tbuckley/cabot-search huggingface dataset:
[Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 Is a Highly Efficient Radiotherapeutic for Glucagon-Like Peptide-1 Receptor–Targeted Therapy for Insulinoma
Authors: Andreas Wicki, Damian Wild, Daniel Storch, Christian Seemayer, Martin Gotthardt, Martin Behe, Stefan Kneifel, Michael J. Mihatsch, Jean-Claude Reubi, Helmut R. Mäcke, Gerhard Christofori
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Although metabolic changes make diagnosis of insulinoma relatively easy, surgical removal is hampered by difficulties in locating it, and there is no efficient treatment for malignant insulinoma. We have previously shown that the high density of glucagon-like peptide-1 receptors (GLP-1R) in human insulinoma cells provides an attractive target for molecular imaging and internal radiotherapy. In this study, we investigated the therapeutic potential of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4, an 111In-labeled agonist of GLP-1, in a transgenic mouse model of human insulinoma. Experimental Design: [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 was assessed in the Rip1Tag2 mouse model of pancreatic β-cell carcinogenesis, which exhibits a GLP-1R expression comparable with human insulinoma. Mice were injected with 1.1, 5.6, or 28 MBq of the radiopeptide and sacrificed 7 days after injection. Tumor uptake and response, the mechanism of action of the radiopeptide, and therapy toxicity were investigated. Results: Tumor uptake was &amp;gt;200% injected activity per gram, with a dose deposition of 3 Gy/MBq at 40 pmol [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4. Other GLP-1R–positive organs showed ≥30 times lower dose deposition. A single injection of [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 resulted in a reduction of the tumor volume by up to 94% in a dose-dependent manner without significant acute organ toxicity. The therapeutic effect was due to increased tumor cell apoptosis and necrosis and decreased proliferation. Conclusions: The results suggest that [Lys40(Ahx-DTPA-111In)NH2]-Exendin-4 is a promising radiopeptide capable of selectively targeting insulinoma. Furthermore, Auger-emitting radiopharmaceuticals such as 111In are able to produce a marked therapeutic effect if a high tumor uptake is achieved.
3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Decrease Fas Ligand Expression and Cytotoxicity in Activated Human T Lymphocytes
Authors: Luis Miguel Blanco-Colio, Begoña Muñoz-García, Jose Luis Martín-Ventura, Corina Lorz, Cristina Díaz, Gonzalo Hernández, Jesús Egido
Journal: Circulation (2003)

HMG-CoA reductase inhibitors reduce cardiovascular mortality, although the mechanisms of action have not been completely elucidated. The presence of T cells and apoptotic cells in atherosclerotic plaques is well established, the reduction of cellular content being a marker of their vulnerability. One of the main mechanisms of cell death activation is the Fas-Fas ligand (FasL) system.We studied whether HMG-CoA reductase inhibitors can regulate FasL expression and cytotoxicity in human T cells (Jurkat cells). Activation of Jurkat cells with phorbol esters and ionomycin increased FasL expression, an effect prevented by atorvastatin or simvastatin. Mevalonate and geranylgeranylpyrophosphate but not farnesylpyrophosphate prevented the effect of atorvastatin, indicating that protein geranylation was involved in FasL expression. The C3 exotoxin, which selectively inactivates Rho proteins, also decreased FasL expression on T cells. Overexpression of constitutively active RhoA increased FasL expression in Jurkat cells, and dominant-negative RhoA decreased FasL expression in activated cells, indicating that RhoA is implicated in FasL expression. Atorvastatin also decreased cytotoxic activity of activated Jurkat cells on FasL-sensitive cells. Finally, atorvastatin treatment reduced FasL expression in peripheral blood mononuclear cells and human carotid atherosclerotic plaques.Atorvastatin regulates FasL expression in T cells, probably because of the inhibition of RhoA prenylation. These results provide novel information by which atorvastatin may regulate the cytotoxic activity of T cells and the number of cells in the atherosclerotic plaque.
Principles and Practice of Geriatric Psychiatry
Authors: Ira Katz
Journal: JAMA (2012)

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
Clinical Scintillation Scanning
Authors: E. James Potchen
Journal: JAMA (1969)

The rapid growth of nuclear medicine is largely due to our ability to map out the anatomic deposition of radionuclides. These scintiscanning techniques are uniquely useful in assessing some alterations in regional physiology. Although many recent books contain similar material,<i>Clinical Scintillation Scanning</i>is the most comprehensive text devoted entirely to this subject. An introductory chapter, well written by Dr. Benidict Cassen, who originated scintiscanning, places the field in historic perspective. Subsequent chapters discuss radiopharmaceuticals, instruments, organ-imaging techniques, and their clinical applications. Each major scanning technique is presented in a systematic manner. The chapter on radiopharmaceuticals is an outstanding contribution and ranks with the best written on that subject. Although clearly written, the chapter on instruments is too esoteric to be appreciated by the physician for whom it was intended. The appendix contains radiopharmaceutical tables which bring together information previously found only in scattered sources. The book has a major
Phospholipase C-mediated hydrolysis of phosphatidylcholine is activated by cis-diamminedichloroplatinum(II).
Authors: K Nishio, Y Sugimoto, Y Fujiwara, T Ohmori, T Morikage, Y Takeda, M Ohata, N Saijo
Journal: Journal of Clinical Investigation (1992)

We have investigated the effect of cis-diamminedichloroplatinum(II) (CDDP) on signal transduction pathways. CDDP treatment did not cause any change in the binding of [3H]-phorbol dibutyrate to PC-9 (human lung adenocarcinoma cell line) cells, a measure of protein kinase C activation. However, 2-h CDDP treatment (20 micrograms/ml) caused approximately 200% increase in 1,2-sn-diacylglycerol (DAG) production and approximately 50% decrease in inositol 1,4,5-triphosphate production. To explore the different source of DAG, we analyzed phospholipids labeled with [14C]choline by TLC and revealed that [14C]choline-labeled phosphatidylcholine (PC) was decreased to 50% by CDDP treatment. This suggested that PC turnover was increased by CDDP-treatment. PC-specific phospholipase C (PC-PLC) activity was increased to 2.5-fold (2.58 +/- 0.28 nmol/mg protein per min) by 2 h CDDP (20 micrograms/ml) treatment compared with control (1.05 +/- 0.24 nmol/mg protein per min). Treatment of CDDP also stimulated PC-PLC in the crude membrane extract from PC-9 cells. CDDP had no effect on the activities of phospholipase A2 and D. Trans-DDP, which has far less cytotoxicity than its stereoisomer, CDDP, did not cause any change in PC-PLC activity. A significant inhibition of DNA synthesis (less than 80%) occurred 4 h after 2 h CDDP (20 micrograms/ml) treatment. These results demonstrated that CDDP-induced PC-PLC activation was an early event in CDDP-induced cytotoxicity and suggested that the effects of CDDP on signal transduction pathways had an important role in CDDP-induced cytotoxicity.
Military Concern with Myoglobinuria
Authors: EUGENE L. GITIN
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 October 1972Military Concern with MyoglobinuriaEUGENE L. GITIN, MICHAEL A. DEMOS, JESSE F. ADAMSEUGENE L. GITINSearch for more papers by this author, MICHAEL A. DEMOSSearch for more papers by this author, JESSE F. ADAMSSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-4-659_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: As indicated by Hamilton and associates in their July 1972 article (p. 77) on exercise-induced myoglobinuria, the syndrome of acute exertional rhabdomyolysis is of particular interest to physicians dealing with military recruits. We would like to point out that the physicians of the U.S. Navy Medical Corps (particularly those charged with the medical care of the U.S. Marine Corps) are very concerned with this problem. Several articles by Navy physicians about this syndrome (O'Donnell in theAmerican Journal of Medicine;Gitin and Demos inMilitary Medicine) have been accepted for publication and will be in print soon.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Naval Medical Field Research Laboratory Camp Lejeune, N.C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByExertional RhabdomyolysisCase Report of Exertional Rhabdomyolysis in a 12-Year-Old Boy 1 October 1972Volume 77, Issue 4Page: 659-659KeywordsArmed forcesMilitary medicineRhabdomyolysis Issue Published: 1 October 1972 PDF DownloadLoading ...
Tuberculosis After Jejunoileal Bypass for Obesity
Authors: Jack R. Pickleman
Journal: JAMA (1975)

JEJUNOILEAL bypass has proved to be an effective means of achieving weight loss in morbidly obese individuals refractory to less drastic weight reduction measures. Widespread acceptance of this treatment, however, has been limited by early and remote complications related to the surgical procedure or the catabolic state induced. Electrolyte deficits of calcium, magnesium, and potassium, vitamin deficiencies, oxalate kidney stones and gallstone formation are some of the well-recognized metabolic sequelae.<sup>1,2</sup>Equally disturbing have been the reports of progressive fatty infiltration of the liver, sometimes culminating in cirrhosis.<sup>3-6</sup>Recently we became aware of two patients in whom tuberculosis developed after jejunoileal bypass surgery. This complication has not been previously reported, to our knowledge. Two hundred jejunoileal bypass patients were available for study at the Loyola University Medical Center and its affiliated hospitals. All patients had been operated on at least six months previously and had been seen regularly since
Tiapamil, a new calcium antagonist: hemodynamic effects in patients with acute myocardial infarction.
Authors: H G Eichler, T A Mabin, P J Commerford, E A Lloyd, W Beck, L H Opie
Journal: Circulation (1985)

The afterload reduction and myocardial oxygen sparing that results after administration of calcium antagonists suggests a possible role for these drugs in intervention after onset of acute myocardial infarction, but their use in this setting is limited by the possibility that left ventricular failure will develop. Tiapamil is a new verapamil congener. The hemodynamic effects of this drug (1 mg/kg followed by 25 micrograms/kg/min over 36 hr) were studied in 30 patients randomly assigned in a double-blind manner to a tiapamil or control group within 12 hr of the onset of acute myocardial infarction as diagnosed by Swan-Ganz catheterization and gated blood pool scans. Tiapamil reduced heart rate from 83 +/- 20 beats/min (mean +/- SD) before to 74 +/- 19 beats/min after drug (over an average 36 hr), arterial pressure from 128 +/- 22/87 +/- 14 to 118 +/- 16/74 +/- 11 mm Hg, rate-pressure product from 10,695 +/- 3492 to 8800 +/- 2550 units, and systemic vascular resistance from 1732 +/- 351 to 1400 +/- 350 dynes X sec X cm-5. Tiapamil also increased stroke volume index from 34.7 +/- 12.1 to 41.6 +/- 12.0 ml/m2, left ventricular ejection fraction from 50.1 +/- 14.8% to 56.4 +/- 17.4% (at 24 hr), left ventricular end-diastolic volume index from 71.3 +/- 23.1 to 80.5 +/- 23.7 ml/m2, and peak diastolic filling rate (an index of diastolic relaxation) from 2.1 +/- 0.9 to 2.6 +/- 0.8 end-diastolic volumes/sec (p less than .05 for all changes). Cardiac index, wedge pressure, left ventricular end-systolic volume, and PR interval remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
Contraceptive vaccine research: still an art
Authors: E. R. Gonzalez
Journal: JAMA (1980)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Malaria Therapy: The Value of the Randomized Controlled Trial
Authors: Michael Phillips
Journal: JAMA (1993)

<h3>To the Editor.</h3> —The fascinating story of malariotherapy for neurosyphilis holds important lessons for any investigator contemplating a trial of a new treatment for the acquired immunodeficiency syndrome (AIDS).<sup>1</sup>Clearly, there is a battle going on: randomized controlled trials (RCTs) vs chaos. Right now, chaos seems to be winning. The problem may be even worse than it appears: undocumented gossip in New York City has it that some AIDS patients enrolled in RCTs now hold clandestine meetings where they pool their tablets in order to equalize their chances of receiving an experimental new drug. I suggest that there may be a pathway through this problem that should be acceptable to clinical researchers as well as to AIDS patients seeking the best possible treatment. Part of the problem may lie in outdated perceptions of what constitutes a valid RCT. In a conventional RCT, a patient who gives informed consent is
THE CAUSAL RELATION OF BLOOD POVERTY TO GASTRIC ULCER: WITH REPORT OF AN ILLUSTRATIVE CASE WITH ATYPICAL SYMPTOMS.
Authors: ROBERT N. WILLSON
Journal: JAMA (1902)

As there is perhaps no subject the etiology of which has been so thoroughly thrashed over as that of gastric ulcer, and with so little final satisfaction in the way of a definite conclusion, it may not prove uninteresting to consider the condition with reference to a case that presents strong evidence of an actual causal systemic condition. Although traumatic as well as tubercular and syphilitic ulcers, and similar lesions of the stomach, are infrequent phenomena, when they do occur their etiology is clear because of known existing conditions. The characteristic peptic ulcer, or, as it might be well named, the pyloric ulcer, from its frequent occurrence in this position, gives, however, only a hint as to its causation; and the best writers on the subject satisfy themselves with the statement that in all probability a lesion of the mucous membrane has been present, followed by self-digestion of the gastric
Effect of Certain Anti-Arthritic Compounds on the Permeability of Synovial Membrane in the Rabbit
Authors: G. W. G. Sharp
Journal: Annals of the Rheumatic Diseases (1963)

Little is known of the pathogenesis of rheumatoid arthritis.The disease has many characteristics of infection, but no causative agent has been dis- covered.The situation is confused and hyper- sensitivity, auto-immunity, metabolic abnormality, and endocrine imbalance have all been suggested as possible causes, with or without a precipitating infectious or stress phase.One approach to the elucidation of this problem, which has only been possible in recent years, is to seek for common mechanisms of action in drugs exerting a beneficial effect on the course of the disease.The essential changes produced by these compounds must be, at least in part, the reverse of those brought about by the disease.Assessment of beneficial effect is difficult in rheumatoid arthritis, but many workers believe that cortisone, cortisol, and similar synthetic steroids, gold, salicylates, chloroquine, and phenyl- butazone all exert some favourable effect, while reports from Italy suggest that chlorpromazine may also be useful.These are markedly different chemically and therefore suited for this type of comparative pharmacological study.The effect of these compounds on the permeability of synovial membrane was studied for several reasons.For instance, the first detectable change in an inflammatory state is an increase in per- meability followed by exudation of fluid, oedema,
A COMPARATIVE STUDY OF SELECTED ANTIDEPRESSANT MEDICATIONS AND EST
Authors: MILTON GREENBLATT, GEORGE H. GROSSER, HENRY WECHSLER
Journal: American Journal of Psychiatry (1962)

The effectiveness of 3 antidepressant medications was compared with that of EST in 128 depressed hospitalized patients at 3 state mental hospitals. The results of this double blind study employing 4 different measures of treatment outcome present a consistent trend. They indicate that: 1. In this sample, the 4 treatments produced 50% marked improvement, 25% moderate improvement, and only 25% minimal improvement or lack of response. Although the absolute number of patients in the 3 hospitals differed, no appreciable deviation from this distribution was found in any of the 3 institutions. 2. There was no difference in treatment outcome between the 33 males and the 95 females. However, patients in the 16-39 age group showed more marked improvements than older patients. In addition, exogenous depressions responded significantly better to the 4 somatic treatments than schizo-affective and endogenous patients. 3. Patients treated with EST manifest a higher degree of improvement than patients treated with the 3 antidepressant medications. Specifically, a higher proportion of EST patients improved markedly than patients on drugs. In terms of symptom remission, decrease of depressive affect, and decrease in behavioral disturbance, EST patients in general fared better than the other patients. However, this was significant in all cases only in comparison to patients treated with isocarboxazid. Patients treated with imipramine revealed on several of the measures higher degrees of improvement than patients treated with the 2 MAO inhibitors. 4. When EST patients were compared with all drug patients to study selectivity of the 2 somatic treatments, it was found that younger patients, male patients, and patients with exogenous and schizo-affective depressions appeared to do as well on drugs as on EST. In the case of females, older patients, and endogenous depressions, EST showed significantly more marked results than the antidepressant medications. 5. The 4 measures were very consistent in revealing this pattern of results, with one exception: phenelzine appeared to show a higher degree of effectiveness as measured by the global ratings of outcome than as measured by the 3 quantitative indices. More cases will be required to account for this discrepancy. In other respects, the 3 quantitative measures showed very high intercorrelations, and were strongly related to the qualitative ratings of treatment outcome. 6. A relatively low frequency of side effects was recorded during the course of the study. These were largely of a transient nature, and not dose related.
Neurofibromatosis in pregnancy
Authors: GARDEN H. SWAPP, ROBERT A. MAIN
Journal: British Journal of Dermatology (1973)

Journal Article Neurofibromatosis in pregnancy Get access GARDEN H. SWAPP, GARDEN H. SWAPP Department of Obstetrics and Gynaecology Aberdeen Maternity Hospital, and Department of Dermatology Aberdeen Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar ROBERT A. MAIN ROBERT A. MAIN Department of Obstetrics and Gynaecology Aberdeen Maternity Hospital, and Department of Dermatology Aberdeen Royal Infirmary Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 88, Issue 5, 1 May 1973, Pages 431–435, https://doi.org/10.1111/j.1365-2133.1973.tb15445.x Published: 01 May 1973 Article history Accepted: 27 October 1972 Published: 01 May 1973
Human-derived neural progenitors functionally replace astrocytes in adult mice
Authors: Hong Chen, Kun Qian, Wei Chen, Baoyang Hu, Lisle W. Blackbourn, Zhongwei Du, Lixiang Ma, Huisheng Liu, Karla M. Knobel, Melvin Ayala, Su-Chun Zhang
Journal: Journal of Clinical Investigation (2015)

Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair.