tbuckley/cabot-search huggingface dataset:
A piece of my mind. Second childhood
Authors: A. Wagner
Journal: JAMA (1995)

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
Phase I Study of RGB-286638, A Novel, Multitargeted Cyclin-Dependent Kinase Inhibitor in Patients with Solid Tumors
Authors: Diane A.J. van der Biessen, Herman Burger, Peter de Bruijn, Cor H.J. Lamers, Nicole Naus, Hannes Loferer, Erik A.C. Wiemer, Ron H.J. Mathijssen, Maja J.A. de Jonge
Journal: Clinical Cancer Research (2014)

Abstract Purpose: RGB-286638 is a multitargeted inhibitor with targets comprising the family of cyclin-dependent kinases (CDK) and a range of other cancer-relevant tyrosine and serine/threonine kinases. The objectives of this first in human trial of RGB-286638, given i.v. on days 1 to 5 every 28 days, were to determine the maximum tolerated dose (MTD) and to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of this new drug. Experimental Design: Sequential cohorts of 3 to 6 patients were treated per dose level. Blood, urine samples, and skin biopsies for full PK and/or PD analyses were collected. Results: Twenty-six patients were enrolled in 6-dose levels from 10 to 160 mg/d. Four dose-limiting toxicities were observed in 2 of the 6 patients enrolled at the highest dose level. These toxicities were AST/ALT elevations in 1 patient, paroxysmal supraventricular tachycardias (SVTs), hypotension, and an increase in troponin T in another patient. The plasma PK of RGB-286638 was shown to be linear over the studied doses. The interpatient variability in clearance was moderate (variation coefficient 7%–36%). The PD analyses in peripheral blood mononuclear cells, serum (apoptosis induction) and skin biopsies (Rb, p-Rb, Ki-67, and p27KIP1 expression) did not demonstrate a consistent modulation of mechanism-related biomarkers with the exception of lowered Ki-67 levels at the MTD level. The recommended MTD for phase II studies is 120 mg/d. Conclusions: RGB-286638 is tolerated when administered at 120 mg/d for 5 days every 28 days. Prolonged disease stabilization (range, 2–14 months) was seen across different dose levels. Clin Cancer Res; 20(18); 4776–83. ©2014 AACR.
Abstract 2429: Temporally and spatially inducible mouse model of aneuploidy
Authors: Daniel Eichberg, Kristin Knouse, Angelika Amon
Journal: Cancer Research (2014)

Abstract Aneuploidy, the state in which cells have an abnormal number of chromosomes, is a hallmark of most human cancers. Despite aneuploidy's near-ubiquitous presence in tumors, it is unknown whether aneuploidy is a driver or passenger in cancer progression. Aneuploidy is normally prevented by the spindle assembly checkpoint (SAC), a critical cellular mechanism which blocks chromosomal missegregation by inhibiting premature sister chromatid separation during mitosis. Although transgenic mouse models with defective SAC proteins exist, the dysfunctional proteins are expressed constitutively from birth in all tissues, a milieu that differs from that of an in vivo human tumor in which cancer cells develop aneuploidy de novo in the context of a euploid organism. In order to generate a mouse model that more closely approximates this tumor environment, we will insert single copies of shRNA hairpins that target SAC proteins BubR1 or Mad2 into the mouse genome at the Col1A1 locus using recombination mediated cassette exchange. shRNA expression will be under the control of a tetracycline responsive element in tissues that co-express rtTA, leading to temporally and spatially inducible disruption of the SAC, and thus aneuploidy. In vitro shRNA construct validation experiments indicate our shRNAs successfully knockdown target RNA and protein levels, as well as functionally promote mitotic slippage after nocodazole arrest, which is indicative of an impaired SAC. We will use this mouse model to investigate the role of increased chromosomal missegregation on tumor initiation and evolution, as well as the impact of increased aneuploidy on normal organ function. [Daniel Eichberg is a Howard Hughes Medical Institute Medical Research Fellow.] Citation Format: Daniel Eichberg, Kristin Knouse, Angelika Amon. Temporally and spatially inducible mouse model of aneuploidy. [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 2429. doi:10.1158/1538-7445.AM2014-2429
Patients' reactions to their investigations: a study of 504 patients.
Authors: C Hawkins
Journal: BMJ (1979)

Five hundred and four patients who had undergone hospital investigations were interviewed to find out how much information they had been given about the tests; their reactions before, during and after the test; and any after effects. In 74% of cases the tests had been satisfactorily explained. Patients were told more about complicated procedures such as cardiac catherisation than about routine ones such as venepuncture or barium meal examinations. The comments doctors made while performing the investigations were generally reassuring and were only rarely worrying or impatient. About half the patients suffered pain or discomfort during the test and rather more complained of after effects. Only 5% of patients said they would refuse the test again, though 36% said they would agree only reluctantly. Communication lies at the heart of the problem. Hospitals should consider issuing handouts on investigations to back up the doctor9s information and to dispel myths. Staff should be more careful in concealing frightening-looking equipment, and if patients have to wait during investigations it may help reduce their anxiety if they are provided with something to occupy their time.
ABC of sexually transmitted diseases. Syphilis: diagnosis and management.
Authors: M W Adler
Journal: BMJ (1984)

Establishing a diagnosis of syphilis, whatever the stage of the disease, can be difficult and it is wise for all suspected cases to be referred for specialised tests and management in a department of genitourinary medicine.The diagnosis can be confirmed by the history, physical examination, and one or all of four tests-dark ground microscopy, serology, examination of cerebrospinal fluid, and radiology.Which of these tests appear as positive will depend on the clinical stage of the patient's syphilis.Dark ground microscopy Serological tests ~~~~~~~~~~~~~~~~~~~~~~~~~,
Pattern of Morphological Diversification in the Leptocarabus Ground Beetles (Coleoptera: Carabidae) as Deduced from Mitochondrial ND5 Gene and Nuclear 28S rDNA Sequences
Authors: Choong-Gon Kim, Hong-Zhang Zhou, Yûki Imura, Osamu Tominaga, Zhi-Hui Su, Syozo Osawa
Journal: Molecular Biology and Evolution (2000)

Most of the mitochondrial NADH dehydrogenase subunit 5 (ND5) gene and a part of nuclear 28S ribosomal RNA gene were sequenced for 14 species of ground beetles belonging to the genus Leptocarabus. In both the ND5 and the 28S rDNA phylogenetic trees of Leptocarabus, three major lineages were recognized: (1) L. marcilhaci/L. yokoae/Leptocarabus sp. from China, (2) L. koreanus/L. truncaticollis/L. seishinensis/L. semiopacus/L. canaliculatus/L. kurilensis from the northern Eurasian continent including Korea and Hokkaido, Japan, and (3) all of the Japanese species except L. kurilensis. Clustering of the species in the trees is largely linked to their geographic distribution and does not correlate with morphological characters. The species belonging to different species groups are clustered in the same lineages, and those in the same species group are scattered among the different lineages. One of the possible interpretations of the present results would be that morphological transformations independently took place in the different lineages, sometimes with accompanying parallel morphological evolution, resulting in the occurrence of the morphological species belonging to the same species group (=type) in the different lineages.
New antirejection drugs anticipated
Authors: T. Randall
Journal: JAMA (1990)

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
PBPK modeling/Monte Carlo simulation of methylene chloride kinetic changes in mice in relation to age and acute, subchronic, and chronic inhalation exposure.
Authors: R S Thomas, R S Yang, D G Morgan, M P Moorman, H R Kermani, R A Sloane, R W O'Connor, B Adkins, M L Gargas, M E Andersen
Journal: Environmental Health Perspectives (1996)

During a 2-year chronic inhalation study on methylene chloride (2000 or 0 ppm; 6 hr/day, 5 days/week), gas-uptake pharmacokinetic studies and tissue partition coefficient determinations were conducted on female B6C3F1, mice after 1 day, 1 month, 1 year, and 2 years of exposure. Using physiologically based pharmacokinetic (PBPK) modeling coupled with Monte Carlo simulation and bootstrap resampling for data analyses, a significant induction in the mixed function oxidase (MFO) rate constant (Vmaxc) was observed at the 1-day and 1-month exposure points when compared to concurrent control mice while decreases in glutathione S-transferase (GST) rate constant (Kfc) were observed in the 1-day and 1-month exposed mice. Within exposure groups, the apparent Vmaxc maintained significant increases in the 1-month and 2-year control groups. Although the same initial increase exists in the exposed group, the 2-year Vmaxc is significantly smaller than the 1-month group (p &lt; 0.001). Within group differences in median Kfc values show a significant decrease in both 1-month and 2-year groups among control and exposed mice (p &lt; 0.001). Although no changes in methylene chloride solubility as a result of prior exposure were observed in blood, muscle, liver, or lung, a marginal decrease in the fat:air partition coefficient was found in the exposed mice at p = 0.053. Age related solubility differences were found in muscle:air, liver:air, lung:air, and fat:air partition coefficients at p &lt; 0.001, while the solubility of methylene chloride in blood was not affected by age (p = 0.461). As a result of this study, we conclude that age and prior exposure to methylene chloride can produce notable changes in disposition and metabolism and may represent important factors in the interpretation for toxicologic data and its application to risk assessment.
Guilt by Association?
Authors: Samuel O. Thier
Journal: New England Journal of Medicine (1970)

Historically, aminoacidurias have been associated with mental disease. Enzymatic defects in amino acid metabolism, resulting in an accumulation of toxic substances or a deficiency of essential nutrients, may produce mental deficiency. Such cause- and-effect relations, however, were difficult to establish in many aminoacidurias originally reported in mentally retarded persons. It appeared as though many such associations resulted from the sampling bias of urine screening programs that were frequently carried out only in mental institutions. In this issue of the Journal (page 783) the report of an association between cystinuria and mental disease, when such an association was not orginally believed . . .
Management of heparin induced thrombocytopenia.
Authors: H N Magnani
Journal: BMJ (1993)

But having a motive is only one of the criteria for there being an active intention to bring about death.A second, and more compelling, criterion is that, in patients in a persistent vegetative state, death is certain since food is withdrawn.Perhaps one of the main reasons for moral unease in these cases is the inevitability of the ending of life (by withdrawal of food) when this cannot even be claimed to be in the patient's best interests since he or she is permanently insensate.The negative claim that since the patient lacks any best interests the doctor has no further duty to treat him or her does not seem a sufficient moral justification for ending life in this way.
Discrimination against people with HIVinfection and AIDS
Authors: C D'Andrea, E Vaccher, U Tirelli
Journal: BMJ (1994)

out, there should be continuity of treatment between the community and prison.2There has been considerable pressure to ensure that the delivery of methadone detoxification to opiate users presenting to prison is adequate, and guide- lines have been drawn up, with the cooperation of key people involved in drug treatment services, to promote this.Opiate users should be given sufficient methadone during drug withdrawal to reduce the likelihood of them injecting and using contaminated equipment.Ross and colleagues insist that the existing seven day withdrawal regimen is unethical.Colleagues and I run an inpatient unit where we provide a 10 day withdrawal regimen for all our opiate dependent patients, and we can see no grounds for arguing that reducing this to seven days is unethical or fails to replicate the physiological rates of withdrawal.3 4 In my view such withdrawal regimens should be spread evenly throughout the prison system.According to the most recent report of the director of health care for prisoners, a survey of prison treatment establishments found that only a fifth of respondents were providing methadone detoxification for opiate withdrawal.All prison medical officers should provide approved treat- ments for drug withdrawal; more individualised treatment approaches can evolve in the wake of the widespread provision of a basic minimum of treatment.'
Local statin therapy differentially interferes with smooth muscle and endothelial cell proliferation and reduces neointima on a drug-eluting stent platform
Authors: B JASCHKE, C MICHAELIS, S MILZ, M VOGESER, T MUND, L HENGST, A KASTRATI, A SCHOMIG, R WESSELY
Journal: Cardiovascular Research (2005)

Therapeutic strategies to provide local inhibition of mitogen mediated proliferation and migration of human coronary artery smooth muscle cells (CASMC) by means of drug-eluting stents have been shown to enable effective limitation of neointimal hyperplasia. However, currently available drug-eluting stents utilize compounds that may also adversely affect endothelial regrowth, thus possibly precipitating subsequent cardiac events. Accordingly, identification of compounds that differentially inhibit smooth muscle and endothelial cell migration and proliferation could be of substantial clinical usefulness.In addition to lipid lowering, statins are known to display auxiliary pleiotropic activities. The purpose of this study was to evaluate the effect of local administration of cerivastatin on proliferation, migration and cytotoxicity of CASMC as well as coronary artery endothelial cells (CAEC) and to evaluate the effect of cerivastatin-coated stents on the inhibition of neointima formation as well as endothelial regrowth within the stented vessel. Cerivastatin displayed a differential effect on CASMC as compared to CAEC with regard to proliferation and migration; both were more profoundly inhibited in CASMC. Appreciable cytotoxicity and pro-apoptotic effects were low in both cell lines at therapeutic concentrations. Cerivastatin-elution led to significant inhibition of neointima formation in the rat carotid stent model, endothelial coverage of in-stent vascular tissue was similar with control and cerivastatin-eluting stents.As proof of principle, our study provides evidence that local application of a HMG-CoA reductase inhibitor on a drug-eluting stent platform can efficiently limit neointima formation. Consequently, these compounds warrant further clinical evaluation to confirm this finding. Our data further suggest that the anti-restenotic effect of local statin administration might be associated with a more protective interaction with the endothelium than that observed with compounds currently employed on drug-eluting stents.
Complete Atrioventricular Block due to Cardiac Metastasis of Bronchogenic Carcinoma
Authors: GERALD D. BUCKBERG, NOBLE O. FOWLER
Journal: Circulation (1961)

A partial review of the literature indicates that the heart is not infrequently involved in patients who have malignant disease. The most common tumors metastasizing to the heart are bronchogenic carcinoma, breast carcinoma, malignant melanoma, and the group of hematopoietic malignant tumors. The clinical triad of myocardial insufficiency, cardiac arrhythmia, and pericardial effusion involving a previously normal heart should alert one to this possibility, especially in a patient with known malignant tumor. Complete atrioventricular block is a rather uncommon manifestation of metastatic cardiac tumor. A case is reported in which complete heart block appeared as the sole clinical manifestation of metastatic involvement of the heart by bronehogenic carcinoma. Necropsy revealed cardiac involvement by tumor to be virtually limited to the interventricular septum.
Immunohistochemical localization of chromostatin and pancreastatin, chromogranin A-Derived bioactive peptides, in normal and neoplastic neuroendocrine tissues
Authors: Noriko Kimura, Akihiro Funakoshi, Dominique Aunis, Kayoko Tateishi, Wakako Miura, Hiroshi Nagura
Journal: Endocrine Pathology (1995)
Your National Library of Medicine
Authors: Martin M. Cummings
Journal: JAMA (1975)

AMERICAN physicians have at their disposal an information resource unsurpassed by those available for other scientific disciplines—the National Library of Medicine (NLM). Although the library is located in Bethesda, Md, its collection of 1.5 million items is available to you through your local hospital, medical school, or other health science library. The NLM traces its origin back to 1836, when the Library of the Army Surgeon General's Office was established. Then, beginning in 1865 and continuing over a period of 30 years, Dr. John Shaw Billings, one of the truly remarkable men in American medicine, took this modest collection of medical works and built it into a great resource for American health professionals. Perhaps Billings' greatest achievement was the development of the<i>Index Medicus</i>(1879) and the monumental<i>Index-Catalogue</i>(1880). To this day descendants of these two works (the former still under its original title; the latter now known as
Regulation of DNA synthesis in fat cells and stromal elements from rat adipose tissue
Authors: C. H. Hollenberg, A. Vost
Journal: Journal of Clinical Investigation (1968)

The incorporation of tritiated thymidine into the deoxyribonucleic acid (DNA) of adipose fat and stromal cells was followed under a variety of conditions. After in vitro incubation of adipose slices or up to 2 days after in vivo injection of the isotope, all DNA radioactivity was in the stromal cell fraction. From 2 to 15 days after thymidine injection total tissue DNA radioactivity was constant, while between 2 and 5 days after injection label in fat cell DNA increased markedly. Thus new labeled fat cells, initially collected in the stromal pool, required 2-5 days after completion of DNA synthesis to accumulate sufficient lipid to be harvested in the fat cell fraction. Fasting before thymidine injection practically abolished DNA synthesis in primordial fat cells and reduced less drastically formation of stromal elements. However fasting sufficient to deplete lipid stores by 50% neither destroyed mature fat cells nor impaired their capacity to reaccumulate fat with refeeding. Other studies evaluated the role of new fat cell formation in the process of lipid accretion accompanying refeeding. These experiments indicated that at least during the early phase of rapid weight gain, accumulation of fat was due to deposition of triglyceride in existing cells rather than to accelerated formation of new fat cells. Studies with hypophysectomized rats demonstrated that pituitary ablation variably affected stromal DNA synthesis and nearly abolished the formation and (or) maturation of primordial fat cells. In these animals growth hormone markedly enhanced thymidine incorporation into stromal DNA but had no effect on fat cell precursors. In intact animals the predominant effect of growth hormone was also on the stromal fraction, although an action of the hormone of lesser magnitude on fat cell precursors was also evident.
Obituary Listing
Authors: Alan R. Nelson
Journal: JAMA (1998)

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