tbuckley/cabot-search huggingface dataset:
677. Generation and Application of an Efficient Chronic Myelogenous Leukemia (CML)-Targeted Recombinant Adeno-Associated Virus (rAAV) Vector: New Therapeutic Options?
Authors: Marlon R. Veldwijk, Marius Stiefelhagen, Juergen A. Kleinschmidt, Anna Jauch, Stephanie Laufs, Frederik Wenz, W. Jens Zeller, Stefan Fruehauf
Journal: Molecular Therapy (2006)

Top of pageAbstract
Introduction: Despite great advances in vector development, most standard rAAV-2 vectors still lack the target cell specificity required for an efficient in vivo application. In addition, the gene transfer efficiency in many promising target cells (e.g.: peripheral blood progenitor cells (PBPC)) is low. Thus, designing gene therapy protocols for diseases like chronic myelogenous leukemia (CML) remained difficult, as standard rAAV-2-based vectors lack both the required gene transfer efficiency and selectivity. A recent advancement in vector development (Muller et al., 2003) now allows the generation of rAAV capsid mutants that offers higher target cell specificity and transduction efficiency. This method was applied to obtain a CML-targeted rAAV vector and was tested on a panel of leukemic cell lines, as well on primary CML material.

Material and Methods: Performing latter method on the CML cell line K562 (4 selection rounds), several mutant CML-targeted rAAV2 capsid clones were obtained, cloned into an rAAV2 helper plasmid and for each of the mutants rAAV2-eGFP vector stocks were produced. Titers were verified using our real time PCR-based titration assay. To determine efficiency and specificity, a panel of leukemic (CML and AML) and non-leukemic cell lines, as well primary human CML and PBPC cells were transduced with these vectors. Mock, normal rAAV2 and random mutant clone-transduced cells served as controls. Transduction of primary human CML and PBPC cells was confirmed using FACS-sorted GFP+ cells with subsequent bcr-abl-FISH or FACS analysis for GFP/CD34+ co- expression, respectively.

Results: Transduction of a panel of six leukemic cell lines with the CML-targeted rAAV2 vectors (moi 100 iu) resulted in an over 10-fold increase of gene transfer efficiency compared to random mutant and standard rAAV2 vectors; gene transfer rates of >60% were obtained. In primary human cells, for both CML (n=4) and PBPC (n=2), an increase in gene transfer was observed (CML: AAV2: 2.4 |[plusmn]| 0.2 vs AAV2-cml: 5.1 |[plusmn]| 1.6 (p=0.04). CD34+: AAV2: 3.2 |[plusmn]| 0.9 vs AAV2-cml: 8.5 |[plusmn]| 4.3 (p>0.05)). All transduced cell were positive for either the BCR-ABL fusion gene (CML) or the PBPC marker CD34. In contrast, gene transfer of the mutant CML-targeted rAAV2 vectors into non-leukemic cell lines resulted in a reduction in gene transfer efficiency compared to standard rAAV2 vectors (<50%).

Conclusion: In this study, we were able to generate a CML-targeted rAAV2 vector, which was able to transduce leukemic cell lines and primary human CML cells with significant higher efficiency and specificity than standard rAAV2 vectors. The development of these vectors holds promise for future clinical applications.
Surface-induced changes in protein adsorption and implications for cellular phenotypic responses to surface interaction
Authors: Lorcan T. Allen, Miriam Tosetto, Ian S. Miller, Darran P. O’Connor, Stephen C. Penney, Iseult Lynch, Alan K. Keenan, Stephen R. Pennington, Kenneth A. Dawson, William M. Gallagher
Journal: Biomaterials (2006)
A SEASONAL DERMATITIS CAUSED BY SYNERGIC INFECTION
Authors: A. J. Brier
Journal: JAMA (1934)

<h3>History.</h3> A boy, aged 15 years, in the early part of 1933 was referred to one of us (A. J. B.) for dermatitis, which was thought to be an allergic manifestation. The onset was described as being somewhat acute, having begun five or six years before with primary lesions, starting in the interdigital spaces as groups of blisters and rapidly becoming pustular. It was reported that this followed a day spent in playing along the bank of a creek known to be polluted with sewage. The lesions appeared in "crops," undergoing their metamorphosis while others were forming. Early in their existence the vesicles contained a clear, colorless, serous fluid before they became pustules. This sequence continued; new vesicles formed as the pustules healed. The patient's hands became unsightly, causing him much mental as well as physical discomfort, since his hands itched and were very sore during an exacerbation of the
ANALGESIA IN CHILDBIRTH
Authors: A. Z. C. Cressy
Journal: BMJ (1930)

“Evidence based medicine” (EBM) is often seen as a scientific tool for quality improvement, even though its application requires the combination of scientific facts with value judgments and the costing of different treatments. How this is done depends on whether we approach the problem from the perspective of individual patients, doctors, or public health administrators. Evidence based medicine exerts a fundamental influence on certain key aspects of medical professionalism. Since, when clinical practice guidelines are created, costs affect the content of EBM, EBM inevitably becomes a form of rationing and adopts a public health point of view. This challenges traditional professionalism in much the same way as managed care has done in the US. Here we chart some of these major philosophical issues and show why simple solutions cannot be found. The profession needs to pay more attention to different uses of EBM in order to preserve the good aspects of professionalism.
Care of the Wounded in Vietnam
Authors: Alvin M. Cotlar
Journal: JAMA (1989)

Historically, at least through the Korean War, primitive initial battlefield treatment measures, delays and inefficiencies of transport, and nonavailability of effective drugs and resuscitative equipment limited the application of clinical wartime experience to civilian medicine. Vietnam, however, provided a wealth of data that can be effectively used in improving modern battlefield medicine as well as in managing civilians with traumatic injuries. This results from the absence of front lines and variation from the traditional chain of evacuation in Southeast Asia. Helicopter operations in Vietnam were revolutionary, and often patients arrived at a definitive care facility in less than an hour. Retired Brigadier General Hardaway begins his book with a review of the approach to battlefield shock from World War I through Vietnam, describing the rapid and sophisticated resuscitative measures used in Southeast Asia. He gives an overview of the medical care system as it existed in Vietnam early in the
Mortality Associations with Long-Term Exposure to Outdoor Air Pollution in a National English Cohort
Authors: Iain M. Carey, Richard W. Atkinson, Andrew J. Kent, Tjeerd van Staa, Derek G. Cook, H. Ross Anderson
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Cohort evidence linking long-term exposure to outdoor particulate air pollution and mortality has come largely from the United States. There is relatively little evidence from nationally representative cohorts in other countries.
Pertussis IgE and atopic disease
Authors: L. Nilsson, C. Grüber, M. Granström, B. Björkstén, N.‐I. M. Kjellman
Journal: Allergy (1998)

Background Pertussis toxin (PT) stimulates IgE production in animals, and pertussis vaccination and whooping cough may have similar effects in man. Methods We analyzed IgE responses to PT (FT‐IgE) in sera from children primarily immunized with three doses of either an acellular 2‐ or 5‐component vaccine, or a whole‐cell (We) pertussis vaccine, and in children after whooping cough. The study comprised 50 children with both atopic disease and positive skin prick test, 99 nonatopic controls, and 40 children with verified pertussis. Results Immunoglobulin E antibodies against PT were demonstrated in 19% and 24% of sera from vaccinated children at 7 and 12 months, respectively, and in 9% at 2.5 years. At 7 months, PT‐IgE was more common after vaccination with acellular (24%) than with the We vaccine (3%, P = 0,02), PT‐IgE was also more common (P = 0.00l) after vaccination in children classified as atopic (36%) than in the control group (10%). Thirty percent of the children with pertussis had PT‐IgE, more often so in atopic than nonatopic children (P = 0.02), Conciusions Transient production of PT‐lgE seems to be common after primary pertussis immunization with acellular vaccines, and after whooping cough, particularly in atopic subjects.
Abstract 3619: The absence of cleaved caspase-3 in circulating tumor cells detected using a non-enrichment-based assay
Authors: Thomas J. Metzner, Kelly Bethel, Edward H. Cho, Madelyn S. Luttgen, Daniel C. Lazar, Maria L. Uson, Jorge J. Nieva, Lyudmila Bazhenova, Anand Kolatkar, Peter Kuhn
Journal: Cancer Research (2012)

Abstract Background: The role of cleaved caspase-3 as an integral player in the apoptotic process of mammalian cells has prompted the investigation of an assay to detect cleaved caspase-3 in circulating tumor cells (CTCs) as one way to assess CTC viability. Methods: Using a previously developed non-enrichment based assay, nucleated blood cells and CTCs are adhered to a single slide. An antibody for cleaved caspase-3 was incorporated into the assay in addition to the existing antibodies for cytokeratin (to identify tumor cells) and CD45 (to identify white blood cells), as well as a nuclear stain (DAPI). The modified assay was initially tested on cultured MCF 10a cells spiked into normal donor blood. Before spiking, apoptosis was induced in these cells using staurosporine. Following validation of the assay in cell lines, the assay was performed using blood samples from 9 different breast cancer patients, as well as 3 different normal donor samples. Results: CTCs were detected in the patient samples as single cells, as well as clusters. The results of the assay showed that only 1 out of 896 detected CTCs was positive for cleaved caspase-3 (0.11%). Of these CTCs, 134 of them were found to be in clusters, and all 134 were negative for cleaved caspase-3, indicating that whether in clusters or as single cells, the vast majority of CTC's detected with this assay are not undergoing irreversible apoptotic processes via cleaved caspase-3. The results also showed that 0.40% of white blood cells in healthy donors expressed cleaved caspase-3, compared to 0.51% of the white cells in cancer patients, indicating that healthy donors and cancer patients express cleaved caspase-3 in their white blood cells at nearly the same rate. Conclusions: The morphologic characterization used in this platform to select healthy-appearing cells identifies a population of circulating tumor cells with virtually no evidence of caspase-related ongoing apoptosis, a finding that supports the morphologic impression of viability. 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 3619. doi:1538-7445.AM2012-3619
Culture of Trichomonas vaginalis
Authors: B. M. Wilkinson, G. C. J. Williams
Journal: BMJ (1958)

JOUMNA COMMENTTwelve cases of dermatitis herpetiformis were treated with sulphamethoxypyridazine; one of them was of a seyere bullous type and four were of the juvenile variety.Response in all these cases was most satisfactory.Several patients who had already received the usual controls for the disease declared spontaneously that the present treatment was the most pleasant and the most effective.One adult and three juvenile patients remained well after cessation of treat- ment.
Acoustic Propagation Properties of Normal, Stunned, and Infarcted Myocardium
Authors: William D. O’Brien, Kiran B. Sagar, David C. Warltier, Theodore L. Rhyne
Journal: Circulation (1995)

Background Identification of viable but stunned myocardium remains a major problem. Since stunned myocardium results in impairment of myocardial function without any structural damage and infarcted myocardium causes major structural disruption, we postulated that acoustic properties could distinguish between the two insults. Methods and Results Anesthetized open-chest dogs underwent a total occlusion of the left anterior descending coronary artery for 15 minutes (stunned, n=7) and 90 minutes (infarcted, n=8), followed by reperfusion for 3 hours. Circumflex coronary artery perfusion territory (n=15) served as normal control tissue. Regions of myocardium were quantitatively evaluated with a scanning laser acoustic microscope operating at 100 MHz and a research ultrasound system operating at 4 to 7 MHz. Four ultrasonic parameters were determined: attenuation coefficient (an index of loss per unit distance), speed of propagation, a spatial variation of propagation speed called the heterogeneity index (HI), and ultrasonic backscatter at 5 MHz (IBR5). Myocardial water, lipid, and protein contents of normal, stunned, and infarcted myocardium were also determined. The attenuation coefficient of normal myocardium (179±20 dB/cm) was significantly greater than that of stunned (136±7 dB/cm, P &lt;.001) and infarcted (130±8 dB/cm, P &lt;.001) myocardium. The propagation speed of normal myocardium (1597±6 m/s) was similar to that of stunned (1600±6 m/s) and significantly higher than that of infarcted (1575±7 m/s, P &lt;.001) myocardium. The HI for specimen thicknesses of 75 to 100 μm showed an increase of 33% between normal (5.0±0.8 m/s) and stunned (7.5±2.3 m/s, P &lt;.05) myocardium. However, for the infarcted myocardium (5.8±2.0 m/s), the HI was essentially the same as that of the normal myocardium (5.0±0.8 m/s). The IBR5 of normal (−47.1±1.0 dB) was not significantly different from that of stunned myocardium (−46.8±0.9 dB). The IBR5 of infarcted myocardium (−42.4±1.0 dB) was significantly greater than that of normal myocardium. Myocardial water and protein contents were similar in the normal and stunned myocardium. Water content in the infarcted myocardium (80.8±2%) was significantly greater ( P &lt;.05) than in the normal (72.7±1.3%), and protein content of 18.5±0.7% was significantly lower ( P &lt;.05) than the normal (21.4±0.8%). Lipid content was increased in the stunned (8.5±0.5%) and virtually absent in the infarcted myocardium (0.8±0.3%) compared with normal (5.5±0.6%). Conclusions We conclude that acoustic propagation properties can identify stunned and infarcted myocardium and may be related to biochemical/morphological differences.
Coenzyme A Reductase Inhibitors and Stroke
Authors: Heiner C. Bucher
Journal: Annals of Internal Medicine (1998)

Letters15 July 1998Coenzyme A Reductase Inhibitors and StrokeHeiner C. Bucher, MD, MPH, Lauren E. Griffith, MS, and Gordon H. Guyatt, MD, MScHeiner C. Bucher, MD, MPHMedizinische Universitats-Poliklinik; CH-4031 Basel, SwitzerlandMcMaster University; Hamilton, Ontario L8N 3Z5, CanadaSearch for more papers by this author, Lauren E. Griffith, MSMedizinische Universitats-Poliklinik; CH-4031 Basel, SwitzerlandMcMaster University; Hamilton, Ontario L8N 3Z5, CanadaSearch for more papers by this author, and Gordon H. Guyatt, MD, MScMedizinische Universitats-Poliklinik; CH-4031 Basel, SwitzerlandMcMaster University; Hamilton, Ontario L8N 3Z5, CanadaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-129-2-199807150-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Crouse wonders why we did not include seven additional trials of HMGcoA reductase inhibitors in our analysis. These trials did not report the number of strokes that occurred, so the requisite information for our analysis was not available. Dr. Crouse hypothesizes that the strong effect observed occurred because more of the HMGcoA studies are secondary prevention trials. Two meta-analyses analyzing the effects of HMGcoA inhibitors that have been published since our overview [1, 2] have found similar odds ratios with large, overlapping confidence intervals for the primary and secondary prevention trials involving HMGcoA reductase inhibitors. These data ...References1. Hebert PR, Gaziano JM, Chan KS, Hennekens CH. Cholesterol lowering with statin drugs, risk of stroke, and total mortality. JAMA. 1997; 278:313-21. Google Scholar2. Crouse JR III, Byington RP, Hoen HM, Furberg CD. Reductase inhibitor monotherapy and stroke prevention. Arch Intern Med. 1997; 157:1305-10. Google Scholar Author, Article, and Disclosure InformationAffiliations: Medizinische Universitats-Poliklinik; CH-4031 Basel, SwitzerlandMcMaster University; Hamilton, Ontario L8N 3Z5, Canada PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1998Volume 129, Issue 2Page: 162KeywordsCoenzymesConfidence intervalsOdds ratioStroke Issue Published: 15 July 1998 CopyrightCopyright © 1998 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
ENDOTHELIAL FUNCTION AND PLATELET REACTIVITY IN PATIENTS AFTER PERCUTANEOUS CORONARY INTERVENTION: THE IMPACT OF CLOPIDOGREL, PRASUGREL AND TICAGRELOL
Authors: Gerasimos Siasos, Eleni Kokkou, Dimitris Tousoulis, Stamatios Kioufis, Evangelos Oikonomou, Marina Zaromitidou, Konstantinos Maniatis, Savvas Mazaris, Theodosia Konsola, Manolis Vavuranakis, Nikolaos Papageorgiou, Panagiotis Tourikis, Christina Kollia, Christodoulos I. Stefanadis
Journal: Journal of the American College of Cardiology (2014)
Hyperamylasemia: Beacon or Siren?
Authors: J. EDWARD BERK
Journal: Annals of Internal Medicine (1974)

Editorial Notes1 May 1974Hyperamylasemia: Beacon or Siren?J. EDWARD BERK, M.D., F.A.C.P.J. EDWARD BERK, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-80-5-665 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAmylase is a fascinating and challenging enzyme. Arising from sources still not entirely clear, it apparently circulates in the blood only to exit in the urine or to be destroyed in sites not yet fully identified. Though long used as a clinical marker of pancreatic abnormality, the diagnostic value of elevated serum amylase activity is hampered by shortcomings in current knowledge. Not only is the degree of change of serum amylase unpredictable, but its seemingly perverse and capricious behavior often creates a diagnostic dilemma.Hyperamylasemia is notoriously short-lived in most cases of acute pancreatitis and occurs only infrequently in patients...References1. JANOWITZDREILING HD: Plasma amylase: source, regulation and diagnostic significance. Am J Med 27:924-935, 1959 CrossrefMedlineGoogle Scholar2. KNIGHTWILLIAMSELLIS ADG: Significance of hyperamylasemia and abdominal pain in diabetic ketoacidosis. Br Med J 3:128-131, 1973 CrossrefMedlineGoogle Scholar3. BLOCKBERKFRIDHANDLER MJL: Diabetic ketoacidosis associated with mumps virus infection. Occurrence in a patient with macroamylasemia. Ann Intern Med 78:663-667, 1973 LinkGoogle Scholar4. BERKKIZUWILDING JHP: Macroamylasemia: a newly recognized cause for elevated serum amylase activity. N Engl J Med 277:941-946, 1967 CrossrefMedlineGoogle Scholar5. BERKFRIDHANDLERMONTGOMERY JLK: Simulation of macroamylasemia by salivary-type ('S type') hyperamylasaemia. Gut 14:726-729, 1973 CrossrefMedlineGoogle Scholar6. AMMANNBERKFRIDHANDLER RJL: Hyperamylasemia with carcinoma of the lung. Ann Intern Med 78:521-525, 1973 LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Department of Medicine University of California Irvine, California PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByPhenformin and Hyperamylasemia in Lactic AcidosisLYDIA A. CONLAY, M.D., JOSEPH E. LOEWENSTEIN, M.D., F.A.C.P.The Human α-AmylasesPancreatic IsoamylasesMICHAEL E. ROSS, M.D., ROBERT O. WOLF, D.D.S. 1 May 1974Volume 80, Issue 5Page: 665-665KeywordsAcute pancreatitisBehaviorBiomarkersBloodEnzymesUrine Issue Published: 1 May 1974 PDF DownloadLoading ...
Intramuscular Iron Therapy in Anaemia of Pregnancy
Authors: J. M. Scott
Journal: BMJ (1956)

Since publishing a preliminary report on the treatment of the iron-deficiency anaemias of pregnancy with intra- muscular injection of iron (" imferon ") (Scott and Govan, 1954), we have continued to use this drug and can now review the results obtained in a series of 300 patients.In practice almost double that number have been treated in this hospital with imferon.Ultimately, however, many of these cases were discarded in the final analysis for various reasons, such as an inadequate period of observation, failure on the part of patients to co-operate, and the intervention of obstetrical complications.Of these patients, 200 had antenatal anaemia.Their average age was 30.9 years and average parity 4.1.When they were first seen at the blood clinic the mean duration of their pregnancies was 33.8 weeks (S.D.=5.3) and their average haemoglobin and red-cell count were 8.5 g. per 100 ml.(S.D.=0.9) and 3,370,000 per c.mm. respectively.In 156 the anaemia was of moderate degree (haemoglobin between 8 and 9.9 g./100 ml.), but in the remainder the readings were below 8 g. /100 ml.The second group of 100 patients were all post-natal.The majority had post-haemorrhagic anaemia and low haemoglobins and red-cell counts, the average being 8.3 g. /100 ml. and 2,760,000 per c.mm. respectively.These patients, unlike those with antenatal anaemias, did not belong solely to the older parous groups, their average age being 27.7 years and the parity 2.6.Venous blood was used for all haemotological investi- gations, and the haemoglobin estimations were made in a photoelectric colorimeter.The intramuscular iron was administered personally at the antenatal clinic, but