tbuckley/cabot-search huggingface dataset:
Abstract 2045: Identifying key molecular events at the onset of melanoma using a neural crest stem cell marker
Authors: Charles K. Kaufman, Christian Mosimann, Richard M. White, Dominic Matos, Leonard I. Zon
Journal: Cancer Research (2014)

Abstract An ongoing challenge in cancer biology is understanding the earliest, initiating events that switch a premalignant cell into a fully competent cancer cell. Driven by this challenge, we focused on the zebrafish gene crestin that marks the embryonic neural crest from the onset of somitogenesis through 72 hours post fertilization when it normally turns off. Surprisingly, our lab previously showed that crestin mRNA is reexpressed in melanoma tumors in adult zebrafish, reading out a neural crest progenitor state. We have developed a fluorescent reporter using the crestin promoter/enhancer that recapitulates the embryonic expression pattern of crestin, and when bred into our BRAFV600E/p53 mutant melanoma zebrafish model, marks grossly visible melanoma tumors. Remarkably, we found that crestin:EGFP becomes active when lesions are only a few cells in number, potentially in the first cell of the melanoma. Using a crestin:CreERt2 inducible recombinase together with a lox-dependent fluorescent lineage tracer line ubi:switch, multiple neural crest descendant lineages including melanocytes can be traced. Further by expressing the melanocyte lineage master transcription factor mitf under the control of the crestin promoter, we can rescue melanocyte formation in mitf null embryos, and in the Na/BRAFV600E/p53 melanoma-prone mutant background, some adult fish develop darkly pigmented patches and melanoma tumors. Finally, we isolated small patches of crestin:EGFP positive cells and show that these precursor lesions are enriched for expression of the neural crest progenitor transcription factor sox10. These data support a model in which BRAFV600E/p53 mutated melanocytes stochastically reactivate an early melanocyte or neural crest progenitor program as read out by crestin reactivation at the initiation of melanoma formation. Using our novel reporter, we are able to analyze in vivo the earliest steps of cancer formation as well as the neural crest lineage program. Citation Format: Charles K. Kaufman, Christian Mosimann, Richard M. White, Dominic Matos, Leonard I. Zon. Identifying key molecular events at the onset of melanoma using a neural crest stem cell marker. [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 2045. doi:10.1158/1538-7445.AM2014-2045
AN OXYGEN MASK METERED FOR POSITIVE PRESSURE
Authors: Alvan L. Barach, Norman Molomut
Journal: Annals of Internal Medicine (1942)

Article1 November 1942AN OXYGEN MASK METERED FOR POSITIVE PRESSUREALVAN L. BARACH, M.D., F.A.C.P., NORMAN MOLOMUT, PH.D.ALVAN L. BARACH, M.D., F.A.C.P.Search for more papers by this author, NORMAN MOLOMUT, PH.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-17-5-820 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn the preceding paper1 the clinical advantage of breathing oxygen or oxygen-helium mixtures under positive pressure was described. When the head of the patient is placed within a hood that is made leaktight at the neck by a soft sponge rubber collar, positive pressure may be applied to the inner surface of the lung during inspiration and expiration.2 Since the technical management of a hood requires more careful supervision than is ordinarily available, we have added to a mask previously described3 a mechanism which provides positive pressure during the expiratory cycle.This consists of a series of apertures which are...Bibliography1. BARACH AL: Physiologically directed therapy in pneumonia, ANN. INT. MED., 1942, xvii, 812-819. Google Scholar2. ECKMANBARACH MAL: Technique of inhalational therapy, Modern Hosp., 1939, lii, 78. Google Scholar3a. BARACHECKMAN ALM: A mask apparatus which provides high oxygen concentrations with accurate control of the percentage of oxygen in the inspired air and without accumulation of carbon dioxide, Jr. Aviation Med., 1941, xii, 39-52. b. BARACH, A. L., and ECKMAN, M.: A physiologically controlled oxygen mask apparatus, Anesthesiology, 1941, ii, 421-426. Google Scholar4. BARACH AL: The therapeutic use of helium, Jr. Am. Med. Assoc., 1936, cvii, 1273. CrossrefGoogle Scholar5. BARACHSWENSON ALP: Effect of breathing gases under positive pressure on lumens of small and medium-sized bronchi, Arch. Int. Med., 1939, lxiii, 946. CrossrefGoogle Scholar6. BARACHMARTINECKMAN ALJM: Positive pressure respiration and its application to the treatment of acute pulmonary edema, ANN. INT. MED., 1938, xii, 754. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, N. Y.*Received for publication April 15, 1942.From the Department of Medicine, College of Physicians and Surgeons, Columbia University, and the Presbyterian Hospital, New York. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byBurns: A historical reflection on resuscitationTherapiePULMONARY EMPHYSEMA TREATED BY INTERMITTENT POSITIVE PRESSURE BREATHINGTherapieFacts and Fancies in the Management of the Seriously Ill Patient with Bronchial AsthmaPositive pressure respiration in the treatment of acute pulmonary edemaRepeated bronchial relaxation in the treatment of intractable asthma 1 November 1942Volume 17, Issue 5Page: 820-822KeywordsBreathingHospital medicineLungsOxygenSurgeons Issue Published: 1 November 1942 PDF downloadLoading ...
Relationship of Tumor Immunogenicity to Concentration of the Oncogen2
Authors: Richmond T. Prehn
Journal: JNCI Journal of the National Cancer Institute (1975)

Tumors were induced sc in (BALB/c x DBA/2)F1 female mice by various concentrations of 3-methylcholanthrene (MCA) in paraffin pellets. There was an inverse relationship between MCA concentration and tumor latency (interval between MCA implantation and detection of gross tumor). The tumors were transplanted into syngeneic recipients, and material from this first transplant generation was used to immunize a series of syngeneic mice; any resulting growth was excised. Nonimmunized mice were controls. Immunized and control mice were irradiated and given an sc inoculation of a near-threshold number of tumor cells. Tumor growth from that inoculation was measured weekly in both groups and the antigenicity ratio (mean tumor size in controls/mean tumor size in immunized mice) was calculated. In a series of tumors with similar latencies, the only ones with high antigenicity ratios were those resulting from the high MCA concentration. The results suggested that tumors induced by low levels of oncogen may be good models of spontaneous neoplasia, strengthened the hypothesis that "spontaneous' tumors may actually result from low levels of oncogen, and indicated that neoplastic transformation and the development of immunogenicity are, at least in chemically induced tumors, independent changes that may be produced in the same cell when the concentration of oncogen is sufficient.
Brief Report: The Value of a Patient Global Assessment of Disease Activity in Granulomatosis With Polyangiitis (Wegener's)
Authors: Gunnar Tomasson, John C. Davis, Gary S. Hoffman, W. Joseph McCune, Ulrich Specks, Robert Spiera, E. William St.Clair, John H. Stone, Peter A. Merkel
Journal: Arthritis & Rheumatology (2013)

To 1) describe the distribution of patient global assessment (PtGA) scores of disease activity in patients with granulomatosis with polyangiitis (GPA; Wegener's), 2) explore the discordance between PtGA scores and physician global assessment (PhGA) scores of disease activity, and 3) explore whether PtGA scores during disease remission are associated with future disease relapse.Data from the Wegener's Granulomatosis Etanercept Trial (WGET) were used. PtGA and PhGA scores were assessed on 100-mm visual analog scales (VAS). Presence of active disease was determined using the Birmingham Vasculitis Activity Score for WG (BVAS/WG), and remission was defined as a BVAS/WG score of 0. Disease relapse was defined as a BVAS/WG score of >0 after remission had been achieved. Discordance between PtGA and PhGA scores was defined as a difference of ≥20 points between the two measures. Mixed linear models were used in longitudinal analysis of PtGA scores.Data were obtained from 180 patients in the WGET cohort, seen at a total of 1,719 study visits. The mean ± SD PtGA and PhGA disease activity scores (on 100-mm VAS) at baseline were 64.2 ± 27.4 and 55.5 ± 23.4, respectively. PtGA-PhGA discordance occurred in 53% of patients at baseline, and this was inversely associated with newly diagnosed disease (as opposed to relapsing disease) at baseline (odds ratio 0.37, 95% confidence interval [95% CI] 0.20-0.68) but not with age, sex, or presence of renal or pulmonary disease. Patients were in disease remission during 62% of the study visits. The mean PtGA score during visits immediately prior to relapse was 4.52 points higher (95% CI 0.66-8.4) than that at other remission visits (P = 0.03).PtGA-PhGA discordance is common in GPA. A rise in the PtGA disease activity score during times defined by physicians as periods of remission is associated with subsequent occurrence of disease relapse. These findings support the addition of PtGA as an outcome measure for GPA.
Mammary Cancer in Fostered CBA Mice and CBA Hybrids2
Authors: John J. Bittner
Journal: JNCI Journal of the National Cancer Institute (1960)

In the absence of the mammary-tumor agent (MTA), breeding females of the CBA stock, observed since 1951, have remained free of spontaneous mammary cancer. After CBA young had been nursed by females of the cancerous Z (C3H) stock, to obtain the MTA, CBA breeders of the fostered and succeeding 3 generations had an incidence of 99 percent, with an average cancer age of 252 days. Because gonadectomized mice of the CBA stock developed adrenal cortical lesions, CBA males were mated with females of the A strain, which have a low incidence of mammary cancer in nonbreeders. The F1 females, maintained as virgins, showed a high incidence. These observations demonstrate that mice of the inbred CBA stock are susceptible to spontaneous mammary cancer and, in addition, transmit the mammary-cancer-inducing inherited hormonal pattern associated with postcastrational adrenal alterations.
Abstract 218: Using Regional Cerebral Oxygen Saturation Measurements to Study When to Deliver Shocks During CPR: Can Optimal Timing Be Determined?
Authors: Hitoshi Kano, Tomoyo Saito, Toshihisa Matsui, Akio Endo, Masaki Nagama, Wataru Iwanaga, Kanako Takahashi, Hiroshi Makise
Journal: Circulation (2014)

According to the present guidelines of cardiopulmonary resuscitation, the cardiac arrest algorithm suggests shocks be delivered soon after recognizing ventricular fibrillations (VF). In our study, we investigated the possibility that optimal timing to deliver shocks may exist and may be predicted by regional cerebral oxygen saturation measurements.   Methods:  From the onset of contact with cardiac arrest patients, the tissue oxygenation index (TOI) was continuously monitored (NIRO-200NX, Hamamatsu Photonics). In 19 patients who were delivered shocks following VF, we investigated the following parameters with respect to whether or not the return of spontaneous circulation (ROSC) was achieved: TOI value just before shocks during interruptions in chest compressions, (pre-shock TOI); TOI value during shocks (in-shock TOI); and the amount of decrease in TOI during interruption in chest compressions (ΔTOI).   Results:  The total number of shocks delivered was 37. In all of the shocks, the pre-shock TOI, the in-shock TOI and ΔTOI were 41.4±9.1%, 38.1±8.7% and -3.5±2.6%, respectively. In 5 shocks that resulted in ROSC, the in-shock TOI was 51.6±4.2%, and for 32 shocks that did not result in ROSC, the in-shock TOI was 36.6±7.7%.   Conclusion:  Values of the in-shock TOI measurements followed by ROSC were significantly higher than those that did not result in ROSC, and this outcome suggests shocks with low in-shock TOI readings may not achieve ROSC. Considering that TOI decreases when chest compressions are interrupted in preparation for the administration of shocks, better results may be achieved if the algorithm is adjusted to deliver shocks after TOI has reached a higher value.
INTOXICATION RESULTING FROM THE ADMINISTRATION OF MASSIVE DOSES OF VITAMIN D, With Report of Five Cases
Authors: G W COVEY, H H WHITLOCK
Journal: Annals of Internal Medicine (1946)

Article1 September 1946INTOXICATION RESULTING FROM THE ADMINISTRATION OF MASSIVE DOSES OF VITAMIN D, With Report of Five CasesGEO. W. COVEY, M.D., F.A.C.P., H. H. WHITLOCK, M.D.GEO. W. COVEY, M.D., F.A.C.P.Search for more papers by this author, H. H. WHITLOCK, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-25-3-508 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe fact that massive doses of vitamin D may produce toxic symptoms and even death in man has been recognized for many years. It is only in the past few years, however, that the administration of this substance in massive doses has become popular with physicians and that the misinformation relative to its merits in the treatment of arthritis publicized by a certain widely read "digest" of current literature has induced some people to use it in self-medication. In the past year we have recognized the syndrome of vitamin D intoxication in five patients whose records are briefly reported later...Bibliography1. RAPPAPORTREED BZCD: Viosterol of high potency in seasonal hay fever and related conditions, Jr. Am. Med. Assoc., 1933, ci, 105. CrossrefGoogle Scholar2. WYATTHICKSTHOMPSON BLRAEE: Massive doses of vitamin D in the treatment of proliferative arthritis, Ann. Int. Med., 1934, x, 534. Google Scholar3. REED CI: Symptoms of viosterol overdosage in human subjects, Jr. Am. Med. Assoc., 1934, cii, 1745. CrossrefGoogle Scholar4. VRTIAKLANG EGRS: Observations on the treatment of chronic arthritis with vitamin D, Jr. Am. Med. Assoc., 1936, cvi, 1162. CrossrefGoogle Scholar5. STECKDEUTSCHREEDSTRUCK IEHCIHC: Further studies on intoxication with vitamin D, Ann. Int. Med., 1937, x, 951. Google Scholar6. SLOCUMB CH: Vitamin D in the treatment of infectious arthritis, Ann. Int. Med., 1942, xvi, 241. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Lincoln, Nebraska*Received for publication February 5, 1946. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAcute Hypercalcemia Simulating Basilar-Artery InsufficiencyThe diagnostic spectrum of hypercalcemiaVITAMIN D INTOXICATION: REPORT OF TWO CASES TREATED WITH CORTISONE*JOHN V. VERNER JR., M.D., FRANK L. ENGEL, M.D., HARRY T. MCPHERSON, M.D.Disturbed Water-reabsorption by the Renal Tubules in two Patients with HypercalcaemiaVitamine und VitaminkrankheitenVitamin Supplementation in Health and DiseaseTreatment of endonasal and cutaneous lupus vulgaris with calciferol. with report of a successful cas 1 September 1946Volume 25, Issue 3Page: 508-515KeywordsArthritisIntoxicationVitamin D ePublished: 1 December 2008 Issue Published: 1 September 1946 PDF downloadLoading ...
CT Scanning for Minor Head Injury
Authors: Ian G Stiell, Catherine M Clement, Brian H Rowe, Robert Brison, George A Wells
Journal: JAMA (2006)

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 Journals 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
Abstract 10390: Prasugrel Treatment is More Effective in Reducing Platelet Reactivity in PCI Patients with Low Clopidogrel Response Compared to Dose Increase of Clopidogrel
Authors: Fabian Schmidtler, Evelyn Hitzke, Alexander Leber, Ellen Hoffmann, Dietmar Antoni
Journal: Circulation (2011)

A dual anti-platelet therapy is a routine procedure after PCI. A low response to thienopyridine treatment (LR) as determined by platelet function testing has been shown to be associated with a significantly increased risk for stent thrombosis and other ischemic events. In order to intensify the anti-platelet regimen patients can either be reloaded with clopidogrel with the subsequent increase of its daily dose to 150 mg/d or the treatment can be switched to prasugrel. Few studies are available so far which compare the efficacy of these treatments in patients with a LR to clopidogrel.   Methods:  Platelet function testing using multiple electrode aggregometry (Multiplate analyzer) was performed in 1028 patients undergoing PCI. Patients with low response to initial clopidogrel loading dose (600mg) and treatment (75mg) were either reloaded with 600 mg clopidogrel and then treated with daily 150mg clopidogrel (Group I, n=64) or were immediately switched to prasugrel loading dose (60mg) and standard daily therapy (10mg) (Group II, n=40). We retrospectively analysed the platelet function in both groups. Aggregation was tested one the first day after PCI in hirudin blood after stimulation of platelets with 6.4 µM ADP and expressed in Units (U). Prospectively a cut-off point > 42U was defined as LR,    Results:  In group I aggregation was 56±18 U (mean ± sd) before vs 39±19 U after reloading and therapy modification. 22 patients (34%) still showed a LR, while only 4 (6%) fulfilled the criteria of a HR to clopidogrel. In group II aggregation was 64±18 U before vs 29±17 U after switching to prasugrel. 6 patients showed a LR under prasugrel treatment (15%). 13 patients showed a HR to prasugrel treatment (32%).   Conclusions:  Prasugrel is significantly more effective in achieving sufficient platelet inhibition in low responders to the standard clopidogrel-dose compared to a dose increase of clopidogrel dose (reduction of the average aggregation by 54% vs. 31% for clopidogrel). The effect is achieved at the cost of an increased higher response rate which has been shown to be associated with more major bleeding.
Minimising the impact of visual impairment
Authors: T. H Margrain
Journal: BMJ (1999)

Visual impairment is responsible for much individual suffering and economic hardship. Magnifying devices and other types of low vision aid can significantly reduce the degree of handicap associated with impaired vision. Two thirds of the people who would benefit from a low vision aid (about 600 000 people in the United Kingdom), however, do not possess one.1 What are the reasons for this disturbing situation?

Currently about 316 000 people are registered as blind or partially sighted. However, the registers underestimate the number of people with low vision by a factor of three,2 so almost 1 000 000 people in the United Kingdom have untreatable low vision. Community based surveys support this estimate and have shown that around 20% of those aged 75 and over …
Treatment of Chronic Myelogenous Leukemia by Blocking Cytokine Alterations Found in Normal Stem and Progenitor Cells
Authors: Robert S. Welner, Giovanni Amabile, Deepak Bararia, Akos Czibere, Henry Yang, Hong Zhang, Lorena Lobo De Figueiredo Pontes, Min Ye, Elena Levantini, Annalisa Di Ruscio, Giovanni Martinelli, Daniel G. Tenen
Journal: Cancer Cell (2015)
Abstract A34: MC1R signaling reduces UV mutagenesis by ATR-mediated recruitment of XPA to photolesions
Authors: Stuart Gordon Jarrett, Erin M. Wolf Horrell, Perry A. Christian, Jillian C. Vanover, Mary C. Boulanger, Yue Zou, John August D'Orazio
Journal: Cancer Research (2015)

Abstract The melanocortin 1 receptor (MC1R), which signals through cAMP, is a melanocytic Gs-coupled transmembrane receptor activated by binding to its high-affinity ligand, α-melanocyte stimulating hormone (MSH). Besides influencing pigment phenotype and mediating adaptive tanning, MC1R signaling is intricately linked with genome maintenance and DNA repair. Individuals harboring loss-of-function MC1R polymorphisms are UV sensitive and melanoma-prone. We have determined that MC1R-mediated cAMP signaling promotes nucleotide excision repair (NER) in a cAMP-dependent protein kinase A (PKA)-dependent manner. PKA directly phosphorylates ataxia telangiectasia and Rad3-related protein (ATR) at Ser435 which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA) to sites of nuclear UV photodamage, accelerating clearance of UV-induced photolesions and reducing UV mutagenesis. Loss of Ser435 within ATR prevents PKA-mediated ATR phosphorylation, disrupts ATR-XPA binding, delays recruitment of XPA to UV-damaged DNA and elevates UV-induced mutagenesis. PKA-mediated ATR phosphorylation on Ser435 appears to induce a DNA repair-specific function of ATR independent of Chk1 phosphorylation and cell cycle arrest. Importantly, MC1R signaling defects and sub-optimal DNA repair are overcome by forskolin-mediated cAMP induction in melanocytes and in whole skin. Our findings mechanistically link cAMP-PKA signaling to NER and illustrate the potential benefits of cAMP pharmacological rescue to reduce UV mutagenesis in MC1R-defective, melanoma-susceptible individuals. Citation Format: Stuart Gordon Jarrett, Erin M. Wolf Horrell, Perry A. Christian, Jillian C. Vanover, Mary C. Boulanger, Yue Zou, John August D'Orazio. MC1R signaling reduces UV mutagenesis by ATR-mediated recruitment of XPA to photolesions. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A34.