tbuckley/cabot-search huggingface dataset:
Consortium 'Gangs Up' on Prostate Cancer
Authors: Phil Gunby
Journal: JAMA (1996)

CaP CURE'S LATEST APPROACH to finding a cure for prostate cancer is a consortium.  CaP CURE is the Association for Cure of Cancer of the Prostate ( JAMA . 1996; 275:350).  It was founded 3 years ago by the controversial investment banker Michael Milken, who usually is identified with so-called junk bonds and with playing a key role in reshaping capital markets. He took this step shortly after learning at age 46 of his own prostate cancer, radiation and hormone treatment outcome for which is being monitored closely as he enters his 50s.  So far, Milken has raised approximately $25 million in addition to contributions from his personal fortune to vitalize prostate cancer research by investigators who are exploring a variety of therapeutic, genetic, molecular, prophylactic, and diagnostic approaches with a new urgency. Typical of Milken's innovative, feet-to-the-fire emphasis is the unique new (10 months old) genetics consortium whose members made their
A novel selective small-molecule PI3K inhibitor is effective against human multiple myeloma in vitro and in vivo
Authors: J Glauer, N Pletz, M Schön, P Schneider, N Liu, K Ziegelbauer, S Emmert, G G Wulf, M P Schön
Journal: Blood Cancer Journal (2013)

Developing effective therapies against multiple myeloma (MM) is an unresolved challenge. Phosphatidylinositol-3-kinase (PI3K) activation may be associated with tumor progression and drug resistance, and inhibiting PI3K can induce apoptosis in MM cells. Thus, targeting of PI3K is predicted to increase the susceptibility of MM to anticancer therapy. The lead compound of a novel class of PI3K inhibitors, BAY80-6946 (IC50=0.5 nM against PI3K-α), was highly efficacious in four different MM cell lines, where it induced significant antitumoral effects in a dose-dependent manner. The compound inhibited cell cycle progression and increased apoptosis (P<0.001 compared with controls). Moreover, it abrogated the stimulation conferred by insulin-like growth-factor-1, a mechanism relevant for MM progression. These cellular effects were paralleled by decreased Akt phosphorylation, the main downstream target of PI3K. Likewise, profound antitumoral activity was observed ex vivo, as BAY80-6946 significantly inhibited proliferation of freshly isolated myeloma cells from three patients (P<0.001 compared with vehicle). In addition, BAY80-6946 showed convincing in vivo activity against the human AMO-1 and MOLP-8 myeloma cell lines in a preclinical murine xenograft model, where treatment with 6 mg/kg every other day for 2 weeks reduced the cell numbers by 87.0% and 69.3%, respectively (P<0.001 compared with vehicle), without overt toxicity in treated animals.
Intestinal mucosa in the Zollinger-Ellison syndrome
Authors: J. A. Parrish, D. C. Rawlins
Journal: Gut (1965)

EDITORIAL SYNOPSIS The gross hypersecretion of acid in the Zollinger-Ellison syndrome is shown to cause oedema, haemorrhages, and increased goblet cell formation in the duodenum in addition to the atypically sited duodenal ulcers.
Podoplanin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) localisation in primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC)
Authors: Aftab Ala, Richard Standish, Korsa Khan, Kenneth Hillan, Amar Dhillon, Humphrey Hodgson
Journal: Journal of Hepatology (2002)
Long-Term Outcomes of the Symmetry Vein Graft Anastomosis Device
Authors: Radha G. Kachhy, David F. Kong, Emily Honeycutt, Linda K. Shaw, R. Duane Davis
Journal: Circulation (2006)

The Symmetry Bypass Connector (St. Jude Medical) was developed to rapidly anastomose saphenous vein grafts to the aorta during coronary bypass surgery (CABG) without cross-clamping. Previous uncontrolled studies of this device observed vein graft closures at six months, possibly attributable to neointimal hyperplasia.To assess the long-term clinical outcomes of the Symmetry device, we performed a retrospective matched case-control analysis of patients who underwent CABG at Duke Medical Center between January 1, 2002 and December 31, 2003. In 121 patients, at least one proximal anastomosis used a Symmetry device. Traditional suture methods were used in 178 control patients, matched by age group, gender, use of cardiopulmonary bypass, and Hannan perioperative risk score. One-year outcomes were compared using the log-rank test and Cox proportional hazards regression models. Major adverse events were more frequent among cases compared with controls. By unadjusted Kaplan-Meier analysis for the composite end point of death, nonfatal myocardial infarction, repeat cardiac catheterization, or repeat CABG, there was a trend towards increased events in the Symmetry device group (P=0.053). No significant differences were detected for stroke, all cause mortality, or the combined end point of death or nonfatal myocardial infarction.Use of the Symmetry Bypass Connector was associated with increased risk for major adverse events at 1 year, suggestive of early graft closure. The potential reductions in operative stroke risk (from the elimination of aortic cross-clamping) must be weighed against the potential risk for later adverse events. These findings encourage close follow-up of patients who received this device.
THE ALUMINUM CENTENARY
Authors: E. E. Free
Journal: JAMA (1927)

<h3>To the Editor:</h3> —InThe Journal, March 19, page 928, I noted a little item referring to the centenary of aluminum and quoting Wöhler as the discoverer of this metal. Only a few weeks ago I was talking with Mr. Junius D. Edwards of the Aluminum Company of America about this very matter. Mr. Edwards convinced me, in the light of information recently dug up, that the real discovery of metallic aluminum was not made by Wöhler, but by Oersted.
Migratory traumatic cardiovascular foreign bodies.
Authors: R Moncada, T Matuga, E Unger, R Freeark, A Pizarro
Journal: Circulation (1978)

Six cases of cardiovascular foreign bodies secondary to trauma are presented. The various modes of entry and travel within the vascular are reviewed. Routine radiographic examination and angiography are shown to be the most useful techniques in defining the location and subsequent course of the foreign body in the vascular system.
THE MECHANISM OF AERIAL DISINFECTION BY GLYCOLS AND OTHER CHEMICAL AGENTS
Authors: Theodore T. Puck
Journal: The Journal of Experimental Medicine (1947)

Theoretical analysis of the mechanism of action of chemical aerial disinfectants reveals that the rapid killing action which is obtained cannot be accounted for by a collision process between germicidal aerosol particles and the air-borne bacteria. However, a mechanism involving condensation of germicide molecules in the vapor state on to the bacteria-containing droplets results in a theoretical velocity of the correct order of magnitude. Experimental tests of this theory show that pure germicide vapors free of aerosol droplets are almost instantly lethal to air-borne bacteria. Conversely, pure germicidal aerosols in the absence of vapor, had no effect on air-borne bacteria within 20 minutes or more. Therefore, it may be concluded on both theoretical and experimental grounds that rapid air sterilization requires the existence of the germicide in the vapor state.
Bone marrow-derived cells do not repair endothelium in a mouse model of chronic endothelial cell dysfunction
Authors: Tashera E. Perry, Minjung Song, Daryl J. Despres, Soo Mi Kim, Hong San, Zu-Xi Yu, Nalini Raghavachari, Jurgen Schnermann, Richard O. Cannon, Donald Orlic
Journal: Cardiovascular Research (2009)

Bone marrow (BM)-derived endothelial progenitor cells (EPCs) in the circulation replace damaged vascular endothelium. We assessed the hypothesis that a BM transplant from healthy animals would restore normal arterial endothelium and prevent hypertension in young endothelial nitric oxide synthase-deficient (eNOS−/−) mice. Radiation or busulfan-induced BM ablation in eNOS−/− mice on day 6, day 14, or day 28 was followed by a BM transplant consisting of enhanced green fluorescent protein positive (EGFP+) cells from C57BL/6J mice. Peripheral blood cell chimerism was always greater than 85% at 4 months after BM transplant. Molecular assays of heart, kidney, and liver revealed low-level chimerism in all treatment groups, consistent with residual circulating EGFP+ blood cells. When aorta, coronary, renal, hepatic, and splenic arteries in BM-transplanted eNOS−/− mice were examined by confocal microscopy, there were no EGFP- or eNOS-positive endothelial cells detected in these vessels in any of the treatment groups. Likewise, telemetry did not detect any reduction in blood pressure. Thus, no differences were observed in our measurements using several different treatment protocols. We found no evidence for BM-derived EPC renewal of endothelium in this eNOS-deficient mouse model of a chronic vascular disease or in wild-type mice during postnatal growth. Hence, renewal of chronic dysfunctional endothelium and endothelial homeostasis may be dependent on resident vascular progenitor cells.
Prolongation of activated clotting time (ACT) with tirofiban versus abciximab and its association to outcome: results from TARGET
Authors: David J. Moliterno, Richard A. Lange, Christian Hamm, Bernhard Meier, Peter M. DiBattiste, Nasser Lakkis, Jia Gang, Derek P. Chew, David M. Cohen, Gregg W. Stone, Laura Demopoulos, Eric J. Topol
Journal: Journal of the American College of Cardiology (2002)
Abstract LB-243: Discovery of single amino acid changes that confer constitutive activation of mTOR in human cancer
Authors: Fuyuhiko Tamanoi
Journal: Cancer Research (2010)

Abstract Mammalian target of rapamycin (mTOR), a serine/threonine kinase that belongs to the PI3K related kinase family, plays critical roles in a variety of cellular processes including protein synthesis, growth, cell cycle and autophagy in response to growth factor, nutrient and energy conditions. Overactivation of the mTOR signaling is observed in a number of human cancer. Inhibitors of mTOR such as rapamycin and its derivatives are being evaluated in clinical trials. Despite these developments that point to the significance of mTOR in human cancer, no mutations in mTOR have so far been identified in human cancer. Here we report novel mTOR mutations identified in human cancer by mining human cancer genome database. Of 889 cancer samples mined, we identified 14 amino acid changes in mTOR. Characterization of the mTOR signaling after expressing some of these mutants led to the identification of two single amino acid changes (S2215Y and R2505P) that confer constitutive activation of mTOR as detected by the phosphorylation of S6K, 4E-BP1 and S6 under nutrient starvation conditions. The mutation directly affects mTOR complex 1 (mTORC1), as the complex isolated from cells expressing the mutant mTOR after nutrient starvation still retained the activity to phosphorylate 4E-BP1 in vitro. On the other hand, we did not observe significant effects on the activity of mTORC2. The cells expressing the mTOR mutant exhibited resistance to cell size decrease by amino acid starvation and showed increased percentage of S-phase cells. The cells expressing the activated mutant were resistance to 1-butanol treatment and partially resistant to hydrogen peroxide treatment. However, they were sensitive to rapamycin. The mutations are located within the kinase domain at positions that correspond to regions where oncogenic mutations of PI3 kinase were identified. It is interesting to point out that the mTOR S2215Y mutation was identified in large intestine adenocarcinoma together with K-rasG13D mutation, while the mTOR R2505P mutation was identified in renal cell carcinoma together with CDC25A F218I mutation, raising the possibility that the mTOR mutations may cooperate with mutations in other signaling proteins. Since “we are moving into an era in which it will be possible to obtain the complete DNA sequence of large numbers of cancer genomes” (Stratton et al., Nature 458, 719), our study points to the idea that mTOR activating mutations can be identified in a wide range of human cancer yielding valuable information on the significance of mTOR in human cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-243.
Lost without translation?
Authors: Geoff Watts
Journal: BMJ (2010)

Purpose: While the recommended analysis method for magnetic resonance spectroscopy data is linear combination model (LCM) fitting, the supervised deep learning (DL) approach for quantification of MR spectroscopy (MRS) data recently showed encouraging results; however, supervised learning requires ground truth fitted spectra, which is not practical. This work investigates the feasibility and efficiency of the LCM-based self-supervised DL method for the analysis of MRS data. Method: We present a novel DL-based method for the quantification of relative metabolite concentrations, using quantum-mechanics simulated metabolite responses and neural networks. We trained, validated, and evaluated the proposed networks with simulated and publicly accessible in-vivo human brain MRS data and compared the performance with traditional methods. A novel adaptive macromolecule fitting algorithm is included. We investigated the performance of the proposed methods in a Monte Carlo (MC) study. Result: The validation using low-SNR simulated data demonstrated that the proposed methods could perform quantification comparably to other methods. The applicability of the proposed method for the quantification of in-vivo MRS data was demonstrated. Our proposed networks have the potential to reduce computation time significantly. Conclusion: The proposed model-constrained deep neural networks trained in a self-supervised manner with complex data can offer fast and efficient quantification of MRS data.
Carriage driving for disabled people.
Authors: J R Brown
Journal: BMJ (1990)

Summary   This paper describes the origin of Driving for the Disabled groups which have been formed since the early 1970s. Carriage driving for disabled people was relatively unknown before that time but now, thanks to help from the Riding for the Disabled Association, the British Driving Society, and numerous volunteers, people with varying degrees and types of disability can enjoy the activity and compete alongside able-bodied drivers. There are many beneficial effects both physical and psychological, and the author thoroughly recommends carriage driving as a liberating experience for anyone with a love of horses and outdoor activity.
Renal biopsy findings in long-term cyclosporin treatment of psoriasis
Authors: H. ZACHARIAE, K. KRAGBALLE, H.E. HANSEN, N. MARCUSSEN, S. OLSEN
Journal: British Journal of Dermatology (1997)

Renal biopsies were performed in 30 psoriatics during long-term low-dose cyclosporin (CsA) therapy (range 2.5-6 mg/kg per day) of from 6 months to 8 years. The study included pretreatment biopsies in 25 of the patients. After 2 years all biopsies shared features consistent with CsA nephropathy despite completely normal pretreatment morphology in 17 of the 25 patients. The severity of the findings which consisted of arteriolar hyalinosis, focal interstitial fibrosis and sclerotic glomeruli increased with length of therapy. Mild renal lesions were seen during the first 2 years. After 4 years all but one had arteriolar hyalinosis, with interstitial fibrosis pronounced in five and moderate in six of 11 patients. At the same time glomerular sclerosis had become significant. A decrease in glomerular filtration rate (GFR) correlated with severity of structural lesions. The data from our study together with experiences from cardiac-transplanted patients treated with CsA indicate that patients with psoriasis after 2 years therapy with CsA should be rotated to other treatments or be followed carefully by GFR and sequential renal biopsies.
Spontaneous pseudomembranous colitis.
Authors: J M Howard, S N Sullivan, M Troster
Journal: BMJ (1980)

insulin, but if satisfactory control cannot be achieved in our patient, with her present diet and large doses of oral hypoglycaemic agents, the only course would be to attempt desensitisation to insulin.We thank Mr C A Barnes for technical help with immunological procedures, Dr A Kurtz, Middlesex Hospital Medical School, for measuring IgG insulin antibodies, and Dr Lovett (Burroughs Wellcome) for the gift of bovine monocomponent insulin.
An Overview of Reform Initiatives in Medical Education
Authors: C Enarson, F D Burg
Journal: JAMA (1992)

INTEREST in alternative educational, organizational, and financing strategies for the education of the next generation of physicians is growing as medical care costs escalate and access to basic health care declines. To assess the impact of major initiatives for improving undergraduate medical education, we reviewed 15 major studies conducted between 1906 and 1992 (Table).<sup>1-15</sup>Eleven of these studies originated with councils or commissions whose appointed members reviewed the ideas and opinions of leaders in medicine about medical education<sup>1,10,14</sup>; four were detailed field studies,<sup>11-13,15,16</sup>consisting of on-site observations of the structure and function of specific medical education programs. Of the 15 initiatives, 13 reported specific recommendations,<sup>1-13</sup>which can be grouped in three categories: the method of medical school instruction, ie, the curricula content and process of instruction; the internal structure of medical schools; and the relationship between medical schools and external organizations and agencies. The recommendations are
EPINEPHRIN AND SUPRARENAL GLAND IN INTERNAL MEDICINE
Authors: HENRY A. CHRISTIAN
Journal: JAMA (1924)

In considering the therapeutic action of glands of internal secretion, one must distinguish between the action of gland preparations in a replacement sense, in which the preparation supplies a deficiency due to a disturbance of the function of the same gland, and the pharmacologic action of gland preparations on a person who has no evidence of disturbed function of the gland from which the preparation was obtained. An extreme example of the latter occurs in connection with the thyroid. Iodin may be obtained from the thyroid; this iodin would have the same therapeutic action as iodin in the same form from any other source, and no one would regard this as any more than the usual pharmacologic or therapeutic effect of the substance instead of thinking of it as in any way related to the internal secretion of the thyroid gland. In this way one must consider the therapeutic effect
Nerve Cells in Organotypic Cultures
Authors: Beat H. Gähwiler
Journal: JAMA (1981)

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
Global DNA Hypomethylation Is Associated with High Serum-Persistent Organic Pollutants in Greenlandic Inuit
Authors: Jennifer A. Rusiecki, Andrea Baccarelli, Valentina Bollati, Letizia Tarantini, Lee E. Moore, Eva C. Bonefeld-Jorgensen
Journal: Environmental Health Perspectives (2008)

Persistent organic pollutants (POPs) may influence epigenetic mechanisms; therefore, they could affect chromosomal stability and gene expression. DNA methylation, an epigenetic mechanism, has been associated with cancer initiation and progression. Greenlandic Inuit have some of the highest reported POP levels worldwide.Our aim in this study was to evaluate the relationship between plasma POPs concentrations and global DNA methylation (percent 5-methylcytosine) in DNA extracted from blood samples from 70 Greenlandic Inuit. Blood samples were collected under the Arctic Monitoring and Assessment Program and previously analyzed for a battery of POPs.We used pyrosequencing to estimate global DNA methylation via Alu and LINE-1 assays of bisulfite-treated DNA. We investigated correlations between plasma POP concentrations and global DNA methylation via correlation coefficients and linear regression analyses.We found inverse correlations between percents methylcytosine and many of the POP concentrations measured. Linear regressions, adjusting for age and cigarette smoking, showed statistically significant inverse linear relationships mainly for the Alu assay for p,p'-DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane; beta = -0.26), p,p'-DDE [1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene; beta = -0.38], beta-hexachlorocyclohexane (beta = -0.48), oxychlordane (beta = -0.32), alpha-chlordane (beta = -0.75), mirex (beta = -0.27), sum of polychlorinated biphenyls (beta = -0.56), and sum of all POPs (beta = -0.48). Linear regressions for the LINE-1 assay showed beta estimates of similar magnitudes to those using the Alu assay, however, none was statistically significant.This is the first study to investigate environmental exposure to POPs and DNA methylation levels in a human population. Global methylation levels were inversely associated with blood plasma levels for several POPs and merit further investigation.
A mixture of medication
Authors: M. Gutenstein
Journal: BMJ (2003)

A delightful couple came to the emergency department recently. Married for many years, they had become mutually dependent courtesy of atherosclerosis. Her diabetes and stroke and his angina and heart failure had slowed them up somewhat, but still they managed with a little help. Every morning and evening they would each tip seven or eight pills from white pill boxes into an eggcup and take them with a …