tbuckley/cabot-search huggingface dataset:
Abstract 2746: Microsomal prostaglandin E2 synthase-1 may provide a novel specific therapeutic target in neuroblastoma.
Authors: Anna Kock, Agnes Rasmuson, Marina Korotkova, Helena Idborg, John Inge Johnsen, Per-Johan Jakobsson, Per Kogner
Journal: Cancer Research (2013)

Abstract Background: Neuroblastoma (NB) cells are enriched in the omega-6 fatty acid arachidonic acid, the substrate for the cyclooxygenase (COX) enzymes and prostaglandin biosynthesis. The inducible isoform, COX-2 is overexpressed in NB and NB cells produce prostaglandin E2 (PGE2) that acts as an autocrine and/or paracrine survival and proliferation factor. Downstream of the COX enzymes, specific synthases are responsible for the production of the respective prostaglandins. Microsomal prostaglandin E2 synthase-1 (mPGES-1) specifically converts PGH2 to PGE2 and is thought to primarily couple to COX-2. The aim of this study was to investigate if inhibition of mPGES-1 could represent an alternative therapeutic approach to COX- inhibition in NB. Methods: Western blot and immunohistochemistry were used for protein detection. Cell viability of seven NB cell-lines treated with the mPGES-1 inhibitor CAY1052 was determined by MTT-assay. Stable mPGES-1 knockdown SK-N-BE2 clones were established using shRNA and the clonogenic capacity was analysed by clonogenic assay. To study the in vivo effect of COX inhibition, four week old homozygous TH-MYCN mice were treated with 10mg/L diclofenac for two weeks. Ex vivo analyses of COX-metabolites in tumors were performed by LC-MS/MS. Results: Expression of mPGES-1 in human NB tumors and in NB cell lines could be detected. Inhibition of mPGES-1 reduced NB cell growth in vitro and knockdown of mPGES-1 significantly reduced the clonogenic capacity. Expression of COX-1, COX-2 and mPGES-1 in TH-MYCN tumors could be detected and treatment with the dual COX-inhibitor diclofenac significantly reduced tumour weight, compared to untreated animals. Ex vivo analysis of tumor tissues from treated animals revealed a significantly decreased level of COX metabolites compared to controls. The expression of mPGES-1was not affected by the treatment. Furthermore, cells staining positive for cleaved caspase-3 were more prevalent in treated tumors indicating apoptosis Induction. Conclusion: We found that mPGES-1 is expressed in NB, with a potential role for PGE2 synthesis and tumor growth. mPGES-1 represents an alternative therapeutic target for inhibiting NB growth through specific PGE2 inhibition and the TH-MYCN model is well suited for in vivo studies with this purpose. Citation Format: Anna Kock, Agnes Rasmuson, Marina Korotkova, Helena Idborg, John Inge Johnsen, Per-Johan Jakobsson, Per Kogner. Microsomal prostaglandin E2 synthase-1 may provide a novel specific therapeutic target in neuroblastoma. [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 2746. doi:10.1158/1538-7445.AM2013-2746
Clinical Use of the Percutaneous Renal Biopsy
Authors: JOHN D. ARNOLD, BENJAMIN SPARGO
Journal: Circulation (1959)

The renal biopsy is undoubtedly a justifiable diagnostic tool though it has not yet reached full maturity in clinical practice. Risks. For most patients the risks do not appear to be excessive. An added caution must be exercised in malignant hypertension but even here after careful appraisal of this added risk the biopsy may still be justified. The experience of the operator would appear to modify some of the risk. Returns. The biopsy has often added to the confusion surrounding a given case because it may be uninterpretable or because it provides an unfamiliar complex of findings. Thisresult is becoming less common with increasing experience. Even when the histology of the kidney is not diagnostic, it may suggest something of clinical value about the nature of the disease process, such as the presence of vascular disease, focal nephritis, or tubular disease of unidentified nature. The use of the electron microscope has extended the range of the percutaneous biopsy considerably. It is unfortunate that the cost and complexity of this instrument have confined it to certain centers. It should be remembered also that a number of technical failures will occur, and the sampling error may be large. Despite these real problems, the percutaneous renal biopsy is often the only way of establishing a diagnosis and makes its greatest contribution in the appraisal of the asymptomatic patient with proteinuria and an abnormal urinary sediment.
Coordinating and Prioritizing Aid in Haiti
Authors: Louise C Ivers, Kimberly Cullen
Journal: New England Journal of Medicine (2010)

Now that there are many disaster-relief organizations on the ground in Haiti, it is critical that we coordinate efforts, both during this acute phase of the response and as we move forward. There is still an overwhelming number of patients who require advanced orthopedic care. These patients must be identified quickly and transported safely to the numerous operating rooms now in place in field hospitals. Lives and limbs are being lost with every bottleneck in the flow of aid — a major hitch being our limited ability to move patients. We might not have been able to predict this earthquake, . . .
Tumour necrosis factor-alpha increases extravasation of virus particles into tumour tissue by activating the Rho A/Rho kinase pathway
Authors: Takahiro Seki, Fionnadh Carroll, Sam Illingworth, Nicky Green, Ryan Cawood, Houria Bachtarzi, Vladimir Šubr, Kerry D. Fisher, Leonard W. Seymour
Journal: Journal of Controlled Release (2011)
Whittling: The Last Class
Authors: JOHN STONE
Journal: Annals of Internal Medicine (1979)

Ad Libitum1 December 1979Whittling: The Last ClassJOHN STONE, M.D.JOHN STONE, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-91-6-923_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptWhat has been writtenabout whittlingis not truemost of itIt is the discoverythat keepsthe fingers movingnot idlenessbut the knife looking forthe right planethat will let the secret outWhittling is no pastimehe sayswho has been whittlingin spare minutes at the woodof his life for forty yearsThree rules he thinkshave helpedMake small cuts.In this wayyou may be able to stop beforewhat was to be an armhas to be something elseAlways whittle away from yourselfand toward something.For God's sake... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Atlanta, Georgia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 December 1979Volume 91, Issue 6Page: 923-923 ePublished: 1 December 2008 Issue Published: 1 December 1979 PDF downloadLoading ...
Anaphylactoid Reaction to Single-Component Pork Insulin
Authors: Robert A. Goldman
Journal: JAMA (1976)

A PATIENT who initially exhibited local skin erythema to single-component pork insulin went into anaphylaxis during single-component pork insulin desensitization. <h3>Case Report</h3> A 47-year-old woman with a five-month history of severe local erythema surrounding sites of insulin injection was admitted to Hahnemann Hospital for insulin desensitization. She did well in the hospital and for about two weeks after discharge with beef-pork isophane insulin suspension, but then, severe erythema and induration developed at the sites of insulin administration. A change to pork insulin zinc suspension (Lente) was no better. Skin tests employing beef- and pork-regular insulins, as well as pork insulin zinc suspension showed positive skin responses at the lowest insulin dilutions (0.001 units). Desensitization was attempted with single-component regular pork insulin according to the protocol shown in the Table. The patient had been supported with 10 units of pork insulin at six hourly intervals for 24 hours prior to the
MILD FORMS OF OBSTRUCTIVE SLEEP APNEA ARE ASSOCIATED WITH SUBCLINICAL CORONARY ATHEROSCLEROSIS AMONG CLIMACTERIC WOMEN
Authors: Rodrigo Pinto Pedrosa, Ricardo Q. Coutinho, Isly M.L. Barros, Ana Kelley L. Medeiros, Ana Paula D.L. Leite, Marcio Bittencourt, Liana L. Carvalho, Martinha M.B. Carvalho, Thais C. Lustosa, Maria Priscila F. Lira, Willian A. Chalela, Moacir N.L. Ferreira, Laura O. B. F Costa
Journal: Journal of the American College of Cardiology (2014)
741. Self-Complementary Adeno-Associated Virus Vectors: Packaging Capacity and Purity
Authors: Jianqing Wu, Weihong Zhao, Li Zhong, Kenneth H. Warrington, Arun Srivastava
Journal: Molecular Therapy (2006)

Recombinant adeno-associated virus 2 (AAV) vectors are currently in use in Phase I/II clinical trials for the potential treatment of several diseases. However, the single-stranded nature of the AAV genome impacts on transgene expression from these vectors. Although self- complementary AAV (scAAV) vectors, which contain double- stranded genomes, and therefore bypass the requirement for viral second-strand DNA synthesis, lead to a significant increase in AAV- mediated transduction efficiency, the packaging capacity of these vectors ( 2.4 kb) is significantly smaller than the conventional AAV vectors (4.8 kb). In order to initially determine the maximum packaging capacity of scAAV vectors, we constructed GFP gene expression cassettes of various sizes ranging from 2.2 kb to 4.0 kb. Surprisingly, each of these genomes could be encapsidated into mature progeny virions with very similar titers. The transduction efficiency of vectors containing <3.3 kb genomes was significantly higher than those containing 3.5 kb genomes or larger. When encapsidated genomes from each of the vector stocks were analyzed on alkaline agarose gels, we observed that 45% of viral DNA was double- stranded, and 55% was still single-stranded in vectors containing up to 3.3 kb genomes, and 3.5 kb and larger genomes were packaged only as single-stranded DNA. These data suggest that the maximum packaging capacity of scAAV vectors is 3.3 kb. We also observed that double-stranded AAV genomes larger that 3.5 kb could be encapsidated into virions composed of only two capsid proteins VP1 and VP3. However, the ratio of single-stranded:double-stranded vectors was higher in VP1-VP3 capsids compared with the wild- type capsids. Each of these vectors containing up to 3.3 kb genomes was biologically active, and their transduction efficiencies were very similar. The generation of single-stranded genomes was due to the use of AAV helper plasmid that contains the Rep gene with an ATG start codon, known to lead to higher levels of expression of Rep proteins. We further examined the mechanism of production of single- stranded genomes. Following rescue and replication of AAV genomes and digestion with Msc I restriction endonuclease, we determined that the terminal resolution site (trs) in one of the inverted terminal repeats in the AAV genome was not repaired. We hypothesize that the presence of cryptic 'trs-like' sites in recombinant AAV genomes leads to the generation of single-stranded DNA. Taken together, these studies demonstrate that it is feasible to achieve encapsidation of larger genomes into scAAV vectors than was suggested originally, but also underscore the need to exercise caution in using the appropriate helper plasmid in order to generate purified preparations of scAAV stocks that are completely free of single-stranded DNA- containing vectors capable of high-efficiency transduction, which has implications in the optimal use of these vectors in human gene therapy.
Chancellor unveils "son of PFI" to build next generation of hospitals
Authors: I. Torjesen
Journal: BMJ (2012)

A new wave of hospitals will be built under a revamped version of the discredited private finance initiative (PFI) scheme, the chancellor of the exchequer, George Osborne, announced to the House of Commons in his autumn statement.

In a document published the same day outlining how the new public-private partnerships, to be known as PFI2, would work, the Treasury admitted that the existing PFI scheme had “become tarnished by its waste, inflexibility and lack of transparency.”1 Costly and inflexible PFI deals that tied trusts to expensive and inflexible contracts for many years have been blamed for the financial instability of at least 20 trusts.2

Osborne told MPs that the public sector had been “ripped off” by PFI schemes in the past. “The big difference is that from now on, instead of the public sector bearing the risk and getting none of the reward . . . it will share in the upside as well.”

“Soft” services such as cleaning and …
Homocystinuria due to cystathionine synthase deficiency: the metabolism of L-methionine.
Authors: L Laster, S H Mudd, J D Finkelstein, F Irreverre
Journal: Journal of Clinical Investigation (1965)

During surveys of mentally retarded patients for evidence of metabolic errors, investigators in Ireland (1) and in America (2) independently dis- covered that abnormal excretion of homocystine in the urine may accompany retardation.A syn- drome has since been defined (3-9) with the rela- tively constant clinical features of mental defi- ciency, fine, fair hair, dislocated ocular lenses, malar flush, peculiar gait, and genu valgum; and with the variable features of pes cavus, long ex- tremities and digits, convulsions, thrombotic in- cidents that have been attributed to abnormal stickiness of the platelets (10), cardiovascular dis- orders, and fatty liver.Almost without exception the patients have had elevated concentrations of methionine and homocystine in the blood plasma in addition to increased amounts of homocystine in the urine.A mentally retarded child, C.T., with many of the clinical and all of the biochemical abnormalities of the disorder, has been shown to lack detectable activity of cystathionine synthase I in her liver (12).This enzyme catalyzes a reaction involved in methionine metabolism (reaction 4, Figure 1), and we have proposed that deficiency of cystathionine synthase activity is the fundamental defect in the disease.The parents of C.T., who are free of clinical stigmata of the disease and who do not ex- crete abnormal amounts of homocystine in the urine, *
Thank You, Uncle Sam: Letters of a World War II Army Nurse From North Africa and Italy
Authors: Phyllis Wells
Journal: JAMA (1988)

Eugenia Kielar graduated from Temple University Hospital School of Nursing in 1942. Like so many other health care workers caught up in the patriotism of the war effort, she enlisted in 1943. This book is a collection of letters written to her parents during her two years of active duty. Through her chatty correspondence the reader becomes involved in the daily activities of those dedicated professionals who cared for the wounded in the less than ideal environments of war-torn North Africa and Italy. Entire hospital staffs were organized stateside and transported to areas close to the battlefields. Hospitals were often crude tent structures or were set up in abandoned buildings. Leaking tents, dirt floors, inadequate heating, and outside toilets added elements of adventure as well as frustration. Field hospitals and clearing stations were closer to the action and even more primitive. For history buffs or those who lived during World
792-1 One Year Clinical Follow-up of the Benestent Trial
Authors: C. Macaya, P. Serruys, H. Suryapranata, G. Mast, S. Klugmann, P. Urban, P. den Heijer, J. Piek, R. Simon, M. Morice, P. Crean, J. Bonnier, W. Wijns, N. Danchin, C. Bourdonnec
Journal: Journal of the American College of Cardiology (1995)
Risk of Primary and Recurrent Acute Myocardial Infarction From Lipoprotein(a) in Men and Women11This study was supported by grants from the National Heart Foundation of Australia, National Health and Medical Research Council of Australia, Newcastle.
Authors: SCOTT KINLAY, ANNETTE J DOBSON, RICHARD F HELLER, PATRICK McELDUFF, HILARY ALEXANDER, JOHN DICKESON
Journal: Journal of the American College of Cardiology (1996)
Polyphenon E<sup>®</sup> : a new treatment for external anogenital warts
Authors: S. Tatti, E. Stockfleth, K.R. Beutner, H. Tawfik, U. Elsasser, P. Weyrauch, A. Mescheder
Journal: British Journal of Dermatology (2009)

Journal Article Polyphenon E®: a new treatment for external anogenital warts Get access S. Tatti, S. Tatti The Hospital Clinicas, Universidad de Buenos Aires, Av. Cordoba 2351, Buenos Aires 1120, Argentina Silvio Tatti. E‐mail: siltatti@fibertel.com.ar Search for other works by this author on: Oxford Academic Google Scholar E. Stockfleth, E. Stockfleth The Hospital Clinicas, Universidad de Buenos Aires, Av. Cordoba 2351, Buenos Aires 1120, Argentina Search for other works by this author on: Oxford Academic Google Scholar K.R. Beutner, K.R. Beutner The Hospital Clinicas, Universidad de Buenos Aires, Av. Cordoba 2351, Buenos Aires 1120, Argentina Search for other works by this author on: Oxford Academic Google Scholar H. Tawfik, H. Tawfik The Hospital Clinicas, Universidad de Buenos Aires, Av. Cordoba 2351, Buenos Aires 1120, Argentina Search for other works by this author on: Oxford Academic Google Scholar U. Elsasser, U. Elsasser The Hospital Clinicas, Universidad de Buenos Aires, Av. Cordoba 2351, Buenos Aires 1120, Argentina Search for other works by this author on: Oxford Academic Google Scholar P. Weyrauch, P. Weyrauch The Hospital Clinicas, Universidad de Buenos Aires, Av. Cordoba 2351, Buenos Aires 1120, Argentina Search for other works by this author on: Oxford Academic Google Scholar A. Mescheder A. Mescheder The Hospital Clinicas, Universidad de Buenos Aires, Av. Cordoba 2351, Buenos Aires 1120, Argentina Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 1, 1 January 2010, Pages 176–184, https://doi.org/10.1111/j.1365-2133.2009.09375.x Published: 01 January 2010
Prognosis of Childhood Epilepsy — Another Look
Authors: Bruce O. Berg
Journal: New England Journal of Medicine (1982)

Until the past decade, attempts to obtain clinical data on epilepsy were hampered by the lack of a uniform classification of the epilepsies and by variability in recording and interpreting the electroencephalogram. Misconceptions and superstitions still surround the disorder, and historical data are sometimes questionable, if not actually inaccurate. Long-term, carefully controlled clinical studies of epileptic patients have been needed.The reported prevalence of childhood epilepsy has varied from two to eight cases per thousand population.1 One prospective study of 18,500 children, members of a group health plan who were followed from birth to five years of age, indicated that . . .
1362 RISK OF OBSTRUCTIVE SLEEP APNEA SYNDROME AND ASSOCIATION WITH LIVER DAMAGE IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE WITHOUT SEVERE OBESITY
Authors: E.A. Pulixi, E. Tobaldini, A.L. Fracanzani, N. Montano, S. Fargion, L. Valenti
Journal: Journal of Hepatology (2013)
Abstract 4463: Targeting SN38 delivery to gastrointestinal cancer cells using a fucose-bound nanoparticle approach
Authors: Junji Kato, Rishu Takimoto, Takahiro Osuga, Michihiro Ono, Masahiro Hirakawa, Makoto Yoshida, Yasushi Sato, Fumito Tamura
Journal: Cancer Research (2014)

Abstract Background &amp; Aims: Prognosis of patients with metastatic colorectal cancer (CRC) has been improving by introduction of molecular targeting therapy combined with chemotherapeutic agents. However, metastatic CRC still needs new strategies to improve treatment efficacy and survival rate. Increased expression of fucosyltransferases (FUTs) is common in CRC cells. FUTs are key enzymes accelerating malignant transformation through the fucosylation of different sialylated precursors, suggesting a crucial requirement for fucose by metastatic CRC cells. With this in mind, we developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specifically to CRC cells. Methods: L-fucose-bound liposomes were produced by the modified cholate dialysis method as vehicles for delivery of Cy5.5, FAM and SN38. The production of CA19-9 was measured by enzyme-linked immunosorbent assay. The CRC cell lines were exposed to SN38 or L-fucose-bound liposomes carrying SN38, and cytotoxicity was monitored with BrdU assay. Introduction of Cy5.5 or FAM by L-fucose-bound liposomes was analyzed by flow cytometry or fluorescence microscopy. The effect of L-fucose-bound liposome carrying SN38 in vivo was analyzed by intravenous injection in mice engrafted with CRC cell lines. All statistical tests were two-sided. Results: L-fucose-bound liposomes containing Cy5.5 or SN38 were effectively delivered into CA19-9 expressing CRC cancer cells. Excess L-fucose decreased the efficiency of Cy5.5 introduction by L-fucose-bound liposomes, suggesting L-fucose-receptor dependency. Intravenously injected L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition as well as prolonging survival in mouse xenograft models. Conclusions: Fucose-bound liposomes carrying anti-cancer drugs should provide a new strategy for patients with colorectal cancer. Citation Format: Junji Kato, Rishu Takimoto, Takahiro Osuga, Michihiro Ono, Masahiro Hirakawa, Makoto Yoshida, Yasushi Sato, Fumito Tamura. Targeting SN38 delivery to gastrointestinal cancer cells using a fucose-bound nanoparticle approach. [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 4463. doi:10.1158/1538-7445.AM2014-4463
Dermatology in an Age of Fully Transparent Electronic Medical Records
Authors: Jason P. Lott, Michael W. Piepkorn, Joann G. Elmore
Journal: JAMA Dermatology (2015)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Dermatology journal