared with normal colonic epithelium (p&amp;lt;0.0001), and over-expressed in more advanced CRC stages than early stage disease (p&amp;lt;0.005). We show that miR-153 upregulation leads to increased CRC invasiveness using in vitro transwell invasion assays, and to more closely recreate and model in vivo circumstances, we examined the effect of stably transfected GFP-tagged miR-153 over-expression in CRC using a 3-dimensional organotypic co-culture of SW480 cells and human ex-vivo colonic fibroblast cells. Ectopic expression of miR-153 but not control miRNA resulted in increased invasion of CRC into the underlying stroma of organotypic cultures. Further in vitro functional analysis demonstrated that miR-153 over-expression also promotes chemotherapy resistance to Oxaliplatin and Cisplatin. Upregulation of miR-153 but not scrambled miRNA reduced abundance of activated Caspase 3 indicating that miR-153 is functioning as an anti-apoptotic factor in this context. Mechanistic dissection of the above functional effects show that miR-153 induces CRC invasiveness through increased MMP9 production, while resistance to platinum based chemotherapy is mediated through a direct inhibitory effect on the Forkhead box O3 (FOXO3a) transcription factor. Conclusions This is the first demonstration that over-expressed miR-153 has a significant and dual role in CRC progression, promoting both increased invasiveness and chemotherapy resistance. These findings suggest that strategies to suppress miR-153 may prove useful in advanced CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1109. doi:1538-7445.AM2012-1109
Abstract 4531: Nanoscale Artificial Antigen Presenting Cells for T Cell Immunotherapy.
Authors: Karlo Perica, Joan G. Bieler, Andrés De León Medero, Yen-Ling Chiu, Malarvizhi Durai, Michaela Niemöller, Mario Assenmacher, Anne Richter, Mathias Oelke, Jonathan Schneck
Journal: Cancer Research (2013)

Abstract Artificial antigen presenting cells (aAPC), which deliver stimulatory signals to cytotoxic lymphocytes, are a powerful tool for adoptive immunotherapy and in vivo T cell stimulation. Thus far, bead-based aAPC have been synthesized by coupling T cell activating proteins such as CD3 or MHC-peptide to beads several microns in diameter. By reducing the size of aAPC, we anticipated more efficient delivery of these stimulatory signals to tumor and lymph nodes where antigen-specific T cells reside. We thus manufactured aAPC based on two nanoscale particle platforms: biocompatible iron-dextran paramagnetic particles, 50-100 nm in diameter, and avidin-coated quantum dot nanocrystals, less than 20 nm in diameter. Nanoscale aAPC induced antigen-specific T cell proliferation from both TCR transgenic mouse splenocytes and human, polyclonal peripheral blood T cells. In a subcutaneous mouse melanoma model, both iron-dextran particles and quantum dot nanocrystals mediated tumor rejection when injected in vivo. To our knowledge, this is the first description of a nanoscale, particle-based aAPC that induces T cell proliferation in vitro and leads to effective T cell stimulation and tumor rejection in vivo. Furthermore, nano-aAPC represent a novel platform for studying receptor-ligand interactions at the membrane-nanoparticle interface. Citation Format: Karlo Perica, Joan G. Bieler, Andrés De León Medero, Yen-Ling Chiu, Malarvizhi Durai, Michaela Niemöller, Mario Assenmacher, Anne Richter, Mathias Oelke, Jonathan Schneck. Nanoscale Artificial Antigen Presenting Cells for T Cell Immunotherapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4531. doi:10.1158/1538-7445.AM2013-4531
Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project
Authors: Kenneth R. Carson, Andrew M. Evens, Elizabeth A. Richey, Thomas M. Habermann, Daniele Focosi, John F. Seymour, Jacob Laubach, Susie D. Bawn, Leo I. Gordon, Jane N. Winter, Richard R. Furman, Julie M. Vose, Andrew D. Zelenetz, Ronac Mamtani, Dennis W. Raisch, Gary W. Dorshimer, Steven T. Rosen, Kenji Muro, Numa R. Gottardi-Littell, Robert L. Talley, Oliver Sartor, David Green, Eugene O. Major, Charles L. Bennett
Journal: Blood (2009)
Inference of a molecular defect of apolipoprotein B in hypobetalipoproteinemia by linkage analysis in a large kindred.
Authors: M Leppert, J L Breslow, L Wu, S Hasstedt, P O'Connell, M Lathrop, R R Williams, R White, J M Lalouel
Journal: Journal of Clinical Investigation (1988)

Heterozygous hypobetalipoproteinemia is characterized by reduced plasma concentrations of LDL cholesterol, total triglycerides, and apo B to less than 50% of normal values. The molecular basis of this disorder remains unknown. The phenotype cosegregates with a DNA haplotype of the apo B gene in an Idaho pedigree, with a maximum decimal logarithm of the ratio (LOD) score of 7.56 at a recombination rate of zero. Individuals carrying this haplotype had total cholesterol levels of 96 mg/dl, LDL cholesterol levels of 37 mg/dl, triglycerides levels of 51 mg/dl, and apo B levels of 38 mg/dl. This study strongly suggests that apo B mutations underlie hypobetalipoproteinemia, and demonstrates the power of the candidate gene approach in linkage analysis for unraveling genetic determinants in metabolic disorders of undefined etiology.
Characterization of the hyperpolarization-activated inward current in isolated human atrial myocytes
Authors: Uta C Hoppe, Dirk J Beuckelmann
Journal: Cardiovascular Research (1998)

Objective: The hyperpolarization-activated inward current (If) has been discussed to contribute to arrhythmias in rat hypertrophied and human failing ventricular myocardium. Cat atrial myocytes were found to exhibit variable size of If. In the present study, we evaluate characteristics of If in human atrial myocardium and investigate if human atria might exhibit any electrophysiological heterogeneity in the diastolic voltage range. Methods and results: The whole-cell patch-clamp technique was used to record If in isolated myocytes from 96 human right atrial appendages. If was observed in 95% (ruptured-patch; 141/146) to 100% (perforated-patch; 18/18) of myocytes showing typical current properties, i.e. time- and voltage-dependence, block by [Cs+]o, permeability for K+, Na+ and Li+, and current increase with raising [K+]o. Using the perforated-patch technique Boltzmann distributions yielded an activation threshold of −60 to −70 mV and half maximal activation at −89.3±0.7 mV (n=18). Isoproterenol (10−6 mol/l) shifted If activation by +7 mV (7/7) using the perforated-patch technique, but only inconsistently shifted If activation using the ruptured-patch method (6/21). Based on the relative current size of If and IK1 three cell types could be distinguished (n=26). In myocytes with a prominent If, If density was found to be larger (in [K+]o 25 mmol/l at −80 mV: −0.78±0.23 pApF−1; n=7) than in cells with predominant IK1 (in [K+]o 25 mmol/l at −80 mV: −0.02±0.01 pApF−1; n=4) (P<0.05). Conclusions: If is present in most human atrial myocytes. Many current properties are similar to those described for If in mammalian pacemaker cells. The relative current size of If and IK1 were found to be variable in different myocytes. Whether If may favor spontaneous diastolic depolarization in individual human atrial myocytes exhibiting predominantly If in vivo remains to be defined, as current size is very small under physiological [K+]o.
Magnetic Resonance Images Lipid, Fibrous, Calcified, Hemorrhagic, and Thrombotic Components of Human Atherosclerosis In Vivo
Authors: Jean-Franc¸ois Toussaint, Glenn M. LaMuraglia, James F. Southern, Valentin Fuster, Howard L. Kantor
Journal: Circulation (1996)

Background Although MRI can discriminate the lipid core from the collagenous cap of atherosclerotic lesions in vitro with T2 contrast, it has not yet produced detailed in vivo images of these human plaque components. Methods and Results We imaged seven lesions from six patients who required surgical carotid endarterectomy and calculated T2 in vivo before surgery in various plaque regions. Using the same acquisition parameters, we repeated these measurements in vitro on the resected fragment and compared MR images with histology. T2 values calculated in vivo correlate with in vitro measurements for each plaque component; the in vitro discrimination we demonstrated previously with T2 contrast can therefore be performed similarly in vivo. Conclusions MRI is the first noninvasive imaging technique that allows the discrimination of lipid cores, fibrous caps, calcifications, normal media, and adventitia in human atheromatous plaques in vivo. This technique also characterizes intraplaque hemorrhage and acute thrombosis. This result may support further investigations that include MRI of plaque progression, stabilization, and rupture in human atherosclerosis.
An Unusual Cause of Acute Hematemesis
Authors: N. Thorne Griscom
Journal: JAMA (1963)

Dr. James J. Pollard: This roentgen film (Fig 1) is part of an emergency upper gastrointestinal series done for a 64-year-old white housewife with hematemesis. She had begun to experience occasional epigastric and right upper quadrant pain 10 years prior to admission. A cholecystectomy had been done for cholelithiasis 2 years previously, with remission of her fatty food intolerance and right upper quadrant symptoms. Two weeks prior to admission the patient noted an increase in severity and frequency of the epigastric pain, which was not associated with food or relieved by ingesting an alkali compound. The day before admission she noted melena and vomited one or two cupfuls of dark red blood. She denied excessive intake of alcohol, weight loss, anorexia, and symptoms of liver disease. She had been moderately hypertensive. Physical examination showed a pale, obese female who vomited blood from time to time and passed melenic stools. Her
Utilization and Cost Experience of Low-Income Families in Four Prepaid Group-Practice Plans
Authors: Gerald Sparer, Arne Anderson
Journal: New England Journal of Medicine (1973)

Abstract A number of low-income families through arrangements supported by the Office of Economic Opportunity received medical care through four community-based prepaid group-practice plans. These families required six months to achieve a utilization level not exceeding that of the regular-plan members. As compared to national data, costs were less because of reductions in hospital days for the poor under prepaid group-practice arrangements. The average number of inpatient days per 1000 Office of Economic Opportunity enrollees was 600 days under the group plan; the national average for low-income persons under the age of 65 was about 1000 days. Cost differences between the low-income families and the regular-plan members were minimal when similar benefits were compared. A package of services including comprehensive physician services, prescriptions, mental health and hospital services cost from $137 to $180 per person per year. Support of broader health services may add from $47 to $65 per person per year to the cost. (N Engl J Med 289: 67–72, 1973)
SARS in China spreads from Beijing to poorer inland provinces
Authors: J. Parry
Journal: BMJ (2003)

Hopes of containing the global outbreak of severe acute respiratory syndrome (SARS) have been dealt a blow by the further rise in the number of cases and the wider spread of the virus in China. By 12 May, China accounted for 5013 of the world's total of 7447 cases. Of the worldwide death toll of 552, almost half (252) of the deaths have occurred there.

Although the outbreak in Beijing is in itself worrying, the real cause for concern is the poorer inland provinces where the disease is now being detected, said Peter Cordingley, World Health Organization's spokesman in Manila.

“The WHO's position is if we don't fix China we can't fix the world. Some of the …
Toxicology of Urea Formaldehyde and Polyurethane Foam Insulation
Authors: John C. Harris
Journal: JAMA (1981)

Two types of foam insulation are in wide use. Urea formaldehyde foam is a relatively inexpensive, easily installed, and efficient insulation. Toxicity from this insulation is related to release of free formaldehyde into the home. Mild to incapacitating symptoms have been reported in occupants of urea formaldehyde-insulated homes. Airborne formaldehyde levels frequently have exceeded standards set for occupational exposure. The long-term consequences of such exposure are unknown. Because of publicity over the toxicity of urea formaldehyde foam, many physicians and patients have confused urea formaldehyde and polyurethane foam. Unlike urea formaldehyde, polyurethane foam is fully cured before construction. Toxicity occurs only during manufacture and curing. To date, there have been no reports to our knowledge of toxicity in occupants of polyurethane-insulated homes. However, toxicity caused by pyrolysis products may occur during combustion in homes insulated with either type of insulation. This report details 48 patients in whom complete medical data were obtained out of the first 100 patients contacting the Rocky Mountain Poison Center.
Scabies Resembling Darier's Disease
Authors: Robert I. Rudolph
Journal: JAMA (1982)

<h3>To the Editor.—</h3> Several years ago we reported a case of scabies in an immunosuppressed host that closely simulated Darier's disease.<sup>1</sup>The patient had recently undergone a renal transplant and had been on a maintenance regimen of azathioprine and prednisone. A florid, scaling, papular eruption developed during several weeks that was clinically identical to Darier's disease. Biopsy specimens and skin scrapings showed a scabetic infestation. We believed that the highly atypical presentation, which had several features that were found in Norwegian scabies, was probably due to a decreased inflammatory response as a result of the immunosuppression and which allowed a spectacular proliferation of the mites on the skin surface. The clinical features found in our patient simulated almost exactly those of Darier's disease, and indeed that was the working diagnosis until the biopsy showed the histopathological findings of scabies. I think that the recently reported case (1981; 246:2608) and
Efficacy of retreatment with immunomodulatory drugs (IMiDs) in patients receiving IMiDs for initial therapy of newly diagnosed multiple myeloma
Authors: Sumit Madan, Martha Q. Lacy, Angela Dispenzieri, Morie A. Gertz, Francis Buadi, Suzanne R. Hayman, Kristen Detweiler-Short, David Dingli, Steven Zeldenrust, John Lust, Philip R. Greipp, S. Vincent Rajkumar, Shaji Kumar
Journal: Blood (2011)
Non-hematopoietic allograft cells directly activate CD8+ T cells and trigger acute rejection: An alternative mechanism of allorecognition
Authors: Daniel Kreisel, Alexander S. Krupnick, Andrew E. Gelman, Friederike H. Engels, Sicco H. Popma, Alyssa M. Krasinskas, Keki R. Balsara, Wilson Y. Szeto, Laurence A. Turka, Bruce R. Rosengard
Journal: Nature Medicine (2002)
Fenfluramine Increases Insulin Action in Patients With NIDDM
Authors: Richard G Pestell, Patricia A Crock, Glenn M Ward, Frank P Alford, James D Best
Journal: Diabetes Care (1989)

These studies examined the effect of fenfluramine on insulin action and insulin secretion in healthy subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). In the first study, a double-blind crossover design was used in healthy subjects to compare the effect of short-term fenfluramine therapy (60 mg orally for 3 days) with placebo. Insulin secretion and whole-body insulin sensitivity (determined by frequently sampled intravenous glucose tolerance tests with analysis by the minimal-model method) were unchanged by fenfluramine. In the second study, involving patients with NIDDM inadequately controlled on submaximal to maximal doses of oral hypoglycemic agents, a double-blind crossover strategy was used to compare baseline studies (conducted after a run-in period) with fenfluramine (60 mg orally) or placebo for 4 wk. There was a signficant fall in fasting blood glucose after therapy with fenfluramine compared with the baseline study period (13.0 ± 1.2 vs. 8.4 ± 0.89 mM, mean ± SE, P &amp;lt; .01) with no significant fall in fasting serum insulin (20± 2 vs. 24 ± 3 (μU/ml) or C-peptide (1.3 ± 0.2 vs. 1.3 ± 0.1 nM). During euglycemichyperinsulinemic (1 mU · kg−1 · min−1) clamp studies there was a significant increase in insulin action from 12.7± 2.3 to 17.3 ± 1.8 min−1 103 μU · ml1 (P &amp;lt; .05), although clamp insulin levels were lower after fenfluramine treatment (136 ± 14 vs. 96 ± 9 μU/ml−1, P &amp;lt; .02), reflecting an enhanced metabolic clearance rate for insulin (12.7 ± 1.5 vs. 20.1 ± 2.1 ml · kg−1 · min−1 P &amp;lt; .025). When insulin action was normalized for the prevailing insulin level during the clamp, the increase of insulin action/in concentration was more marked (0.11 ± 0.22 to 0.22 ±0.04 min−1 103μU · ml−1 &amp;lt;.005). The insulin secretory response to arginine was unchanged from 21 ± 4 to 22 ± 6 μU/ml at similar levels of glycemia. Chronic fenfluramine therapy can lower fasting plasma glucose and increase insulin sensitivity without affecting insulin secretion in patients with NIDDM. Acute fenfluramine treatment in healthy individuals has no effect on glucose metabolism. We conclude that in patients with inadequately controlled NIDDM, fenfluramine may serve as a useful adjunct to sulfonylurea therapy.
In Situ Measurement of Colorectal Polyps to Compare Video and Fiberoptic Endoscopes
Authors: B. Hofstad, M. Vatn, S. Larsen, H. S. Huitfeldt, M. Osnes
Journal: Endoscopy (1994)

The present study was performed to test the reliability of in situ measurements of colorectal polyps when comparing videoendoscopes with fiberoptic endoscopes. In 25 small rectosigmoid polyps 3-12 mm) removed endoscopically, in situ diameters were measured before polypectomy using both video- and fiberoptic endoscopes. Polaroid and videoprint pictures were taken for computerised analysis of the area of the polyps on the pictures. The results showed a good correlation between the polyp diameter measured with the videoendoscope and fiberoptic endoscope (r = 0.97), with no significant difference by parametric testing. The diameter and weight of the removed polyp also correlated well with the diameter measured in situ using videoendoscopes (r = 0.92 and 0.77, respectively) or fiberoptic endoscopes (r = 0.90 and 0.81, respectively). Furthermore, the weight of the removed polyp correlated reasonably well to the computerised area measurement, the correlation coefficient being r = 0.90 for fiberoptic endoscopes and r = 0.75 for videoendoscopes. We conclude that in situ polyp diameter measurements using videoendscopes and fiberoptic endoscopes are similarly reliable and sensitive, and both instruments can be used interchangeably in follow-up studies of polyp growth.
In vitro all-trans retinoic acid sensitivity of acute promyelocytic leukemia blasts: a novel indicator of poor patient outcome
Authors: Bruno Cassinat, Sylvie Chevret, Fabien Zassadowski, Nicole Balitrand, Isabelle Guillemot, Marie-Laurence Menot, Laurent Degos, Pierre Fenaux, Christine Chomienne
Journal: Blood (2001)
Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women
Authors: M C Chapuy, M E Arlot, P D Delmans, P J Meunier
Journal: BMJ (1994)

demand among the general practitioners for postmortem reports.Local pathologists and coroners do not routinely supply reports to the general practitioner, but general practitioners clearly want them to.Similar findings have been reported elsewhere.' Irrespective of who requests postmortem examin- ations, the benefits of the findings may be lost if reports are not readily available to the relevant doctors, whether they work in a hospital or in the community.We propose that a copy of every postmortem report should be sent to the family health services authority, which could forward it to the appropriate general practitioner.