tbuckley/cabot-search huggingface dataset:
Insulin-like Growth Factor–Binding Protein-7 Functions as a Potential Tumor Suppressor in Hepatocellular Carcinoma
Authors: Dong Chen, Byoung Kwon Yoo, Prasanna Kumar Santhekadur, Rachel Gredler, Sujit K. Bhutia, Swadesh K. Das, Christine Fuller, Zao-zhong Su, Paul B. Fisher, Devanand Sarkar
Journal: Clinical Cancer Research (2011)

Hepatocellular carcinoma (HCC) is a highly virulent malignancy with no effective treatment, thus requiring innovative and effective targeted therapies. The oncogene astrocyte-elevated gene-1 (AEG-1) plays a seminal role in hepatocarcinogenesis and profoundly downregulates insulin-like growth factor-binding protein-7 (IGFBP7). The present study focuses on analyzing potential tumor suppressor functions of IGFBP7 in HCC and the relevance of IGFBP7 downregulation in mediating AEG-1 function.IGFBP7 expression was detected by immunohistochemistry in HCC tissue microarray and real-time PCR and ELISA in human HCC cell lines. Dual FISH was done to detect LOH at IGFBP7 locus. Stable IGFBP7-overexpressing clones were established in the background of AEG-1-overexpressing human HCC cells and were analyzed for in vitro proliferation and senescence and in vivo tumorigenesis and angiogenesis.IGFBP7 expression is significantly downregulated in human HCC samples and cell lines compared with normal liver and hepatocytes, respectively, and inversely correlates with the stages and grades of HCC. Genomic deletion of IGFBP7 was identified in 26% of patients with HCC. Forced overexpression of IGFBP7 in AEG-1-overexpressing HCC cells inhibited in vitro growth and induced senescence, and profoundly suppressed in vivo growth in nude mice that might be an end result of inhibition of angiogenesis by IGFBP7.The present findings provide evidence that IGFBP7 functions as a novel putative tumor suppressor for HCC and establish the corollary that IGFBP7 downregulation can effectively modify AEG-1 function. Accordingly, targeted overexpression of IGFBP7 might be a potential novel therapy for HCC.
HIV and Human Trafficking–Related Stigma
Authors: Ramona Vijeyarasa, Richard A. Stein
Journal: JAMA (2010)

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
The Humanization of Medicine
Authors: Lester S. King
Journal: JAMA (1975)

Medicine is becoming more and more dehumanized as machines and apparatus take over the tasks of diagnosis and therapy. The laboratory, the x-ray, the computer, the various invasive techniques are increasingly important in what we fondly call scientific medicine. As machines encroach more and more on the practice of medicine, we tend to lose sight of the<i>person</i>. The doctor-patient relationship, always the object of lip service, gets obscured in the welter of diagnostic tests. Yet perhaps the very complexity of modern scientific medicine, in a sort of backlash, is serving to focus attention on personal involvement, not merely between doctor and patient, but between doctor and patient and society. Some problems of the person have in the past few years received considerable attention in the lay and professional press, particularly those problems that we call ethical—abortion, euthanasia, transplantation, human experimentation, genetic engineering, and the like. These topics go far
A MEMORABLE PATIENT
Authors: E. Downes
Journal: BMJ (1995)

It is a little disconcerting to walk into a gynaecology ward hearing a hysterical woman scream, “You're trying to murder my little girl.” It was even more disconcerting to realise that she had been admitted under my consultant's care. Soon the story unfolded. A 28 year old woman with a long history of primary subfertility had been admitted with six weeks' amenorrhoea, lower abdominal pain, and light vaginal bleeding. An ultrasound scan could not find any evidence of an intrauterine pregnancy and we were trying to …
Airway Epithelial Cell Responses to Ozone Injury
Authors: George D. Leikauf, Leigh G. Simpson, Jeffrey Santrock, Qiyu Zhao, Joan Abbinante-Nissen, Shaoying Zhou, Kevin E. Driscoll
Journal: Environmental Health Perspectives (1995)

The airway epithelial cell is an important target in ozone injury.Once activated, the airway epithelium responds in three phases.The initial, or immediate phase, involves activation of constitutive cells, often through direct covalent interactions including the formation of secondary ozonolysis prod- ucts-hydroxyhydroperoxides, aldehydes, and hydrogen peroxide.Recently, we found hydroxyhydroperoxides to be potent agonists of bioactive eicosanoid formation by human airway epithelial cells in culture.Other probable immediate events include activation and inactivation of enzymes present on the epithelial surface (e.g., neutral endopeptidase).During the next 2 to 24 hr, or early phase, epithelial cells respond by synthesis and release of chemotactic factors, including chemokines-macrophage inflammatory protein-2, RANTES, and interleukin-8.Infiltrating leukocytes during this period also release elastase, an important agonist of epithelial cell mucus secretion and additional chemokine formation.The third (late) phase of ozone injury is characterized by eosinophil or monocyte infiltration.Cytokine expression leads to alteration of structural protein synthesis, with increases in fibronectin evident by in situ hybridization.Synthesis of epithelial antiproteases, e.g., secretary leukocyte protease inhibitor, may also increase locally 24 to 48 hr after elastase concentrations become excessive.Thus, the epithelium is not merely a passive barrier to ozone injury but has a dynamic role in directing the migration, activating, and then counteracting inflammatory cells.Through these complex interactions, epithelial cells can be viewed as the initiators (alpha) and the receptors (omega) of ozone-induced airway disease.
IgE and its related phenomena in bullous pemphigoid
Authors: H. SOH, H. HOSOKAWA, Y. ASADA
Journal: British Journal of Dermatology (1993)

This study was designed to analyse IgE and its related phenomena in bullous pemphigoid (BP). We analysed 17 BP sera by indirect immunofluorescence (IIF) and immunoblotting (IB) using a monoclonal antibody to IgE. In addition, inflammatory cells in lesional skin from 11 patients with BP were analysed by the alkaline phosphatase-anti-alkaline phosphatase (APAAP) technique using monoclonal antibodies to IgE and Fc epsilon RII/CD23. IgE class anti-basement membrane zone (BMZ) autoantibody was detected in nine of 17 sera (52.9%) by IIF. IgG class anti-BMZ antibody could block the BMZ-binding reactivity of IgE class antibody. Titres of IgE class autoantibody in the sera ranged from 1:40 to 1:320, and statistically correlated with serum IgE levels. Two of 11 sera contained an IgE class autoantibody which recognized a 230-kDa BP antigen by IB. By radio-allergosorbent test (RAST), IgE-specific antibodies to an extended series of common inhalant and food allergens were detectable in six sera with high concentrations of total IgE (over 3,300 IU/ml). IgE-bearing and Fc epsilon RII-expressing cells were demonstrated in the upper dermis and along the BMZ in seven of 11 biopsy specimens by the APAAP technique. The distribution and number of IgE-bearing cells in the lesions were similar to those of the Fc epsilon RII-expressing cells. These results suggest that both IgE-mediated immune responses and autoimmunity characterize BP as distinctive features.
400 NUCLEOSIDE ANALOGUES ALONE OR COMBINED WITH VACCINATION PREVENT WHV INFECTION AND INDUCE PROTECTIVE IMMUNITY: NEW STRATEGY FOR HBV POST-EXPOSURE PROPHYLAXIS
Authors: B. Wang, Z. Zhu, B. Zhu, Z. Song, S. Huang, W. Fan, Y. Tao, Z. Wang, H. Wang, M. Lu, D. Yang
Journal: Journal of Hepatology (2013)
The Better Care Fund: a disaster in waiting?
Authors: N. Hawkes
Journal: BMJ (2014)

Although the fund is a worthwhile aspiration, confusion exists at almost every level



Some projects in the NHS in England start well and then go sour—think of Connecting for Health. Others, despite being makeshift, at least put a poultice on a painful boil—the Cancer Drugs Fund, for example. And then there are those that sound good on paper, tick enough of the right boxes to face no intellectual challenge, but nevertheless look like a disaster in waiting from their very inception. Here is where we find the Better Care Fund.

The idea is to take some money from acute care trusts and give it to local authorities to be spent in providing better health and social services in the community, thereby preventing so many admissions that hospitals won’t even notice the loss of income. It seeks a virtuous circle of fewer admissions and faster discharges, easing pressure on the acute sector while providing care in the places patients are supposed to want it—a worthwhile aspiration.

But there is confusion at almost every level. The transfers involved, totalling £3.8bn (€4.7bn; $6.4bn), are large enough to destabilise many acute trusts but too small to replenish the losses local authorities have suffered in the years of retrenchment since 2010. …
Degradation of circulating DNA by extracorporeal circulation over nuclease immobilized on nylon microcapsules.
Authors: D S Terman, A Tavel, T Tavel, D Petty, R Harbeck, G Buffaloe, R Carr
Journal: Journal of Clinical Investigation (1976)

Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody.
Changes in performance of the surviving myocardium after left ventricular infarction in rats
Authors: J. G. Mill, I. Stefanon, C. M Leite, D. V Vassallo
Journal: Cardiovascular Research (1990)

Study objective – The aim was to investigate left ventricular performance of infarcted hearts during scar formation and development of hypertrophy in the surviving myocardium. Design – Hearts were perfused according to the Langendorff technique and left ventricular function curves were obtained by inserting a distensible balloon into the ventricular cavity. The isovolumetric systolic pressure was measured as diastolic pressure was changed from 0 to 25 mm Hg and during inotropic interventions produced by Ca and isoprenaline. Experimental materials – Hearts were obtained from albino rats of either sex, 180–250 g, killed 1, 3, 7 or 14 d after left coronary artery ligation (n = 24) or sham operation (n = 26). Normal rats (n = 6) were used as additional controls. Measurements and main results – After infarction, there was a progressive and almost parallel displacement of the ventricular function curves toward higher diastolic pressures. The positive chronotropic response to isoprenaline was similar in infarcted and non-infarcted hearts. The inotropic response to Ca and isoprenaline, however, was significantly depressed in the infarcted hearts throughout the observation period. Conclusions – Hypertrophy in the surviving myocardium did not result in improvement of the left ventricular systolic function assessed under in vitro conditions during the first two weeks after infarction. The decreased inotropic response of the infarcted left ventricle to isoprenaline is likely to be dependent on the reduced Ca sensitivity of the surviving myocardium.
A clinical trial of CTLA-4 blockade with tremelimumab in patients with hepatocellular carcinoma and chronic hepatitis C
Authors: Bruno Sangro, Carlos Gomez-Martin, Manuel de la Mata, Mercedes Iñarrairaegui, Elena Garralda, Pilar Barrera, Jose Ignacio Riezu-Boj, Esther Larrea, Carlos Alfaro, Pablo Sarobe, Juan José Lasarte, Jose L. Pérez-Gracia, Ignacio Melero, Jesús Prieto
Journal: Journal of Hepatology (2013)
PTH-041 A High Quality Transient Elastography Service Can Successfully Be Delivered By Healthcare Assistants
Authors: I Patanwala, S Fielding, K Akerboom, J Barr, T Cross, M Lombard, P Richardon, H Caldwell
Journal: Gut (2014)

<h3>Introduction</h3> Surrogate assessment of liver fibrosis by means of liver stiffness measurement (LSM) by transient elastography is well validated in different cohorts of patients with liver disease and is now a part of routine hepatological practice. There is an increasing demand for LSM in view of its role in managing patients with dermatological or haematological conditions who are on potentially fibrogenic therapy. Referrals for LSM in our unit have increased significantly over the last 12 months. Traditionally, specialist liver nurses have been trained to deliver this service. However, LSM by transient elastography is an easily transferable skill and therefore in a bid to reduce waiting times and make the service as cost effective as possible, we trained healthcare assistants (HCA) to perform LSMs. The aim of this review was to assess the impact of this change on the quality of LSM as measured by success rate and failed scans. <h3>Methods</h3> A transient elastography service delivered by trained specialist liver nurses was set up in our hospital in May 2010. In July 2013, 3 HCAs were trained to carry out LSM using a Fibroscan®. The HCAs were initially trained by the manufacturers of the Fibroscan<sup>®</sup> unit (Echosens Europe) and then underwent a period of formally observed training with formative and summative work place based assessments. After competency was ascertained, the HCAs were independently allowed to carry out LSMs. A retrospective review of all LSM reports from January 2013 to December 2013 was carried out and success rate of the tests were recorded. Any repeat requests due to failure were also recorded. <h3>Results</h3> A total of 876 LSM were performed during the review period. 542 LSMs were performed by trained nurses and 334 by trained HCAs. There was no statistically significant difference in the mean success rate between nurses (96% SD 11.9%) and HCAs (96.4% SD 11.7%) (p = 0.699, 2 sample T Test) nor the proportion of LSMs with 100% success rates between the two groups (78.4 vs. 82.3% p = 0.151, Fisher’s exact test). Furthermore, there were no statistical differences in any central measure of the observed interquartile ranges of the reported LSM between the 2 groups (p = 0.255). No LSM was repeated when performed by HCA for reasons of failure. <h3>Conclusion</h3> LSM using a Fibroscan<sup>®</sup> can be accurately performed by appropriately trained HCAs. The introduction of this change in practice has allowed a reduction in waiting time for LSM to within 2 weeks without affecting the quality of the service and allowed a more efficient use of resources. A high quality transient elastography service can be delivered by HCAs. <h3>Disclosure of Interest</h3> None Declared.
Screening for the small-for-dates fetus.
Authors: J P Neilson, C R Whitefield, T Aitchison
Journal: BMJ (1980)

Size of tumour and operation performed in relation to length of history, 1979 Short* Intermediate Longt history history history No of inoperable tumours 1 2 7 Average tumour diameter (cm) 16 2-6 3-1 No of mastectomies 19 29 8 No of wide local excisions 16 22 1 Total No of patients 36 53 16*Short history .onemonth.tLong history-one year.radiotherapy.The selection of patients for conservative surgery is on the basis of the relative volume of the tumour to the breast and on its position.Patients with central tumours still undergo mastectomy but patients with relatively small medial or lateral tumours have wide local excision.If wide local excision and postoperative radiotherapy can control local disease as effectively as mastectomy, then our message to the public is not that shorter delay neces- sarily means longer survival but that shorter delay means less radical surgery.
Prognostic Factors for Cure, Recurrence and Long-Term Survival After Surgical Resection of Thymoma
Authors: Najib Safieddine, Geoffrey Liu, Kris Cuningham, Tsao Ming, David Hwang, Anthony Brade, Andrea Bezjak, Stefan Fischer, Wei Xu, Sassan Azad, Marcelo Cypel, Gail Darling, Kazu Yasufuku, Andrew Pierre, Marc de Perrot, Tom Waddell, Shaf Keshavjee
Journal: Journal of Thoracic Oncology (2014)
Renal arterial disease and accelerated hypertension.
Authors: E Montuschi
Journal: BMJ (1977)

Dr Slater is wrong when he states that "Wright3 estimated that a 1°C rise in tempera- ture will increase the estimated blood alcohol concentration by 6.5o/o."Careful scrutiny of Wright's paper shows that he made no such claim.However, in the same proceedings Dubowski4 stated that "it may be well to point out that each 1°C increase in actual alveolar breath exit temperature between 34°C and 37°C would tend to increase a blood alcohol concentration calculated on the basis of an assumed 1:2100 ratio by about 6 50 over the actual level.
Dominance of hepatitis C virus (HCV) is associated with lower quantitative hepatitis B surface antigen and higher serum interferon-γ-induced protein 10 levels in HBV/HCV-coinfected patients
Authors: S.B. Wiegand, J. Jaroszewicz, A. Potthoff, C. Höner zu Siederdissen, B. Maasoumy, K. Deterding, M.P. Manns, H. Wedemeyer, M. Cornberg
Journal: Clinical Microbiology and Infection (2015)
Treatment Failure After Substitution of Generic Pancrelipase Capsules
Authors: Arthur J. Haymes
Journal: JAMA (1990)

<h3>To the Editor.—</h3> The report of treatment failure after substitution of generic pancrelipase capsules<sup>1</sup>clearly illustrates the need for regulatory oversight in the manufacture of enteric-coated dosage forms. The Food and Drug Administration categorizes enteric-coated formulations as "pharmaceutical alternates" and not "pharmaceutical equivalents" because these products differ in some aspect of formulation. Accordingly, the Food and Drug Administration does not evaluate the bioequivalency of pharmaceutical alternates in its list of therapeutically equivalent drug products,<sup>2</sup>in part due to the lack of systematic comparisons on which evaluation could be based. Pharmaceutical alternates (same drug, different formulation) constitutes a gray area between generic alternates (same drug, same formulation, different manufacturer) and therapeutic alternates (different drug). In addition to enteric-coated products, other types of pharmaceutical alternates include different dosage forms (tablets, capsules, and liquids), derivatives of the same active ingredient (esters, salts, acids, and bases), sustained-release formulations that use different technologies
Conditional Deletion of Insulin-like Growth Factor-I Receptor in Prostate Epithelium
Authors: Brent W. Sutherland, Sue E. Knoblaugh, Paula J. Kaplan-Lefko, Fen Wang, Martin Holzenberger, Norman M. Greenberg
Journal: Cancer Research (2008)

Abstract Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that can influence growth, differentiation, and survival of cells expressing the cognate type 1 receptor (IGF-IR). To better understand cell autonomous IGF-IR signaling in the epithelial compartment of the prostate gland, we generated a conditional (Cre/loxP) prostate-specific IGF-IR knockout mouse model. In contrast to epidemiologic studies that established a correlation between elevated serum IGF-I and the risk of developing prostate cancer, we show that abrogation of IGF-IR expression in the dorsal and lateral prostate could activate extracellular signal-regulated kinase 1/2 signaling and cause cell autonomous proliferation and hyperplasia. Moreover, persistent loss of IGF-IR expression in dorsal and ventral lobes induced p53-regulated apoptosis and cellular senescence rescue programs, predicting that titration of IGF-IR signaling might facilitate growth of tumors with compromised p53 activity. Therefore, we crossed the mice carrying the prostate-specific IGF-IR knockout alleles into the transgenic adenocarcinoma of the mouse prostate model that is driven, in part, by T antigen–mediated functional inactivation of p53. Consistent with our prediction, prostate epithelial–specific deletion of IGF-IR accelerated the emergence of aggressive prostate cancer when p53 activity was compromised. Collectively, these data support a critical role for IGF-IR signaling in prostate tumorigenesis and identify an important IGF-IR–dependent growth control mechanism. [Cancer Res 2008;68(9):3495–504]