tbuckley/cabot-search huggingface dataset:
Abstract 4473: Sorafenib suppresses postsurgical recurrence and metastasis of hepatocellular carcinoma in an orthotopic mouse model
Authors: Yu-Xiong Feng, Jiang-Sha Zhao, Jing-Jing Li, Dong Xie
Journal: Cancer Research (2011)

Abstract Surgical resection is the first-line treatment for hepatocellular carcinoma (HCC) patients with well-preserved liver function. Nevertheless, postoperative recurrences occur up to 70% at 5 years, gravely jeopardizing the therapeutic outcome. Clearly, new approaches are needed for preventing relapse of this deadly disease. Taking advantage of a luciferase-labeled orthotopic xenograft model of HCC, we examined the role of Sorafenib, the first approved systemic drug for advanced HCC patients, in prevention of HCC recurrence. We found that Sorafenib suppressed the development of postsurgical intrahepatic recurrences, as well as abdominal metastasis, consequently leading to a prolonged postoperative survival of mice in this model. Furthermore, hyperactivity of ERK signaling caused by elevated levels of growth factors associated with postoperative liver regeneration enhanced the sensitivity of HCC cells to Sorafenib, providing a plausible explanation to the observation that recurrent tumors are more responsive to growth inhibition by Sorafenib. Our results strongly suggest a potential application of Sorafenib in early stage HCC patients who have received hepatectomy with curative intention, by effectively reducing postoperative recurrences. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4473. doi:10.1158/1538-7445.AM2011-4473
SPECIFIC THROMBOXANE SYNTHETASE INHIBITION AND ALBUMIN EXCRETION RATE IN INSULIN-DEPENDENT DIABETES
Authors: A.H. Barnett, B.A. Leatherdale, A. Polak, M. Toop, K. Wakelin, J.R. Britton, J. Bennett, D. Rowe, K. Dallinger
Journal: The Lancet (1984)
Plasma Catecholamines in Stress and Exercise
Authors: Joel E. Dimsdale
Journal: JAMA (1980)

A technique was devised to monitor plasma catecholamines in a minimally obtrusive fashion in subjects going about their working activities. There was a disparity between plasma norepinephrine and epinephrine levels in different situations. During public speaking, epinephrine levels increase twofold, whereas during physical exercise, norepinephrine levels increase threefold. It seemed that while exercise induces a response of the sympathetic nervous system, psychological stress induces primarily an adrenal response.
Insulin resistance and tnf alpha polymorphism in Italian patients with non alcoholic fatty liver disease (NAFLD)
Authors: Silvia Fargion, Luca Valenti, Anna Ludovica Fracanzani, Anna Scaccabarozzi, Paola Dongiovanni, Filippo Numeroso, Gennaro Santorelli, Adriana Branchi, Gemino Fiorelli
Journal: Journal of Hepatology (2001)
Human leukocyte antigen class II associations with hepatitis C virus clearance and virus‐specific CD4 T cell response among Caucasians and African Americans
Authors: Rebecca A. Harris, Kazushi Sugimoto, David E. Kaplan, Fusao Ikeda, Malek Kamoun, Kyong‐Mi Chang
Journal: Hepatology (2008)

The outcome of hepatitis C virus (HCV) infection has been associated with antiviral CD4 T cell response, human leukocyte antigens (HLA) class II genotypes, and ethnicity. However, HLA class II molecules restrict the nature of CD4 T cell response, and HLA distributions differ between ethnic groups. In this study, we asked whether HLA class II genotypes associated with HCV clearance are shared between Caucasian and African Americans and whether they contribute to enhanced antiviral CD4 T cell response. In a cohort of 93 HCV-seropositive subjects from Northeast America with defined ethnicity, virological outcome, and HCV-specific CD4 T cell proliferation, we confirm the previously reported associations between HCV clearance and two HLA types (DQB1*03, DRB1*11) while identifying a new association with DRB3*02. Strikingly, these associations were identified only among Caucasian [DQB1*03: odds ratio (OR), 10.4; P = 0.031, DRB1*11: OR, 7.0, P = 0.019; DRB3*02: OR, 8.3, P = 0.005; DQB1*03–DRB3*02: OR, 13.5, P = 0.001) but not among African American patients. Furthermore, although HLA DQB1*03, DRB1*11, and DRB3*02 genotypes were associated with increased HCV-specific CD4 T cell response in univariate analyses, these associations were lost when controlling for virological outcomes. Conclusion: We conclude that the immunogenetic basis for HCV clearance differs between ethnic groups and that the association between HLA class II and HCV clearance is not directly explained by antiviral CD4 T cell response. (HEPATOLOGY 2008.)
HOME CARE AND THE PRACTITIONER
Authors: E. M. Bluestone
Journal: JAMA (1952)

To the Editor:  —The establishment of an extramural hospital activity, popularly known as home care, is under serious consideration in many hospitals of this country and abroad. Though we now have a considerable literature on the subject based on a highly successful experiment, there still remain some misgivings in the minds of practitioners about the influence of such a program on their work.  Home care has been received enthusiastically by the profession of social service (a dream come true). These workers, closely related to the practice of medicine, have been left holding the bag when they were informed that the physician has come to the end of the resources at his immediate disposal. Home care has been an accepted though very limited tradition with the nursing profession. Only the physician's consent is required to speed the program on its way. With the approval and cooperation of organized medicine, this plan
Smoking Areas Are Ineffective in Sick Buildings
Authors: Louis C. Kossuth
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The Feb 28 issue of<i>JAMA</i>seemed excellent until I reached the editorial on page 1051. In telling what the American Medical Association had done at its home office, the editorial revealed that the American Medical Association has been trapped by the fallacy that designation of smoking areas prevents pollution of the air by tobacco smoke in the building. Unless there is special air-handling equipment, the nonsmoking areas will be polluted by the air that is recirculated from the smoking areas. Equally important, the invisible tobacco smoke air pollution increases throughout the day. In a modern building designed with the usual heating, air-conditioning, and ventilating equipment, there is a continuous recirculation of the air in the building. This results in workers suffering from the "tight building syndrome"<sup>1</sup>or the "sick building syndrome."<sup>2</sup> The problem is that unless adequate fresh air is introduced into the system,
Prospective assessment of renal histopathological lesions in patients with end-stage liver disease: Effects on long-term renal function after liver transplantation
Authors: Yvon Calmus, Filoména Conti, Philippe Cluzel, Gary Hill, Corinne Antoine, Olivier Scatton, Olivier Soubrane, Denis Glotz, Evangéline Pillebout, Dominique Nochy
Journal: Journal of Hepatology (2012)
Leptin regulation of Hsp60 impacts hypothalamic insulin signaling
Authors: André Kleinridders, Hans P.M.M. Lauritzen, Siegfried Ussar, Jane H. Christensen, Marcelo A. Mori, Peter Bross, C. Ronald Kahn
Journal: Journal of Clinical Investigation (2013)

Type 2 diabetes is characterized by insulin resistance and mitochondrial dysfunction in classical target tissues such as muscle, fat, and liver. Using a murine model of type 2 diabetes, we show that there is hypothalamic insulin resistance and mitochondrial dysfunction due to downregulation of the mitochondrial chaperone HSP60. HSP60 reduction in obese, diabetic mice was due to a lack of proper leptin signaling and was restored by leptin treatment. Knockdown of Hsp60 in a mouse hypothalamic cell line mimicked the mitochondrial dysfunction observed in diabetic mice and resulted in increased ROS production and insulin resistance, a phenotype that was reversed with antioxidant treatment. Mice with a heterozygous deletion of Hsp60 exhibited mitochondrial dysfunction and hypothalamic insulin resistance. Targeted acute downregulation of Hsp60 in the hypothalamus also induced insulin resistance, indicating that mitochondrial dysfunction can cause insulin resistance in the hypothalamus. Importantly, type 2 diabetic patients exhibited decreased expression of HSP60 in the brain, indicating that this mechanism is relevant to human disease. These data indicate that leptin plays an important role in mitochondrial function and insulin sensitivity in the hypothalamus by regulating HSP60. Moreover, leptin/insulin crosstalk in the hypothalamus impacts energy homeostasis in obesity and insulin-resistant states.
Monoclonal Antibody Blockade of the Human Eag1 Potassium Channel Function Exerts Antitumor Activity
Authors: David Gómez-Varela, Esther Zwick-Wallasch, Hendrik Knötgen, Araceli Sánchez, Thore Hettmann, Dmitri Ossipov, Rüdiger Weseloh, Constanza Contreras-Jurado, Mike Rothe, Walter Stühmer, Luis A. Pardo
Journal: Cancer Research (2007)

The potassium channel ether à go-go has been directly linked to cellular proliferation and transformation, although its physiologic role(s) are as of yet unknown. The specific blockade of human Eag1 (hEag1) may not only allow the dissection of the role of the channel in distinct physiologic processes, but because of the implication of hEag1 in tumor biology, it may also offer an opportunity for the treatment of cancer. However, members of the potassium channel superfamily are structurally very similar to one another, and it has been notoriously difficult to obtain specific blockers for any given channel. Here, we describe and validate the first rational design of a monoclonal antibody that selectively inhibits a potassium current in intact cells. Specifically blocking hEag1 function using this antibody inhibits tumor cell growth both in vitro and in vivo. Our data provide a proof of concept that enables the generation of functional antagonistic monoclonal antibodies against ion channels with therapeutic potential. The particular antibody described here, as well as the technique developed to make additional functional antibodies to Eag1, makes it possible to evaluate the potential of the channel as a target for cancer therapy.
Artifacts associated with the measurement of oxidized DNA bases.
Authors: J Cadet, T Douki, J L Ravanat
Journal: Environmental Health Perspectives (1997)

In this paper we review recent aspects of the measurement of oxidized DNA bases, currently a matter of debate. There has long been an interest in the determination of the level of oxidized bases in cellular DNA under both normal and oxidative stress conditions. In this respect, the situation is confusing because variations that may be as large as two orders of magnitude have been reported for the yield of the formation of 8-oxo-7,8-dihydroguanine (8-oxoGua) in similar DNA samples. However, recent findings clearly show that application of several assays like gas chromatography-mass spectrometry (GC-MS) and -32P--postlabeling may lead to a significant overestimation of the level of oxidized bases in cellular DNA. In particular, the silylation step, which is required to make the samples volatile for the GC-MS analysis, has been shown to induce oxidation of normal bases at the level of about one oxidized base per 10(4) normal bases. This has been found to be a general process that applies in particular to 8-oxoGua, 8-oxo-7, 8-dihydroadenine,5-hydroxycytosine, 5-(hydroxymethyl)uracil, and 5-formyluracil. Interestingly, prepurification of the oxidized bases from DNA hydrolysate prior to the derivatization reaction prevents artefactual oxidation. Under these conditions, the level of oxidized bases measured by GC-MS is similar to that obtained by HPLC associated with electrochemical detection (HPLC-EC). It should be added that the level of 8-oxo-7,8-dihydro-2;-deoxyguanosine in control cellular DNA has been found to be about fivefold lower than in earlier HPLC-EC measurements by using appropriate conditions of extraction and enzymatic digestion of DNA. Similar conclusions were reached by measuring formamidopyrimidine-DNA glycosylase sensitive sites as revealed by the single cell gel electrophoresis (comet) assay.
Lenalidomide for the Treatment of B-Cell Malignancies
Authors: Asher A. Chanan-Khan, Bruce D. Cheson
Journal: Journal of Clinical Oncology (2008)

Lenalidomide is a novel anticancer agent that has made a major impact in the treatment of patients with B-cell malignancies. A more potent analog of thalidomide, lenalidomide was developed to enhance immunomodulatory properties with improved safety profile. Its antitumor activity seems mediated through modulation of both the cytokine and cellular tumor cell microenvironment. Preclinical as well as clinical observations demonstrate that lenalidomide downregulates production of various critical prosurvival cytokines in the tumor microenvironment while concurrently promoting activation of T- and natural killer (NK) cell-mediated antitumor response. Early clinical investigations noted its efficacy in relapsed and/or refractory multiple myeloma patients. Subsequently, larger randomized studies confirmed the clinical benefit of lenalidomide when added to dexamethasone compared with dexamethasone alone in previously treated myeloma patients resulting in its recent approval by the US Food and Drug Administration. Consequently, the role of lenalidomide in other B-cell malignancies has been investigated, with impressive results in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. This review summarizes the data from various clinical investigations and highlights the impact of lenalidomide in the management of patients with B-cell malignancies.
Vitamin A and the susceptibility of respiratory tract tissues to carcinogenic insult.
Authors: P Nettesheim, C Snyder, J C Kim
Journal: Environmental Health Perspectives (1979)

The influence of vitamin A on the development of chemically induced lung carcinomas in rats was investigated.Rats were maintained on low, "normal" and excess levels of retinyl acetate (RA).Respira- tory tract-squamous carcinomas were induced by intratracheal injections of 3-methylcholanthrene (3-MCA).The carcinogen doses used ranged from 1.25 to 10.0 mg of 3-MCA.Serial sacrifices conducted during the first 20 weeks following carcinogen exposure showed that metaplastic lung nodules, presumed to be precursors of later appearing carcinomas, occurred earlier and at a higher incidence in rats maintained on low levels of RA than in rats maintained on moderate or high levels of RA.The development of invasive pulmonary carcinomas was enhanced at all four carcinogen doses in rats receiving low levels of RA as compared to rats receiving moderate or high levels of RA.No consistent difference in lung cancer incidence existed between the groups receiving normal and high levels of RA.The data clearly show an increased susceptibility of vitamin A-deficient rats to develop chemically induced lung cancers.Possible mechanisms underlying this effect are discussed.
Is Nitroglycerin a Novel and Inexpensive Treatment for Osteoporosis?
Authors: Sundeep Khosla
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 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
Mishap or Malpractice?
Authors: John C. Kruse
Journal: JAMA (1986)

Mishap or Malpractice , by Clifford Hawkins, a physician in Birmingham, England, serves to strip away the parochial views that we in the United States tend to have toward our malpractice problems. Although a lawyer in England referred to malpractice as the American disease, it is a worldwide problem with common roots. The value of this book is a fresh perspective.  The occasion of this book was the centenary of the Medical Defense Union (MDU) of Great Britain. The MDU was formed originally by two solicitors and five gentlemen for the purpose of defending physicians against improper attacks in the courts by the public. The first case involved allegations of a sexual assault on a drugged patient. The MDU rapidly grew into a more comprehensive society under the guidance of Mr Lawson Tait, a pioneer in the field of abdominal surgery.  The present MDU affords counsel to physicians and dentists by
Sex differences in pain: And now for something completely different
Authors: Ron Kupers
Journal: Behavioral and Brain Sciences (1997)

The belief that women report more somatic complaints than men is not new. Many centuries b.c., the Egyptians and the Greeks already made an association between female pains and hysteria, which is Greek for “wandering womb.” Despite the commonly held belief that women are more sensitive to pain than men, the issue of sex differences in pain has received little attention from the scientific community in general. It is the merit of berkley to draw our attention to this large gap in our scientific knowledge.
Comparative Pharmacokinetics and Serum Bactericidal Activities (SBA) of Ciprofloxacin (C) and Ofloxacin (O) Following Single Dose (Oral [PO] and Intravenous [IV])
Authors: M.P. Weinstein, R.M. Echols, S.F. Kowalsky, None PharmD, A.H. Heller
Journal: Drugs (1993)
A Physical and Physiological Basis for the Interpretation of Cardiac Auscultation: Evaluations Based Primarily on the Second Sound and Ejection Murmurs
Authors: Leon Resnekov
Journal: JAMA (1982)

Alas for phonocardiography, now relegated to memories of its glorious past. Its apparatus is now largely and ignominiously gathering dust in out-of-the-way corners. This gloomy scenario, although common, is not always followed, fortunately, since a proper appreciation of the role of phonocardiography can teach so much about the art of auscultation and the meaning of heart sounds. It is therefore refreshing to have available Dr Paul B. Stein's monograph on the physical and physiological fundamentals of so much that is taken for granted in auscultation and the basis for which is so often poorly understood. The volume details a series of elegant experiments painstakingly undertaken by the author and his colleagues over the last decade and longer. All the studies have already been published in appropriate journals, and it is useful to have the series collected in one volume. Emphasis is placed on the factors responsible for creating the second
Public Health Effects of Occupational and Environmental Radiation Exposure-Reply
Authors: William R. Hendee
Journal: JAMA (1991)

In Reply.  —Wing et al 1 report a radiation-cancer mortality dose  that is 10 times  than estimates from A-bomb survivors. They state ... measures of exposure to external penetrating radiation were related to death from all cancers and all causes to a greater degree than would be expected from the radiation epidemiology literature. Yet, the authors wish to distinguish higher dose response from higher cancer mortality, even though the dose  referenced is cancer mortality. There may well be confusion, but it is not with the interpretation of the article as referenced in my editorial. 2   The data in this paper are sensational because they depart significantly from the existing extensive database on radiation effects in humans. Sensationalized media coverage is a natural consequence of publishing such data. What else did the authors expect?
The prince and the professor: Which emperor is naked?
Authors: John P Briffa
Journal: BMJ (2004)

<h3>BACKGROUND</h3> Although behavioural treatment (biofeedback) successfully treats the pelvic floor abnormalities in patients with idiopathic constipation, many patients also normalise their impaired bowel frequency. We postulated that a response may be associated with altered cerebral outflow via extrinsic autonomic nerves to the gut. We investigated whether treatment changes extrinsic innervation, using mucosal laser Doppler flowmetry, whether autonomic changes are gut specific, and whether it changes gut transit. <h3>MATERIALS AND METHODS</h3> Forty nine patients (44 female, mean age 39 years) with idiopathic constipation were studied before and after biofeedback treatment (mean five sessions). Rectal mucosal blood flow was measured by laser Doppler flowmetry to assess direct extrinsic gut nerve autonomic activity. To assess general autonomic activity, RR (interval between successive R waves on the electrocardiogram) variability, Valsalva ratio, orthostatic adjustment ratio, and phase II:IV blood pressure ratio (II:IV) of the Valsalva manoeuvre were measured. All autonomic tests were compared with those of 26 healthy volunteers (19 female, mean age 37 years). <h3>RESULTS</h3> Twenty nine of 49 patients were symptomatically improved. Treatment reduced those with ⩽3 bowel actions per week (27 <i>v</i> 9, pre<i>v </i>post), need to strain (26<i>v</i> 9), and laxative or suppository use (34<i>v</i> 9). Biofeedback reduced retained markers by 32% in those with slow transit and by 20% in those with normal transit. Twenty two had slow transit before treatment—14 felt symptomatic improvement of whom 13 developed normal transit. There was a significantly greater increase in rectal mucosal blood flow in patients who subjectively improved compared with those who did not (29%<i>v</i> 7%; p&lt;0.03) and in those with improved bowel frequency (33% <i>v</i> 9%, increased<i>v</i> unchanged bowel frequency; p&lt;0.05). Thirty five patients had abnormal RR variability and 33 an abnormal Valsalva ratio; one had an abnormal orthostatic adjustment ratio and one an abnormal II:IV ratio. None of the general cardiorespiratory autonomic reflexes was changed by treatment. <h3>CONCLUSIONS</h3> Biofeedback treatment affects more than the pelvic floor. Successful outcome after biofeedback treatment is associated with improved activity of the direct cerebral innervation to the gut and improved gut transit. This effect is gut specific; cardiovascular autonomic reflexes were not altered.