tbuckley/cabot-search huggingface dataset:
PTH-118 Adherence To Duodenal Biopsy Guidelines Increases The Detection Of Coeliac Disease: A Multicentre Uk Study
Authors: PD Mooney, M Finegan, F Khan, R Keld, G Naylor, DS Sanders
Journal: Gut (2014)

We have previously described the development of a lipopeptide-based vaccine, Theradigm-HBV, capable of inducing CTL responses in humans. This vaccine incorporates the HLA-A2.1-restricted CTL epitope hepatitis B core Ag 18-27, linked to the universal helper T lymphocyte (HTL) epitope tetanus toxoid (TT) 830-843. Herein, we report the results of a phase I trial designed to examine the effects of Theradigm-HBV dose and regimen on the magnitude and duration of the memory CTL response. A total of four injections of up to 5 mg/dose were found to be a safe and effective means of generating substantial memory CTL responses. Precursor frequency analysis demonstrated CTL responses of similar magnitude to those previously observed in patients who successfully cleared hepatitis B virus infection and to influenza-specific memory CTL responses induced by natural exposure to influenza virus. Theradigm-HBV induced CTL responses that persisted for more than 9 months after the last injection. HTL responses were associated with significant CTL responses, and sustained HTL activity was necessary for development of persistent memory CTL activity. These results represent the first demonstration of the importance of HTL activity for development of long-lived memory CTL responses in humans. In conclusion, our results show that lipopeptides safely induce specific CTL activity in humans of such magnitude and persistence as to be of potential therapeutic significance.
Abstract 14360: Gene Transfer of Sarco/Endoplasmic reticulum Ca2+-ATPase 2a Restores Pulmonary Artery Endothelial Catechol-O-Methyltransferase Activity to Decrease Norepinephrine Levels in Pulmonary Hypertension
Authors: Samantha Torquato, Jaume Aguero, Kiyotake Ishikawa, Lahouaria Hadri, Joseph Loscalzo, Bradley A Maron, Roger J Hajjar, Jane A Leopold
Journal: Circulation (2015)

Elevated levels of norepinephrine (NE) may occur in pulmonary hypertension (PH), in part, when activity of catechol- O -methyltransferase (COMT) is decreased. COMT is expressed by pulmonary artery endothelial cells (PAEC), degrades NE, and is negatively regulated by aldosterone (ALDO) and cytosolic Ca 2+ . Expression of the cardiac isoform of the sarco/endoplasmic Ca 2+ -ATPase (SERCA2a) modulates ALDO and cytosolic Ca 2+ and is downregulated in pulmonary arteries in PH. We hypothesized that gene transfer of SERCA2a to pulmonary arteries would prevent the decrease in COMT activity and lower NE levels. Accordingly, human PAEC were infected with an adenovirus encoding SERCA2a to increase expression 4.2-fold (p&lt;0.01) or control virus and exposed to ALDO (10 -7 mol/L), which decreases COMT activity by 59.2 ± 6.2% (p&lt;0.01). Compared to controls, SERCA2a overexpression in PAEC had no effect on COMT mRNA or protein levels but increased COMT activity by 148.8 ± 14.5% (p&lt;0.01) by decreasing cytosolic Ca 2+ levels by 38.2 ± 6.7% (p&lt;0.05). This resulted in a decrease in NE levels in the medium (229.4 ± 20.6 vs. 139.9 ± 14.8 vs. pg/mg protein, p&lt;0.01) and collagen I expression. To examine the in vivo relevance of SERCA2a gene transfer on COMT activity, the rat monocrotaline model of PH was treated with inhaled adeno-associated virus 1 carrying SERCA2a (AAV1.SERCA2a). There was no difference in COMT expression in AAVI.SERCA2a-treated or saline control PH-rats; however, lung COMT activity was increased 139.8 ± 8.2% (p&lt;0.01) while lung levels of NE (366.7 ± 38.6 vs. 504 ± 30.2 pg/ml/mg, p&lt;0.01), serum ALDO, and pulmonary artery collagen 1 were decreased by AAV1.SERCA2a. In the pig pulmonary vein banding model of PH, inhaled AAV1.SERCA2a gene therapy decreased mean pulmonary artery pressure (54 ± 20 vs. 29 ± 5 mmHg, p&lt;0.03); increased COMT activity by 121.1 ± 6.2% (p&lt;0.05); and decreased levels of ALDO by 43.3 ± 4.6% (p&lt;0.03), NE by 43.3 ± 4.6% (p&lt;0.03), and collagen I in remodeled vessels. Taken together, these data indicate that gene therapy with inhaled AAV1.SERCA2a increases COMT activity by decreasing intracellular Ca 2+ , thereby decreasing NE levels. This extends the actions of SERCA2a beyond pulmonary vascular remodeling in PH to modulating levels of circulating catecholamines.
ON THE INFLUENCE OF METEOROLOGICAL CONDITIONS ON THE DEVELOPMENT OF TRYPANOSOMA RHODESIENSE IN GLOSSINA MORSITANS
Authors: A. Kinghorn, W. Yorke
Journal: BMJ (1912)

Oin S1-eptemiber 9tlh hie slhowved mc soniie peculiar ;bodies' wlhich lbe hal found l)y this metlhod in syplhilitic clhancre scraping.s.In consequence, I lhave followecd this miethod, aI(i hiere describe the bodies I have seen whlile working witl the jellies imyself.I mialkc the jellies as follows:Agar, 1 gramn; sodium clhloride, 0.5 graiam; polyclirome rnetlylene blue, 4 c.Clll; distilled water, 100 c.crn.; boil, filter, Ruld( store iin test tubes.When required for use, the jelly is; rmielte(d aind a small quanitity is poured on to a slide to cover an area of about a s(iuare inlcli anid allowed to cool and set.The syplhilitic imaterial to be examined is obtained from-i lard chlancre; a drop of the scraping is mixed with an equal quantity of a 3 per cent.solution of sodiulmi citrate in water.anid placed on a cover-slip, which is inverted on to thel surface of the set jelly.Or a hard, " shotty " syphilitic gland is pulcetulred with a Bayly needle and the gland squceezed; after a miiinute the needle is withdrawni, and the nliaterial conitained in it is expelled into the citrate solution its before.On thle jelly the cells, leucocytes, epitlielial cells, lymuiliocytes, stain a aeneral blue; tlle bodies" stain red, and this serves to-distinguish them readily.I lhave examined 25 clhancres and 22 glands by thjis method, and lhave found thle bodies in every syphilitic case.They may be dlescribed as (1) extracellular, (2) intracellular.The former consist of two forms: (a) Oval bodies 2 to 10 miiicrons in diam-leter, containing a granular nucleus and one or two clhroiuatin dots (Fig. 1); (b) bodies varying in
General Surgery
Authors: Elsa R. Hirvela
Journal: JAMA (1994)

The happy cohabitation of surgery with basic science has experienced another productive year. Basic science research is not easily translated into clinical usefulness. The downsizing of federal funding and the increasing participation of the biomedical-industrial complex has affected surgical research. New diagnostic modalities in the panoperative setting have seen increasing application within the last year that affects the volume, type, and extent of future operations. The widespread application of screening mammography has led to an increase (up to sixfold) in the number of open breast biopsies performed for mammographic abnormalities. Most such radiologic findings correspond to benign processes, but the cost to prove benignancy is substantial. Stereotactic automated core breast biopsy is a method of precisely directed tissue sampling that can be performed with the patient under local anesthesia. Comparison of tissue diagnosis using this technique followed by open biopsy in a study of 98 lesions showed a high correlation.
MILLIONS FOR MEDICAL SCHOOL.
Journal: JAMA (1902)

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 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) 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
Odysseus
Authors: George N. Braman
Journal: Annals of Internal Medicine (2011)

Ad Libitum20 September 2011OdysseusGeorge N. Braman, MDGeorge N. Braman, MDFrom Bronx, NY 10471-1609.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-6-201109200-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Estuary or inlet of the sea,Where ocean surf meets fresh water, a blendOf salt and air, a flow, an urgency,A resistance overcome, journey's end.Sanctuary for seaworthy and soundOld weather-beaten ships, well past their prime—But staunch, not yet ready to go agroundTreading water, buttressed by tides and time;Meeting of ocean wave and inland stream,Commingling of waters, secret sharing—A haven for the rogue who dares to dream,The old salt still stubborn in his sailing—I am coming home (pausing in my quest)To drift casually ashore, and to rest. Author, Article, and Disclosure InformationAffiliations: From Bronx, NY 10471-1609.Dr. Braman passed away on 23 June 2010. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 September 2011Volume 155, Issue 6Page: 394KeywordsAir flowRiversSalts ePublished: 20 September 2011 Issue Published: 20 September 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
The emergence of Escherichia coli O157:H7 infection in the United States. The changing epidemiology of foodborne disease
Authors: K. L. MacDonald
Journal: JAMA (1993)

In this issue ofThe Journal, Besser et al present findings from an outbreak of<i>Escherichia coli</i>O157:H7 that occurred in southeastern Massachusetts in the fall of 1991.<sup>1</sup>Twenty-three cases of<i>E coli</i>O157:H7 infection were identified; four had a diagnosis of hemolytic uremic syndrome (HUS), which is a well-recognized complication of<i>E coli</i>O157:H7 infection. The outbreak was identified because the cases of HUS clustered in time at one hospital. A well-conducted case-control study implicated apple cider as the vehicle of transmission. While this is an unusual vehicle for a foodborne pathogen, the authors offer data from inoculation studies showing that<i>E coli</i>O157:H7 organisms can survive for many days in refrigerated cider. In addition, the authors cite two previously reported outbreaks of illness associated with drinking apple cider. Interestingly enough, one was an outbreak of HUS and was probably caused by<i>E coli</i>O157:H7 organisms. See also
Gender verification and the next Olympic games
Authors: B. Dingeon
Journal: JAMA (1993)

<h3>In Reply.</h3> —We are pleased to have the opportunity to respond to Dr Dingeon and to update the IAAF position on gender verification. First, Dingeon is incorrect in stating that we advocated a physical examination for all athletes at every competition. Instead, we recommended only examination in the home country, complemented by spot checks at competition sites. Furthermore, the IAAF never advocated a "gynecological test" (presumably, an internal pelvic examination). Since our February 1992 Commentary, the IAAF has updated its position. Gender verification has now been abandoned, as a result of a second IAAF Working Group (London, England, May 1992). None of the team physicians present at that meeting were aware of attempts by athletes to masquerade in their own country. The physicians found it incredible that men could, in the 1990s, masquerade as women, given the requirement for urine testing for doping. The urine sample obligatorily required to detect
RTOG 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM).
Authors: Mark R. Gilbert, James Dignam, Minhee Won, Deborah T. Blumenthal, Michael A. Vogelbaum, Kenneth D. Aldape, Howard Colman, Arnab Chakravarti, Robert Jeraj, Terri S. Armstrong, Jeffrey Scott Wefel, Paul D. Brown, Kurt A. Jaeckle, David Schiff, James Norman Atkins, David Brachman, Maria Werner-Wasik, Ritsuko Komaki, Erik P. Sulman, Minesh P. Mehta
Journal: Journal of Clinical Oncology (2013)

1 Background: Chemoradiation (CRT) with temozolomide (TMZ/RT→TMZ) is the standard of care for newly diagnosed GBM. This trial determined if the addition of Bev to standard CRT improves survival (OS) or progression-free survival (PFS) in newly diagnosed GBM. Methods: This phase III trial was conducted by the RTOG, NCCTG, and ECOG. Neurologically stable pts &gt; 18 yrs with KPS ≥ 60, and &gt; 1cm 3 tumor tissue block, were randomized to Arm 1: standard CRT + placebo or Arm 2: standard CRT plus Bev (10 mg/kg iv q 2wks). Experimental treatment began at wk 4 of radiation then thru 6-12 cycles of maintenance chemotherapy. Protocol specified co-primary endpoints were OS and PFS, with significance levels of .023 and .002, respectively. At progression, treatment was unblinded and pts allowed to crossover or continue Bev. Symptom, QOL and neurocognitive (NCF) testing was performed in the majority of pts. Secondary analyses evaluated impact of MGMT methylation (meth) and prognostic 9 gene signature status. Results: From 978 registered pts, 637 were randomized. Inadequate tissue (n=105) and blood on imaging (n=40) were key reasons for non-randomization. No difference was found between arms for OS (median 16.1 vs. 15.7 mo, p = 0.11). PFS was extended for Arm 2 (7.3 vs. 10.7 mo, p = 0.004). Pts with MGMT meth had superior OS (23.2 vs. 14.3 mo, p &lt; 0.001) and PFS (14.1 vs. 8.2 mo, p &lt; 0.001). Neither the 9 gene signature nor MGMT predicted selective benefit for Bev treatment, but best prognosis pts (MGMT meth, favorable 9-gene), had a worse survival trend with Bev (15.7 vs 25 mo p = 0.08). To date, 128 pts were unblinded on Arm 1 (salvage Bev in 86) and 87 pts on Arm 2 (continued Bev in 39). Increased grade ≥ 3 toxicity was seen with Bev, mostly neutropenia, hypertension, and DVT/PE. Conclusions: The addition of Bev for newly diagnosed GBM did not improve OS, did improve PFS but did not reach the significance criterion. MGMT and 9 gene profile did not identify selective benefit, but risk subset results suggested strongly against the upfront use of Bev in the best prognosis pts. Full interpretation of the PFS results incorporating symptom burden, QOL, and NCF is ongoing. Support: NCI U10 CA 21661, U10 CA37422, and Genentech. Clinical trial information: NCT00884741.
Proc Soc Exper Biology &amp;amp; Medicine, New York
Journal: JAMA (1965)

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 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) 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
DISSEMINATED HERPES SIMPLEX VIRUS INFECTION
Journal: JAMA (1968)

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 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) 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
More About: Modification of Clinical Presentation of Prostate Tumors by a Novel Genetic Variant in CYP3A4
Authors: T. R. Rebbeck
Journal: JNCI Journal of the National Cancer Institute (2000)

Prostate Tumors by a Novel Genetic Variant in CYP3A4CYP3A4 is a member of the cytochrome P450 supergene family that mediates the metabolism of numerous compounds involved in human carcinogenesis, including steroid hormones such as testosterone.Recently, a variant in the 5Ј regulatory region of CYP3A4 (CYP3A4-V) was reported to confer higher stage prostate tumors compared with homozygous wild-type CYP3A4 (CYP3A4-W) in both Caucasians and African-Americans (1,2).To date, these associations have not been supported by data that address the functional significance of this polymorphism.Westlind et al.(3) recently reported that CYP3A4-V had no effect on testosterone 6␤-hydroxylation (T6␤H).However, this inference was made without any formal statistical analysis.By using the raw data provided in that paper, genotype-specific mean values of T6␤H were computed.The mean T6␤H in CYP3A4-W homozygotes (n ‫ס‬ 36) was 1660.6 pmol/mg per minute, whereas the mean T6␤H in carriers of a CYP3A4-V allele (n ‫ס‬ 3) was 4850.0 pmol/mg per minute.This difference was highly statistically significant by analysis of variance with F 1,37 ‫ס‬ 13.85 (P ‫ס‬ .0007)and by Kruskal-Wallis analysis of variance by ranks with 2 1
Observations of Cancer Incidence Surveillance in Duluth, Minnesota
Authors: Eunice E. Sigurdson
Journal: Environmental Health Perspectives (1983)

In 1973, amphibole asbestos fibers were discovered in the municipal water supply of Duluth, Minnesota. The entire city population of approximately 100,000 was exposed from the late 1950s through 1976 at levels of 1-65 million fibers per liter of water. Because of previous epidemiologic studies that linked mesothelioma, lung and gastrointestinal cancers to occupational exposure to asbestos, surveillance of cancer incidence in residents of Duluth was initiated to determine the health effect from ingestion of asbestos. The methodology of the Third National Cancer Survey (TNCS) and SEER Program was used. Duluth 1969-1971 rates were compared with TNCS rates for the cities of Minneapolis and St. Paul during 1969-1971; Duluth rates during 1974-1976 are compared with Duluth 1969-1971; Duluth rates during 1979-1980 are compared with Duluth 1969-1971 and with Iowa SEER; and a table of the occurrence of malignant mesothelioma is presented. Statistically significant excesses are observed in several primary sites in Duluth residents. However, lung cancer in Duluth females is the only primary site considered also of biological significance. The mesothelioma incidence rate is no more than expected. This paper also describes the problems of long-term surveillance of exposed populations considered at risk of environment cancer, the need for improved study methodologies and the use of federal records for follow up of exposed individuals.
Bacteroidaceae bacteremia. Effect of age and focus of infection upon clinical course
Authors: A. F. Gelb
Journal: JAMA (1970)

In 35 cases of anaerobic gram-negative rod (Bacteroidaceae) bacteremia only one of the 23 patients under 40 years of age died. The 12 patients more than 40 years of age died in septicemic shock. Female genital tract infection secondary to incomplete septic abortion accounted for 18 cases. The gastrointestinal tract, decubitus ulcers, and the urinary tract were responsible for a total of 12 cases. The clinical course in patients with Bacteroidaceae bacteremia secondary to incomplete septic abortion was characteristically milder than in patients with bacteremia from other foci. Bacteroidaceae bacteremia has many similarities with bacteremia from aerobic gram-negative rod organisms except that jaundice, liver abscess, and pylephlebitis are more common in Bacteroidaceae bacteremia.
STEM-21. CONTEXT-SPECIFIC TUMOR SUPPRESSIVE FUNCTION OF THE CANONICAL Wnt PATHWAY IN PEDIATRIC MEDULLOBLASTOMA HIGHLIGHTS A THERAPEUTIC STRATEGY FOR TREATMENT-REFRACTORY SUBGROUPS
Authors: Branavan Manoranjan, Chitra Venugopal, Michelle Kameda-Smith, David Bakhshinyan, Minomi Subapanditha, Bradley Doble, Sheila Singh
Journal: Neuro-Oncology (2017)

Current molecular subgroups of childhood medulloblastoma (MB) recognize distinct disease entities of which activated Wnt signaling is associated with a distinct subgroup and the best overall outcome. In contrast, non-Wnt MBs are characterized by metastatic disease, increased rate of recurrence, and poor overall survivorship. Given the excellent clinical outcome in Wnt-driven MB, we aimed to convert treatment-resistant MB subgroups 3 and 4 into an ostensibly benign tumor. Activated Wnt signaling by way of Wnt agonists decreased in vitro self-renewal of primary MB cells. Comparative RNA-sequencing of control and transgenic lines containing a stabilized beta-catenin mutant demonstrated a reduction in self-renewal genes following beta-catenin overexpression, including Sox2 and Bmi1. In order to validate the therapy-sensitive nature of Wnt-activated cells, we developed stable human Group 3 and 4 patient-derived lines containing a 7XTOPFlash reporter to determine the presence of endogenous Wnt signaling. Rare subclonal Wnt-active cells demonstrated a reduced self-renewal and tumor-initiating capacity through in vivo limiting dilution assays when compared to bulk Wnt-inactive cells from Group 3 and 4 MBs. The therapeutic relevance of these findings were demonstrated with an in vivo survival advantage in mice with orthotopic injections of cells containing stabilized beta-catenin overexpression or endogenous Wnt-active cells. Resulting xenograft tumors were smaller in size, maintained a lower rate of proliferation, and reduction in MB self-renewal genes. To develop a rationale clinical therapeutic, we used a novel substrate-competitive peptide inhibitor for GSK. Treatment with our peptide inhibitor showed a significant reduction in tumor burden and metastatic disease with a corresponding increase in survival of patient-derived Group 3 and 4 tumors that were otherwise treatment-resistant. Our work establishes activated Wnt signaling as a novel treatment paradigm in childhood MB, identifies a rationale therapeutic approach for recurrent MB, and provides evidence for the context-specific tumor suppressive function of the canonical Wnt pathway.