tbuckley/cabot-search huggingface dataset:
High-efficiency Transient Transduction of Human Embryonic Stem Cell–derived Neurons With Baculoviral Vectors
Authors: Jieming Zeng, Juan Du, Jiakai Lin, Xiao Ying Bak, Chunxiao Wu, Shu Wang
Journal: Molecular Therapy (2009)

Transient genetic manipulation of human neurons without chromosomal integration of the transgene would be valuable but has been challenging due to the quiescent nature of these postmitotic cells. In this study, we developed a set of baculoviral vectors for transient transduction in nondividing neurons derived from human embryonic stem cells (hESCs). Using a baculoviral vector equipped with the woodchuck hepatitis virus posttranscriptional regulatory element (WPRE), we observed a quick onset of transgene expression as early as day 1 after baculoviral transduction and a high efficiency of up to 80%. Strong transgene expression in the cultured human neurons was observed for more than 1 month and the signal was easily detectable even after 3 months. Using two baculoviral vectors carrying different transgenes, we found that co-transduction at a single neuron level was possible. After transplantation into the brain of nude mice, the baculovirus-transduced human neurons were integrated into the mouse brain and maintained transgene expression for at least 4 weeks, portending the usefulness of this technique in assisting neural transplantation. Therefore, by mediating efficient transient gene expression, baculoviral vectors can provide useful tools for both basic gene function studies in human neurons and therapeutic applications of these cells.
Ulcerative Colitis: A Clearer Picture
Authors: HARVEY J. DWORKEN
Journal: Annals of Internal Medicine (1983)

Editorials1 November 1983Ulcerative Colitis: A Clearer PictureHARVEY J. DWORKEN, M.D.HARVEY J. DWORKEN, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-99-5-717 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPhysicians who treat large numbers of patients with chronic ulcerative colitis in primary and secondary care settings know intuitively that this disorder does not usually have as grave a prognosis as published statistics indicate. This is not to say that many patients do not have periodic discomfort, that they do not require medication or slight alterations in their lifestyle, or indeed that a few patients may have severe colitis or require colectomies. However, most patients do, for the most part, respond well to therapy, avoid serious complications, require few if any hospitalizations, and lead long and productive lives.It is...References1. SINCLAIRBRUNTMOWAT TPN. Nonspecific proctocolitis in northeastern Scotland: a community study. Gastroenterology. 1983;85:1-11. CrossrefMedlineGoogle Scholar2. EDWARDSTRUELOVE FS. The course and prognosis of ulcerative colitis. Gut. 1963;4:299-315. CrossrefMedlineGoogle Scholar3. CELLO J. Ulcerative colitis. In: SLEISINGER MH, FORDTRAN JS, eds. Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. 3rd ed. Philadelphia: W. B. Saunders Company; 1983:1122-68. Google Scholar4. LINDÉNMÖLLER GC. Ulcerative colitis in Finland: II. One-year incidence in all hospitals. Dis Colon Rectum. 1971;14:264-6. CrossrefMedlineGoogle Scholar5. BONNEVIERIISANTHONISEN OPP. An epidemiological study of ulcerative colitis in Copenhagen county. Scand J Gastroenterol. 1968;3:432-8. CrossrefMedlineGoogle Scholar6. KATZKABRODYMORRISKATZ IRES. Assessment of colorectal cancer risk in patients with ulcerative colitis: experience from a private practice. Gastroenterology. 1983;85:22-9. CrossrefMedlineGoogle Scholar7. GREENSTEINSACHARSMITH ADH. Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology. 1979;77:290-4. CrossrefMedlineGoogle Scholar8. YARDLEYRANSOHOFFRIDDELLGOLDMAN JDRH. Cancer in inflammatory bowel disease: how serious is the problem and what should be done about it? [Editorial]. Gastroenterology. 1983;85:197-200. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Case Western Reserve University University Hospitals Cleveland, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByDysplasia and Cancer Surveillance in Inflammatory Bowel Disease 1 November 1983Volume 99, Issue 5Page: 717-718KeywordsColectomyColitisHospitalizationsUlcerative colitis Issue Published: 1 November 1983 PDF DownloadLoading ...
Determination of coronary flow reserve by parametric imaging.
Authors: O M Hess, M J McGillem, S F DeBoe, I M Pinto, K P Gallagher, G B Mancini
Journal: Circulation (1990)

Nine mongrel dogs were instrumented with electromagnetic flow probes (EMF) to measure coronary blood flow through the left anterior descending (LAD) and left circumflex (LCx) coronary arteries at rest and after maximal coronary vasodilation (1 mg/kg/min adenosine). Relative coronary blood flow was determined by parametric imaging in the left posterior oblique projection using digital subtraction angiography (DSA). Transmural myocardial perfusion of the LAD and LCx beds was determined with tracer-labeled microspheres. Coronary flow reserve (maximal coronary blood flow divided by resting blood flow) was calculated under control conditions and after constriction of the proximal LAD or LCx by a screw occluder. Heart rate decreased significantly from 140 beats/min at rest to 122 beats/min after adenosine (p less than 0.001) and from 134 (rest) to 120 beats/min (adenosine; p less than 0.05) after coronary constriction. Peak systolic pressure was kept constant with an aortic constrictor. Left ventricular end-diastolic pressure increased significantly from 18 mm Hg at rest to 23 mm Hg (p less than 0.05) after coronary constriction. At baseline, coronary flow reserve was 4.2 with DSA, 3.8 with EMF, and 3.7 with microspheres; after coronary constriction, it was 2.6 (DSA), 1.9 (EMF), and 1.5 (microspheres) (all p less than 0.001 versus baseline). Coronary blood flow showed a good correlation between EMF and microspheres (r = 0.87, p less than 0.001), with a standard error of estimate (SEE) of 0.78 ml/g/min. Coronary flow reserve also showed a good correlation between EMF and microspheres (r = 0.82, p less than 0.001), with an SEE of 0.93. There was a moderate correlation between EMF and DSA (r = 0.68, p less than 0.001), with an SEE of 1.35 (40% of mean coronary flow reserve). The correlation coefficient between microspheres and DSA was 0.54 (p less than 0.01), with an SEE of 1.46 (39% of mean coronary flow reserve). The mean difference (accuracy) and standard deviation of difference (precision) were 0.2 +/- 1.0 between EMF and microspheres, -0.1 +/- 1.4 between EMF and DSA, and -0.6 +/- 1.7 between microspheres and DSA. We conclude that determination of coronary flow reserve by parametric imaging is associated with large variations that are greater than variations also inherent in the two reference techniques. Parametric imaging allows relatively accurate assessment of coronary flow reserve (small mean difference), but precision is low (large standard deviation of mean differences).(ABSTRACT TRUNCATED AT 400 WORDS)
98 A RANDOMISED PHASE II TRIAL OF A DRUG ELUTING BEAD IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA BY TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION
Authors: R. Lencioni, K. Malagari, T. Vogl, F. Pilleul, A. Denys, A. Watkinson, J. Lammer
Journal: Journal of Hepatology (2009)
Report questions use of arsenic compound for leukaemia
Authors: S. Gottlieb
Journal: BMJ (2001)

A new report has raised questions about the safety of arsenic trioxide, a compound recently approved in the United States for treating acute promyelocytic leukaemia, a rare subtype of acute myelogenous leukaemia.

In a study of 10 patients who had leukaemia that had relapsed or had not responded to conventional treatment and who were taking arsenic trioxide, three died suddenly, researchers reported ( Blood 2001;98:266-71).

Even though the compound may provide benefits to some patients with leukaemia, “arsenic trioxide may be significantly, …
Prediction of early death after therapeutic hepatic arterial embolisation.
Authors: J Powell-Tuck, J McIvor, K W Reynolds, I M Murray-Lyon
Journal: BMJ (1984)

A consecutive series of 14 patients with hepatic malignant disease treated by palliative hepatic arterial embolisation was reviewed. Twelve patients had hepatic pain from their tumour and two were suffering from the carcinoid syndrome. Six patients died within four weeks of the procedure (group 1) and eight survived for at least 10 weeks (group 2). Factors were sought that might permit prediction of a high risk of early death (group 1). The pre-embolisation angiograms reviewed by a "blind" observer showed no differences in vascularity or tumour size between the groups and no difference in the extent of arterial occlusion after embolisation. The portal vein was patent in all patients. No significant difference was seen between the groups in the pre-embolisation biochemical values, with the exception of lower serum albumin concentrations and higher alkaline phosphatase activities in group 1. All those who died early had serum alkaline phosphatase activities of 45 KAU or above, while six of the eight who survived longer had activities below this value (p less than 0.02). These findings suggest that serum alkaline phosphatase activity of 45 KAU or more (normal range 3-13) might alone be a useful predictor of early death. Stepwise discriminant analysis using a weighted combination of serum alkaline phosphatase activity and albumin concentration predicted the outcome in all but one of the patients studied (p less than 0.002).
Abstract 3126: Renca RCC syngeneic model to evaluate efficacy of novel antisense oligonucleotides targeting TGF-β isoforms
Authors: Hanna Korhonen, Julie-Orlane Redon, Damien France, Guillaume Serin, Francis Bichat, Frank Jaschinski, Katja Wosikowski, Michel Janicot
Journal: Cancer Research (2014)

Abstract Transforming growth factor beta (TGF-β represents a family of cytokines, which function as the primary mediators for TGF-β signaling via TGF-β receptor type II (TβIIR) and both non-canonical and canonical downstream signaling pathways. TGF-β is associated with a wide range of biological processes in oncology, including tumor cell invasion, migration, angiogenesis, immunosuppression, as well as regulation of tumor stem cell properties. Hence, optimal preclinical evaluation of efficacy of TGF-β antagonists is challenging. Isarna Therapeutics has designed and developed selective and potent LNA-modified antisense oligonucleotides targeting the various TGF-β isoforms. In order to adequately evaluate selected preclinical development candidates, Oncodesign has developed customized experimental Renca tumor models in syngeneic and/or immunodeficient mice. The Renca cell line was established from a murine transplantable renal adenocarcinoma of spontaneous origin, and has been used under various experimental conditions: (1) subcutaneous tumor model by inoculating cells into the flanks of the animals; (2) the pulmonary metastatic tumor model by an intravenous injection of cells into the tail vein; and (3) the orthotopic tumor model by injecting cells into the renal subcapsule (and subsequent pulmonary metastasis). Outcome of this development program and preliminary results for selected TGF-β antisense oligonucleotides will be presented and discussed. Citation Format: Hanna Korhonen, Julie-Orlane Redon, Damien France, Guillaume Serin, Francis Bichat, Frank Jaschinski, Katja Wosikowski, Michel Janicot. Renca RCC syngeneic model to evaluate efficacy of novel antisense oligonucleotides targeting TGF-β isoforms. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3126. doi:10.1158/1538-7445.AM2014-3126
Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden
Authors: Khalid Abubaker, Ardian Latifi, Rod Luwor, Simon Nazaretian, Hongjian Zhu, Michael A Quinn, Erik W Thompson, Jock K Findlay, Nuzhat Ahmed
Journal: Molecular Cancer (2013)

Abstract Over 80% of women diagnosed with advanced-stage ovarian cancer die as a result of disease recurrence due to failure of chemotherapy treatment. In this study, using two distinct ovarian cancer cell lines (epithelial OVCA 433 and mesenchymal HEY) we demonstrate enrichment in a population of cells with high expression of CSC markers at the protein and mRNA levels in response to cisplatin, paclitaxel and the combination of both. We also demonstrate a significant enhancement in the sphere forming abilities of ovarian cancer cells in response to chemotherapy drugs. The results of these in vitro findings are supported by in vivo mouse xenograft models in which intraperitoneal transplantation of cisplatin or paclitaxel-treated residual HEY cells generated significantly higher tumor burden compared to control untreated cells. Both the treated and untreated cells infiltrated the organs of the abdominal cavity. In addition, immunohistochemical studies on mouse tumors injected with cisplatin or paclitaxel treated residual cells displayed higher staining for the proliferative antigen Ki67, oncogeneic CA125, epithelial E-cadherin as well as cancer stem cell markers such as Oct4 and CD117, compared to mice injected with control untreated cells. These results suggest that a short-term single treatment of chemotherapy leaves residual cells that are enriched in CSC-like traits, resulting in an increased metastatic potential. The novel findings in this study are important in understanding the early molecular mechanisms by which chemoresistance and subsequent relapse may be triggered after the first line of chemotherapy treatment.
Immediate effect of contrast medium injection on left ventricular volumes and ejection fraction. A study using metallic epicardial markers.
Authors: D L Vine, T D Hegg, H T Dodge, D K Stewart, M Frimer
Journal: Circulation (1977)

The immediate effect of contrast medium injection on left ventricular (LV) volume, stroke volume (SV) and ejection fraction (EF) was evaluated from postoperative LV biplane cineangiograms of 10 patients with 4-6 epicardial markers placed at the time of coronary artery surgery. After calibrating marker distances with respect to volume (r = 0.97-0.99) over one cardiac cycle for each patient, regression equations were used to compute LV volume from marker measurements for beats prior to, during and following injection. End-diastolic volumes (EDV) prior to injection ranged from 93-263 ml and did not change significantly with injection. End-systolic volumes (ESV) showed a mean decrease of 7.3 ml by beat 7 following injection; this was of borderline significance. Similarly, there was no significant change of SV or EF until beat 7 when there were small but significant increases of 6.4 ml and 0.04, respectively. The injection of moderate amounts of contrast in man does not cause significant changes in LV volume or EF through the sixth post-injection beat.
Panic Disorder Associated with Mitral Valve Prolapse: Psychosomatic Implications
Authors: Adam J. Krakowski
Journal: Psychotherapy and Psychosomatics (1987)

Findings of the second part of the clinical study initiated in 1982 are presented. Both aimed to determine possible clinical differences among panic disorder, agoraphobia with panic attacks and mitral valve prolapse syndrome (MVPS). Such clinical psychiatric differences could be useful because MVPS poses potentially dangerous consequences in patients with a high rate of serious cardiac and neurological complications. The first part of the study included 35 patients, 20 of whom were confirmed MVPS. This group appeared distinguishable by the increased frequency of fear of doing something uncontrolled and, even more so, by the anger-rage symptoms manifested during the attacks. In the present study of 100 patients, 36 of whom were documented MVPS, fear of doing something uncontrolled was not greater, although attacks of anger and rage were again higher than in the other two groups and exceeded 5% standard deviation. In all other psychological dimensions, the three groups did not differ from one another. This paper considers possible causes and consequences of symptoms seen in the MVPS.
Role of endothelins and nitric oxide in hepatic reperfusion injury in the rat
Authors: Benedikt H. J. Pannen, Ferid Al-Adili, Michael Bauer, Mark G. Clemens, Klaus K. Geiger
Journal: Hepatology (1998)

We determined the functional role of nitric oxide (NO) and endothelins (ET), two potent vasoactive mediator systems in the liver, for the pathogenesis of sinusoidal perfusion failure and lethal hepatocyte injury after low-flow ischemia/reperfusion in the isolated perfused rat liver. NO synthase blockade with Nω -nitro- l -arginine methyl ester ( l -NAME) (10 −3 mol/L) before reperfusion prevented increased NO 2 − /NO 3 − , the final products of NO oxidation, which could be observed in the vehicle group. Epifluorescence microscopy revealed that the decrease in functional sinusoid density during reperfusion was much more profound compared with vehicle. This was associated with a lower surface PO 2 , a substantially higher number of nonviable hepatocytes, as assessed by in situ propidium iodide staining, and enhanced enzyme release into the perfusate compared with vehicle. In contrast, reperfusion in the presence of the endothelin A+B receptor antagonist bosentan (2 × 10 −4 mol/L) restored functional sinusoid density and surface PO 2 to baseline values, resulted in a small reduction in the number of propidium iodide-positive hepatocytes, and caused similar increases in enzyme release as compared with vehicle. This indicates that hepatic generation of NO attenuates sinusoidal perfusion failure and improves liver tissue oxygenation, thus limiting hepatocyte injury during early reperfusion after hepatic low-flow ischemia. In contrast, endothelins counteract the microcirculatory effects of NO, i.e., mediate the no-reflow in hepatic sinusoids; however, the restoration of functional sinusoid density with bosentan resulted only in a small reduction in tissue damage, suggesting that additional components, which are independent of microcirculatory failure, contribute to hepatic reperfusion injury under these conditions.
Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2–dependent prostaglandin E2 in human dendritic cells
Authors: Jamma Trinath, Pushpa Hegde, Meenu Sharma, Mohan S. Maddur, Magalie Rabin, Jean-Michel Vallat, Laurent Magy, Kithiganahalli N. Balaji, Srini V. Kaveri, Jagadeesh Bayry
Journal: Blood (2013)
Australian regulator insists on greater transparency of industry payments to doctors
Authors: A. Coopes
Journal: BMJ (2014)

The Australian Competition and Consumer Commission has called for stricter transparency provisions in Medicines Australia’s new code of conduct that would prevent drug companies from making payments to doctors without prior consent to disclose them in full. Medicines Australia represents the country’s drug industry. 

The commission granted conditional approval for the new code, which will govern Australia’s self regulating drug sector for the next five years, on 17 October. But it ruled that Medicines Australia had not gone far enough in its reporting framework for sponsorship, speaking, or other fees paid to doctors.

Medicines Australia had proposed disclosure of payments only when the doctor in question consented to the information being made public. …
Desquamative esophagitis due to pemphigus vulgaris
Authors: Y. Matunaga, A. Goto, K. Fujii, H. Nakamura, M. Itoh, H. Wakasugi, K. Suzuki, K. Yonezawa, T. Abe, Y. Shinomura
Journal: Endoscopy (2010)

A 48-year-old woman was admitted to our hospital with hematemesis that occurred after dinner. Two years previously, she had been diagnosed as having pemphigus vulgaris on the basis of bullous lesions in the oral mucosa and the presence of anti-desmoglein 3 (Dsg3) antibodies. Esophagogastroduodenoscopy (EGD) revealed desquamation of the mucosa, blood oozing from the entire esophagus ([Fig. 1]), and a whitish strip, which was exfoliated esophageal mucosa, hanging loosely from the cardia ([Fig. 2]). Prednisolone (30 mg/day) was administered. Two weeks later, EGD showed a dramatic improvement in the esophageal mucosa, which had an almost normal appearance ([Fig. 3]).
XVIII. Medical Education: The Problems Intensify
Authors: Lester S. King
Journal: JAMA (1983)

By 1893 the American medical profession resembled the little girl in the nursery rhyme who, when good, was very very good, but "when she was bad she was horrid." American physicians might be among the best or among the worst in the world. According to one author, some might be "easily placed among renowned and successful" while others have made the American physicians "to be a by-word and a reproach."<sup>1</sup>The depths of badness we noted last month. To improve the general level of practice was extremely difficult. A physician might easily remain active for 40 years or more. If he was not very good to begin with, he did not ordinarily improve. There was thus a large backlog of poorly trained physicians in active practice. Nevertheless, improvements in medical education did bring hope, which centered especially on the new generation. At the end of the 1890s medical educators
Diseases of the respiratory system.
Authors: J W Todd
Journal: BMJ (1978)

ulcer has shown that admission for perforation in the years 1973-6 was as common among black as among white patients at the Johannes- burg General Hospital.'The type of complica- tion occurring was also similar in the two population groups, perforation and haemorrhage being common, in contrast to the greater frequency of stenosis reported in many studies from rural areas in Africa.
Development and Validation of a Risk Score for Predicting Death in Chagas' Heart Disease
Authors: Anis Rassi, Anis Rassi, William C. Little, Sérgio S. Xavier, Sérgio G. Rassi, Alexandre G. Rassi, Gustavo G. Rassi, Alejandro Hasslocher-Moreno, Andrea S. Sousa, Maurício I. Scanavacca
Journal: New England Journal of Medicine (2006)

Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death in patients with Chagas' heart disease.
Focus on Specialty Hospitals
Authors: Mike Mitka
Journal: JAMA (2008)

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