tbuckley/cabot-search huggingface dataset:
Abstract 4040: Age-related effects following exposure of bone marrow-derived mesenchymal stem cells to etoposide .
Authors: Ian Hare, Marieta Gencheva, Laura Gibson
Journal: Cancer Research (2013)

Abstract Mesenchymal stem cells (MSCs) have been shown to be one of the populations that support hematopoietic stem cell (HSC) development within the bone marrow microenvironment. High dose myelosuppressive or ablative chemotherapy regimens that are utilized prior to bone marrow transplantation have the potential to damage MSCs, consistent with damage which we have previously reported for more differentiated stromal and osteoblast cells. As with more differentiated progenitor cells, interactions between MSCs and HSCs are vital to hematopoietic homeostasis with alterations of these interactions having the potential to hamper hematopoietic reconstitution following treatment. In the current study we begin to investigate age associated differences in the vulnerability of the microenvironment to stress utilizing primary human MSCs from passages 6 to 10, characterized functionally by adipocytic and osteogenic differentiation and surface expression profiling (CD105+CD44+CD166+CD45−). We have shown that treatment of MSCs with 25μM etoposide for 24 hours in-vitro causes the occurrence of dsDNA breaks that recover within 48 hours following treatment. In addition, chemotherapy induced stress was followed by an induction of p21. Homologous recombination associated transcripts (XRCC2, XRCC3, Rad51) were reduced following etoposide treatment relative to non-homologous end joining associated transcripts (Ku70, Ku80, DNA-PK), and the magnitude of these differences was augmented with age in-vitro. Pro-apoptotic transcripts Puma and Noxa and the anti-apoptosis associated Bcl-XL showed induction with treatment while Bcl-2 decreased, suggesting the wide range of genes that are responsive to chemotherapy exposure. These results provide insight into the damage responses of MSCs to etoposide and how DNA repair capabilities following chemotherapy could be influenced by patient age. A more mechanistic understanding of the recovery pathways that are altered with age may be valuable for innovative approaches to the treatment of elderly patients for whom escalated chemotherapy is required in an effort to optimize microenvironment supported immune system recovery. Citation Format: Ian Hare, Marieta Gencheva, Laura Gibson. Age-related effects following exposure of bone marrow-derived mesenchymal stem cells to etoposide . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4040. doi:10.1158/1538-7445.AM2013-4040
Human Papilloma Virus E6 and E7 Proteins Support DNA Replication of Adenoviruses Deleted for the E1A and E1B Genes
Authors: Dirk S. Steinwaerder, Cheryl A. Carlson, André Lieber
Journal: Molecular Therapy (2001)

The action of transforming proteins from small DNA tumor viruses seems to be remarkably similar between different viruses, as they all use pRb and p53 pathways as cellular targets. This leads to deregulation of host cell cycling, which in turn creates an environment favorable for viral replication. Based on this, we hypothesized that regulatory proteins from human papillomaviruses (HPVs) can functionally trans-complement viral DNA replication of adenoviruses deleted for the E1A and E1B genes (AdE1−). To test this, we constructed AdE1− vectors expressing the human papilloma virus 16 (HPV-16) proteins E6 and E7. Expression of both E6 and E7 from these vectors partially complemented adenoviral DNA replication activity in vitro, in SK-Hep1 cells and primary human astrocytes, as well as in vivo in mouse liver. AdE1− vectors expressing E6 and E7 also increased hepatocellular DNA synthesis in vivo. Efficient AdE1− DNA replication was detected in HPV-associated cervical carcinoma cells but not in primary human cells. Linking the expression of regulatory oncoviral proteins to DNA replication of E1-mutant adenoviruses may provide a rationale for antitumor strategies.
Prolongation of canine pancreas allograft survival with cyclosporin A: preliminary report.
Authors: P McMaster, A Procyshyn, R Y Calne, R Valdes, K Rolles, D J Smith
Journal: BMJ (1980)

Studies were conducted on dogs to test the efficacy of cyclosporin A (CyA) in prolonging normoglycaemia and graft survival after whole-organ pancreas allograft transplantation. Five dogs subjected to pancreatectomy alone served as controls. Withholding immunosuppression after transplantation (five animals) resulted in the same median duration of survival as occurred in the controls (13 days). Azathioprine and steroids (seven animals) produced median durations of normoglycaemia and survival of 9 and 23 days respectively. Animals given CyA 18 mg/kg/day (five) and 25 mg/kg/day (10), however, showed median durations of normoglycaemia of 18 and 55 days (p less than 0.05 and p less than 0.02) respectively and median survival times of 36 and 85 days (NS and p less than 0.02). If CyA proved effective in controlling rejection of pancreas allografts in man it would offer unstable diabetics in renal failure a more hopeful outlook than conventional immunosuppression.
What If Patients With Dementia Use Decision Aids to Make an Advance Euthanasia Request?
Authors: Chris Gastmans, Yvonne Denier
Journal: The American Journal of Bioethics (2010)

Levi and Green (2010) successfully argue that the computerbased decision aid Making Your Wishes Known is an optimal instrument to ensure that a patient’s wishes concerning endof-life-care can be known and respected as much as possible. We agree that such an instrument can improve the quality of end-of-life care to an important extent. It can offer people real mental comfort, by allowing them to retain control of their end-of-life care, even after they have lost their decisionmaking capacity (Widdershoven and Berghmans 2001). Suppose, however, that Mrs. Klinger, the 78-year-old lady diagnosed with Alzheimer’s disease (Levi and Green 2010), lives in Amsterdam and uses the decision aid to develop an advance euthanasia directive. This could be a real-life possibility, since in the Netherlands, euthanasia in persons with severe dementia, as decreed in an advance euthanasia directive, is legally allowed. In such cases, life can be terminated (by administration of lethal drugs) when the dementia reaches a certain stage. In Belgium, bills have been put forward in the Parliament to follow the Dutch example. In this paper we point out what we believe are three pressing problems with the use of the decision aid in order to develop advance euthanasia directives.
Acute Rhabdomyolysis Associated with Cocaine Intoxication
Authors: D Roth, F J Alarcón, J A Fernandez, R A Preston, J J Bourgoignie
Journal: New England Journal of Medicine (1988)

Because an increasing number of patients were arriving at our emergency room with cocaine intoxication and rhabdomyolysis, we reviewed our experience with such patients. We identified 39 patients seen at our institution over an eight-year period with acute rhabdomyolysis after cocaine use. The patients' mean creatine kinase level was 12,187 U per liter (range, 1756 to 85,000). Thirteen of the 39 patients (33 percent) had acute renal failure; 6 of them died. In comparison to the patients with normal renal function, those with renal failure were more often admitted with profound hypotension (46 vs. 4 percent; P less than 0.001), hyperpyrexia (69 vs. 15 percent; P less than 0.001), and markedly elevated serum creatine kinase levels (mean, 28,084 vs. 7931 U per liter; P less than 0.01). Disseminated intravascular coagulation developed in seven patients with renal failure. All six deaths were in this group. Severe hepatic dysfunction was found in 11 patients with renal failure. We conclude that cocaine intoxication can cause acute rhabdomyolysis with acute renal failure, severe liver dysfunction, and disseminated intravascular coagulation and that the mortality rate among patients with this syndrome is high.
Epitope mapping of the von Willebrand factor subunit distinguishes fragments present in normal and type IIA von Willebrand disease from those generated by plasmin.
Authors: S D Berkowitz, J Dent, J Roberts, Y Fujimura, E F Plow, K Titani, Z M Ruggeri, T S Zimmerman
Journal: Journal of Clinical Investigation (1987)

A small but consistent proportion of the von Willebrand factor (vWF) in normal plasma is composed of 189, 176, and 140 kD fragments cleaved from the 225 kD subunit. A monoclonal antibody map of vWF, based on the reactivity of individual antibodies with cyanogen bromide and tryptic fragments of known carboxy and/or amino termini, showed that in normal and IIA von Willebrand disease (vWD) plasmas the 140 kD fragment was derived from the amino-terminal region, whereas the 176 kD fragment was derived from the carboxy-terminal region of the subunit. In type IIA vWD, however, the fragments comprised a greater proportion of circulating vWF. In contrast, plasmin cleaved a 176 kD fragment from the amino terminus and a 145 kD fragment from the carboxy terminus of the subunit. Species similar to these plasmin-cleaved fragments were demonstrated in plasmas from four patients treated with fibrinolytic agents, but not in IIA vWD.
Dietary Supplements—Regulatory Issues and Implications for Public Health
Authors: Bryan E Denham
Journal: JAMA (2011)

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
Hormonal contraceptives with ethinyl estradiol were associated with increased thrombotic stroke and MI
Authors: Jeff Andrews
Journal: Annals of Internal Medicine (2012)

ACP Journal Club16 October 2012Hormonal contraceptives with ethinyl estradiol were associated with increased thrombotic stroke and MIJeff Andrews, MD, FRCSCJeff Andrews, MD, FRCSCVanderbilt University, Nashville, Tennesee, USA (J.A.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-157-8-201210160-02009 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationLidegaard Ø, Løkkegaard E, Jensen A, Skovlund CW, Keiding N. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med. 2012;366:2257-66. https://pubmed.ncbi.nlm.nih.gov/22693997Clinical Impact RatingsHospitalists: Cardiology: Endocrinology: Reference1 Centers for Disease Control and Prevention. Reproductive health. Maternal and Infant Health. Pregnancy complications. www.cdc.gov/reproductivehealth/maternalinfanthealth/PregComplications.htm (accessed 21 Aug 2012). Google Scholar Author, Article, and Disclosure InformationAffiliations: Vanderbilt University, Nashville, Tennesee, USA (J.A.)This article was published at Annals.org on 2 October 2012. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 16 October 2012Volume 157, Issue 8Page: JC4-9KeywordsContraceptivesEstradiolMyocardial infarctionOophorectomyPregnancyRisk managementStroke ePublished: 16 October 2012 Issue Published: 16 October 2012 CopyrightCopyright © 2012 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
siRNA delivery from triblock copolymer micelles with spatially-ordered compartments of PEG shell, siRNA-loaded intermediate layer, and hydrophobic core
Authors: Hyun Jin Kim, Kanjiro Miyata, Takahiro Nomoto, Meng Zheng, Ahram Kim, Xueying Liu, Horacio Cabral, R. James Christie, Nobuhiro Nishiyama, Kazunori Kataoka
Journal: Biomaterials (2014)
Safety and efficacy of velaglucerase alfa in Gaucher disease type 1 patients previously treated with imiglucerase
Authors: Ari Zimran, Gregory M. Pastores, Anna Tylki‐Szymanska, Derralynn A. Hughes, Deborah Elstein, Rebecca Mardach, Christine Eng, Laurie Smith, Margaret Heisel‐Kurth, Joel Charrow, Paul Harmatz, Paul Fernhoff, William Rhead, Nicola Longo, Pilar Giraldo, Juan A. Ruiz, David Zahrieh, Eric Crombez, Gregory A. Grabowski
Journal: American Journal of Hematology (2012)

Velaglucerase alfa is a glucocerebrosidase produced by gene activation technology in a human fibroblast cell line (HT-1080), and it is indicated as an enzyme replacement therapy (ERT) for the treatment of Gaucher disease type 1 (GD1). This multicenter, open-label, 12-month study examined the safety and efficacy of velaglucerase alfa in patients with GD1 previously receiving imiglucerase. Eligible patients, ≥2 years old and clinically stable on imiglucerase therapy, were switched to velaglucerase alfa at a dose equal to their prior imiglucerase dose. Infusion durations were 1 hr every other week. Forty patients received velaglucerase alfa (18 male, 22 female; four previously splenectomized; age range 9-71 years). Velaglucerase alfa was generally well tolerated with most adverse events (AEs) of mild or moderate severity. The three most frequently reported AEs were headache (12 of 40 patients), arthralgia (9 of 40 patients), and nasopharyngitis (8 of 40 patients). No patients developed antibodies to velaglucerase alfa. There was one serious AE considered treatment-related: a grade 2 anaphylactoid reaction within 30 min of the first infusion. The patient withdrew; this was the only AE-related withdrawal. Hemoglobin concentrations, platelet counts, and spleen and liver volumes remained stable through 12 months. In conclusion, adult and pediatric patients with GD1, previously treated with imiglucerase, successfully transitioned to velaglucerase alfa, which was generally well tolerated and demonstrated efficacy over 12 months' treatment consistent with that observed in the velaglucerase alfa phase 3 clinical trial program.
Effect of Prolonged Steroid Therapy for Rheumatic Fever on the Exchangeable Potassium Content and Body Weight
Authors: JERRY K. AIKAWA, Aaron J. Blumberg
Journal: Circulation (1957)

Serial measurements of the body weight and exchangeable potassium content were made in 13 children with acute rheumatic fever who were being treated with large doses of corticotropin or cortisone. In 8 subjects the clinical signs of hyperadrenalism developed. Seven of the 13 subjects showed at least a 20 per cent increase in body weight, which could not be explained on the basis of changes in the body's exchangeable potassium content. This weight gain is thought to be due to an increase in total body fat.
The American Blood Commission
Authors: ROBERT G. CHAPMAN
Journal: Annals of Internal Medicine (1975)

Editorial Notes1 July 1975The American Blood CommissionROBERT G. CHAPMAN, M.D., F.A.C.P.ROBERT G. CHAPMAN, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-83-1-115_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe American Blood Commission (ABC), inaugurated in April 1975, developed from a unique approach by the federal government to coordinate and improve our nation's blood-banking activities. Instead of forming another government agency, the Department of Health, Education, and Welfare invited the private sector to form an agency of its own (1). Behind this invitation was the certainty that if the private organizations failed to develop something suitable, the government would do so itself. Without this pressure, it is doubtful that organizations such as the American Association of Blood Banks and the American National Red Cross, with their divergent approaches to...References1. National blood policy. Fed Regist 39:32702-32711, 10 September 1974 Google Scholar2. SURGENOR D: Progress toward a national blood system. N Engl J Med 291:17-22, 1974 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Belle Bonfils Memorial Blood Center Denver, Colorado PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1975Volume 83, Issue 1Page: 115-115KeywordsAvidin biotin complexBloodBlood banks Issue Published: 1 July 1975 PDF DownloadLoading ...
Glyburide or Insulin for Metabolic Control in Non-Insulin-Dependent Diabetes Mellitus
Authors: DAVID M. NATHAN
Journal: Annals of Internal Medicine (1988)

Study Objective: To compare the relative efficacy, risks, and benefits of insulin with glyburide in achieving normoglycemia in non-insulin-dependent diabetes mellitus. Design: Randomized, double-blind, placebo-controlled trial with a 9-month treatment period. Setting: University hospital. Patients: Thirty-one patients with non-insulin-dependent diabetes mellitus who did not have normal glucose control with diet alone. Interventions: Once-per-day NPH insulin and placebo glyburide, or glyburide and once-per-day placebo insulin injection. Active drug and placebo adjusted in parallel to achieve fasting plasma glucose level less than 6.4 mmol/L (115 mg/dL) without hypoglycemia. Measurements and Main Results: Insulin and glyburide produced similar improvement in fasting blood glucose levels and hemoglobin A1c concentrations, similar frequencies of mild symptomatic hypoglycemia, and similar weight gain despite dietary reinforcement. Triglyceride and cholesterol levels decreased and high-density lipoprotein cholesterol and ratios of high-density lipoprotein to total cholesterol increased in both groups, with a significantly greater improvement in high-density lipoprotein cholesterol and ratio of high-density lipoprotein total cholesterol in patients treated with insulin. Conclusions: Therapy with glyburide or once-per-day NPH insulin provides a similar degree of glucose control in patients with non-insulin-dependent diabetes mellitus. Insulin may have a relative advantage in that it is associated with higher levels of high-density lipoprotein cholesterol and a higher ratio of high-density lipoprotein to total cholesterol.
Toxoplasmic Encephalitis in Patients With Acquired Immune Deficiency Syndrome
Authors: Benjamin J. Luft
Journal: JAMA (1984)

An epidemic of cases of toxoplasmic encephalitis is occurring in patients with acquired immune deficiency syndrome (AIDS). Serological or histopathologic studies were performed on 70 cases with AIDS and toxoplasmic encephalitis. In many cases conventional stains of brain-tissue specimens failed to disclose Toxoplasma organisms; all were positive when stained by the peroxidase-antiperoxidase technique. Except for a single patient, serological titers were not indicative of an acute acquired infection. The ratio of titers in the agglutination test to titers in the Sabin-Feldman dye test seemed to be more predictive of active toxoplasmic encephalitis in patients with AIDS than either test alone. Based on histological and serological data, an approach is presented for diagnosis and treatment of suspected toxoplasmic encephalitis in patients with AIDS.
FDG PET/CT Findings of a Glomangiopericytoma
Authors: Gary R. Conrad, Partha Sinha, Kimberly J. Absher
Journal: Clinical Nuclear Medicine (2011)

Glomangiopericytoma (GPC) is a rare vascular neoplasm that arises almost exclusively from the nasal cavity or paranasal sinuses. GPC is also called sinonasal-type hemangiopericytoma, although current nomenclature, as well as classification in a group with myopericytomas, better emphasizes the relatively indolent behavior of this tumor. The authors present the FDG PET/CT findings of GPC in a 53-year-old with symptoms of nasal congestion and facial pressure. CT and MRI showed a nasal mass to extend along the sphenoid ridge from the posterior nasal cavity into the posterior nasopharynx. PET showed the mass to have uniformly low-grade FDG hypermetabolism. Pathologic examination of the surgical specimen showed classic features of GPC.
Comparative inhalation teratogenicity of four glycol ether solvents and an amino derivative in rats.
Authors: B K Nelson, J V Setzer, W S Brightwell, P R Mathinos, M H Kuczuk, T E Weaver, P T Goad
Journal: Environmental Health Perspectives (1984)

Previous research demonstrated the inhalation teratogenicity of the solvent 2-ethoxyethanol in rats and rabbits. As this is one of a class of widely used industrial solvents, we investigated the teratogenicity of five structurally related compounds. Each chemical was vaporized and administered to approximately 15 pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects. Data were analyzed on a litter basis; three solvents were compared with a pooled group (N = 34) of sham-exposed controls, and the remaining two were compared with a group of 15 controls. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occurred at both 100 and 50 ppm. 2-ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. In summary, shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether, both patterns predictable from the biochemical literature.
Vaginal Absorption of Povidone-Iodine
Authors: Helmuth Vorherr
Journal: JAMA (1980)

In 12 nonpregnant women, total iodine, protein-bound iodine, inorganic iodine, and thyroxine values were measured in serum before and 15, 30, 45, or 60 minutes after a two-minute vaginal disinfection with povidone-iodine (Betadine). Only 15 minutes after application, serum iodine levels were raised and remained significantly elevated 30, 45, and 60 minutes after disinfection. Serum concentrations of total iodine and inorganic iodine were increased up to fivefold to 15-fold, respectively; during the relative short period of observation, thyroxine levels were not altered. An overload of iodine can suppress thyroid hormonogenesis, and the fetal and neonatal thyroid glands are especially sensitive. In pregnant women, vaginitis should not be treated with povidone-iodine because of the possible development of iodine-induced goiter and hypothyroidism in the fetus and newborn. The risk is especially high when povidone-iodine is used repeatedly. (<i>JAMA</i>1980;244:2628-2629)