tbuckley/cabot-search huggingface dataset:
777. A Novel Pan-Oncolytic Adenovirus Therapeutically Effective in Different Cancer Cell Types
Authors: Maria V. Lopez, Diego Viale, Eduardo G. Cafferata, Daniela R. Macio, David Gould, Yuti Chernajovsky, Osvaldo L. Podhajcer
Journal: Molecular Therapy (2006)

SPARC is a matricellular protein that is overexpressed in malignant and stromal components of human melanomas. We have previously shown that a 1.3 Kb SPARC promoter region was effective in driving suicide gene expression both in melanoma and endothelial cells leading to the elimination of melanoma tumors in vivo in nude mice suggesting that SPARC promoter could be a good candidate for generating a conditional replicating oncolytic adenovirus. By using luciferase expression as a reporter gene, we performed a detailed analysis of the activity and specificity of different fragments of SPARC promoter. We selected a promoter sequence extending from –512 bp to +35 bp, named F512, that showed the best ratio of activity vs. specificity in human melanoma cells compared to human cervix, breast and colon carcinoma cell lines. We constructed two adenoviral vectors in which the E1A gene was driven by F512. Ad-F512 lacks the E3 region while Ad-I-F512-E3 has an intact E3 region and an insulator sequence between the ITR and F512. The lytic capacity of both viruses was initially tested in vitro on a panel of malignant cells, melanoma (n=3), colon (n=2), breast (n=3) and cervix (n=1); and normal cells (bone marrow derived cells, WI-38 fibroblasts and BAEC endothelial cells). Unexpectedly, both adenoviruses were equally efficient in inducing lysis of SPARC-expressing and non-expressing malignant cells. In general, malignant cells that were sensitive or resistant to wild type Ad5 lytic effect were also sensitive or resistant to both recombinant viruses lytic effect. Interestingly, colon cancer cells became more sensitive than melanoma cells to the recombinant viruses. In addition, both viruses showed 3 to 5 logs lower lytic capacity in normal cells than wild type Ad5. Thus, CRAds based on SPARC promoter seem to replicate specifically in cancer cells while preserving normal cells. Ad-F512 was able to complement cell spreading of an E1-E3- replication defective vector expressing b-galactosidase indicating that this virus could be combined with non replicative therapeutic adenovirus. Finally, nude mice harboring SB2 melanoma tumors (mean 120 mm3) were treated intratumoraly with three administrations of 1010 vp/mouse of Ad-F512 or Ad-I-F512-E3. The treatment resulted in a potent antitumor effect. In 3 out of 5 mice, the tumor was completely eliminated, and one mouse showed a slight tumor growth, while in mice treated with control Ad-b-gal virus we observed no therapeutic benefit. These results indicate that both Ad-F512 and Ad-I-F512-E3 selectively replicate in and eliminate a panel of cancer cells and subcutaneous tumors, suggesting that they might be useful as pan-oncolytic viruses.
Effect of offering different levels of support and free nicotine replacement therapy via an English national telephone quitline: randomised controlled trial
Authors: J. Ferguson, G. Docherty, L. Bauld, S. Lewis, P. Lorgelly, K. A. Boyd, A. McEwen, T. Coleman
Journal: BMJ (2012)

<b>Objective</b> To compare the effects of free nicotine replacement therapy or proactive telephone counselling in addition to standard smoking cessation support offered through a telephone quitline. <b>Design</b> Parallel group, 2×2 factorial, randomised controlled trial. <b>Setting</b> National quitline, England. <b>Participants</b> 2591 non-pregnant smokers aged 16 or more residing in England who called the quitline between February 2009 and February 2010 and agreed to set a quit date: 648 were each randomised to standard support, proactive support, or proactive support with nicotine replacement therapy, and 647 were randomised to standard support with nicotine replacement therapy. <b>Interventions</b> Two interventions were offered in addition to standard support: six weeks' nicotine replacement therapy, provided free, and proactive counselling sessions (repeat telephone calls from, and interaction with, cessation advisors). <b>Main outcome measures</b> The primary outcome was self reported smoking cessation for six or more months after the quit date. The secondary outcome was cessation validated by exhaled carbon monoxide measured at six or more months. <b>Results</b> At six months, 17.7% (n=229) of those offered nicotine replacement therapy reported smoking cessation compared with 20.1% (n=261) not offered such therapy (odds ratio 0.85, 95% confidence interval 0.70 to 1.04), and 18.2% (n=236) offered proactive counselling reported smoking cessation compared with 19.6% (n=254) offered standard support (0.91, 0.75 to 1.11). Data validated by carbon monoxide readings changed the findings for nicotine replacement therapy only, with smoking cessation validated in 6.6% (85/1295) of those offered nicotine replacement therapy compared with 9.4% (122/1296) not offered such therapy (0.67, 0.50 to 0.90). <b>Conclusions</b> Offering free nicotine replacement therapy or additional (proactive) counselling to standard helpline support had no additional effect on smoking cessation. <b>Trial registration</b> ClinicalTrials.gov NCT00775944.
Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study
Authors: M Á Martínez-González, C de la Fuente-Arrillaga, J M Nunez-Cordoba, F J Basterra-Gortari, J J Beunza, Z Vazquez, S Benito, A Tortosa, M Bes-Rastrollo
Journal: BMJ (2008)

To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants.Prospective cohort study with estimates of relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension.Spanish university department.13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years.Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up. Confirmed cases of type 2 diabetes.Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios adjusted for sex and age were 0.41 (95% confidence interval 0.19 to 0.87) for those with moderate adherence (score 3-6) and 0.17 (0.04 to 0.75) for those with the highest adherence (score 7-9) compared with those with low adherence (score <3). In the fully adjusted analyses the results were similar. A two point increase in the score was associated with a 35% relative reduction in the risk of diabetes (incidence rate ratio 0.65, 0.44 to 0.95), with a significant inverse linear trend (P=0.04) in the multivariate analysis.Adherence to a Mediterranean diet is associated with a reduced risk of diabetes.
A case of pemphigus herpetiformis-like atypical pemphigus with IgG anti-desmocollin 3 antibodies
Authors: Y. Nakamura, H. Takahata, K. Teye, N. Ishii, T. Hashimoto, M. Muto
Journal: British Journal of Dermatology (2014)

Journal Article A case of pemphigus herpetiformis‐like atypical pemphigus with IgG anti‐desmocollin 3 antibodies Get access Y. Nakamura, Y. Nakamura Department of Dermatology Yamaguchi University Graduate School of Medicine 1‐1‐1 Minami‐Kogushi Ube 755‐8505 Yamaguchi Japan Search for other works by this author on: Oxford Academic Google Scholar H. Takahata, H. Takahata Department of Dermatology Yamaguchi Red Cross Hospital Yamaguchi Japan Search for other works by this author on: Oxford Academic Google Scholar K. Teye, K. Teye Department of Dermatology Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology Kurume Japan Search for other works by this author on: Oxford Academic Google Scholar N. Ishii, N. Ishii Department of Dermatology Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology Kurume Japan Search for other works by this author on: Oxford Academic Google Scholar T. Hashimoto, T. Hashimoto Department of Dermatology Kurume University School of Medicine and Kurume University Institute of Cutaneous Cell Biology Kurume Japan Search for other works by this author on: Oxford Academic Google Scholar M. Muto M. Muto Department of Dermatology Yamaguchi University Graduate School of Medicine 1‐1‐1 Minami‐Kogushi Ube 755‐8505 Yamaguchi Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 171, Issue 6, 1 December 2014, Pages 1588–1590, https://doi.org/10.1111/bjd.13088 Published: 01 December 2014
Heparan sulfate sulfatase SULF2 regulates PDGFRα signaling and growth in human and mouse malignant glioma
Authors: Joanna J. Phillips, Emmanuelle Huillard, Aaron E. Robinson, Anna Ward, David H. Lum, Mei-Yin Polley, Steven D. Rosen, David H. Rowitch, Zena Werb
Journal: Journal of Clinical Investigation (2012)

Glioblastoma (GBM), a uniformly lethal brain cancer, is characterized by diffuse invasion and abnormal activation of multiple receptor tyrosine kinase (RTK) signaling pathways, presenting a major challenge to effective therapy. The activation of many RTK pathways is regulated by extracellular heparan sulfate proteoglycans (HSPG), suggesting these molecules may be effective targets in the tumor microenvironment. In this study, we demonstrated that the extracellular sulfatase, SULF2, an enzyme that regulates multiple HSPG-dependent RTK signaling pathways, was expressed in primary human GBM tumors and cell lines. Knockdown of SULF2 in human GBM cell lines and generation of gliomas from Sulf2–/– tumorigenic neurospheres resulted in decreased growth in vivo in mice. We found a striking SULF2 dependence in activity of PDGFRα, a major signaling pathway in GBM. Ablation of SULF2 resulted in decreased PDGFRα phosphorylation and decreased downstream MAPK signaling activity. Interestingly, in a survey of SULF2 levels in different subtypes of GBM, the proneural subtype, characterized by aberrations in PDGFRα, demonstrated the strongest SULF2 expression. Therefore, in addition to its potential as an upstream target for therapy of GBM, SULF2 may help identify a subset of GBMs that are more dependent on exogenous growth factor–mediated signaling. Our results suggest the bioavailability of growth factors from the microenvironment is a significant contributor to tumor growth in a major subset of human GBM.
Studies of the expression of the cytochrome P450IA, P450IIB, and P450IIC gene family in extrahepatic and hepatic tissues.
Authors: T Friedberg, P Siegert, M A Grassow, B Bartlomowicz, F Oesch
Journal: Environmental Health Perspectives (1990)

We have studied the expression of three P-450 gene subfamilies in hepatic and extrahepatic tissues using the sensitive RNAse A protection assay. Members of the P450IA subfamily, which encodes the major methylcholanthrene-inducible cytochromes P-450, were found to be not expressed in extrahepatic tissues of untreated animals, raising the question whether these P-450 play a role in the metabolism of carcinogens in unexposed individuals. In contrast, members of the P450IIB family, some of which encode the major phenobarbital-inducible cytochromes P-450, were found to be expressed in some extrahepatic tissues of untreated rats and here most notably in the lung and in sebaceous glands. Members of the P450IIC family, which encode some constitutively expressed cytochromes P-450, were found to be expressed exclusively in the liver.
The Clinical Training of Doctors: An Essay of 1793
Authors: Stephen R. Ell
Journal: JAMA (1981)

Philippe Pinel (1745-1826) is better known for his<i>Treatise on Insanity (1801) and Clinical Medicine</i>(1802). Pinel's career spanned a crucial period in the history of medicine. The education, licensing, and qualification of physicians changed completely in the aftermath of the French Revolution. Elsewhere in Europe, similar changes were taking place. Even more important, Pinel's age saw a fundamental reorientation in concepts of disease. This period in French medicine has been provocatively and controversially discussed in Michel Foucault's<i>La Naissance de la Clinique</i>(translated as<i>The Birth of the Clinic</i>), a book well read in conjunction with this treatise of Pinel. The essay of Pinel published in the present work is one of Pinel's more obscure efforts (it did not win the prize competition in which it was entered). This relative obscurity ought not to conceal its interest, for this is a fascinating discussion of an ideal medical educational system
Health Effects in Fish of Long-Term Exposure to Effluents from Wastewater Treatment Works
Authors: Katherine E. Liney, Josephine A. Hagger, Charles R. Tyler, Michael H. Depledge, Tamara S. Galloway, Susan Jobling
Journal: Environmental Health Perspectives (2005)

Concern has been raised in recent years that exposure to wastewater treatment effluents containing estrogenic chemicals can disrupt the endocrine functioning of riverine fish and cause permanent alterations in the structure and function of the reproductive system. Reproductive disorders may not necessarily arise as a result of estrogenic effects alone, and there is a need for a better understanding of the relative importance of endocrine disruption in relation to other forms of toxicity. Here, the integrated health effects of long-term effluent exposure are reported (reproductive, endocrine, immune, genotoxic, nephrotoxic). Early life-stage roach, Rutilus rutilus, were exposed for 300 days to treated wastewater effluent at concentrations of 0, 15.2, 34.8, and 78.7% (with dechlorinated tap water as diluent). Concentrations of treated effluents that induced feminization of male roach, measured as vitellogenin induction and histological alteration to gonads, also caused statistically significant alterations in kidney development (tubule diameter), modulated immune function (differential cell count, total number of thrombocytes), and caused genotoxic damage (micronucleus induction and single-strand breaks in gill and blood cells). Genotoxic and immunotoxic effects occurred at concentrations of wastewater effluent lower than those required to induce recognizable changes in the structure and function of the reproductive endocrine system. These findings emphasize the need for multiple biological end points in tests that assess the potential health effects of wastewater effluents. They also suggest that for some effluents, genotoxic and immune end points may be more sensitive than estrogenic (endocrine-mediated) end points as indicators of exposure in fish.
Coombs-Positive Hemolytic Anemia Caused by Penicillin Administration
Authors: Lawrence D. Petz, H. Hugh Fudenberg, Eleanor Lloyd
Journal: New England Journal of Medicine (1966)

CIRCULATING antipenicillin antibody (CAPA) was first reported by Ley et al.1 During routine blood-banking procedures the serum of a prospective transfusion recipient was found to agglutinate an entire panel of erythrocytes that had been stored with penicillin as part of the preservative; erythrocytes from the same donors, when not exposed to penicillin, were not agglutinated by this serum. Ley and his co-workers1 and Watson, Joubert and Bennett,2 in tests on 2000 and 3000 unselected serums, respectively, found this antibody only in donors who had previously received penicillin. Although there is an increased incidence of the antibody in allergic persons3 4 5 6 7 8 it . . .
Diet and Respiratory Failure
Authors: Arline G. Olim
Journal: JAMA (1987)

<h3>To the Editor.—</h3> In recent years, a great deal of attention has been paid to the findings that a high-fat, low-carbohydrate diet can help decrease serum carbon dioxide levels in hypercapnic patients<sup>1</sup>and can decrease weaning time for patients who are mechanically ventilated.<sup>2</sup>Pingleton and Harmon,<sup>3</sup>in the conclusion to their article in the June 12 issue of<i>JAMA</i>, "Nutritional Management in Acute Respiratory Failure," stated that a diet consisting of 20% protein, 50% to 60% carbohydrate, and 20% to 30% fat was the ideal mixture of calories for most ventilated patients with respiratory failure. They cited the work of Askanazi.<sup>1</sup>However, Askanazi has shown that diets with 50% of the nonprotein calories as fat emulsion reduce carbon dioxide production and thus the respiratory quotient (RQ). Therefore, the ideal diet consists of 20% protein, 50% to 60% fat, and 20% to 30% carbohydrate, which contradicts the
Judge Kohlsaat Defended.
Authors: Philip Clarkson.
Journal: JAMA (1898)

Chicago, Oct. 31, 1898. <h3>To the Editor:</h3> —Your issue of Oct. 8, 1898, contains a letter from Dr. D. H. Galloway in which it is made to appear that Judge Kohlsaat refuses to allow: 1, more than one physician's bill against an estate; and 2, more than two dollars per visit, no matter what the service may have been. Here are a few facts found in the records of the Probate Court, available to the whole world and ready to the hand of the most casual inquirer: Estate of Sarah A. Toohy. Docket 43, p. 274. Claims allowed Nov. 22, 1897: Dr. D. R. Brower $153. Dr. Jas. H. Etheridge $200. Estate of Daniel Butters. Docket 42, p. 230. Claims allowed May 25, 1897: Dr. Frank Billings $100. Dr. R. D. MacArthur $354. Dr. Jos. M. Patton $150. Estate of Jos. T. Torrence. Docket 43, p. 151. Claims allowed Dec. 31,
REPORT CIII. THE HALDANE-SMITH METHOD OF ESTIMATING THE OXYGEN TENSION OF ARTERIAL BLOOD
Authors: W. A. Osborne
Journal: BMJ (1907)

ouAL 1579 determination of a. Thus a specimen which has a true freezing point, -0 61°C., indicating an advanced state of disease, may appear to bave a value a = 0.580 C., a normal value, if the zero has shifted 0.03°C, a by no means unlikely amount in warm weather.
Diazepam or Paraldehyde for Delirium Tremens
Authors: LEWIS W. GRAY
Journal: Annals of Internal Medicine (1975)

Comments and CorrectionsJune 1, 1975Diazepam or Paraldehyde for Delirium TremensLEWIS W. GRAY, M.D.LEWIS W. GRAY, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-82-6-852_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I take some exception to conclusions from the controlled trial of diazepam and paraldehyde for treatment of delirium tremens recently reported in this journal (Ann Intern Med82:175-180, 1975). A year at Boston City Hospital (BCH) proved to me that the main indication for paraldehyde under the bed was to treat the patient under the bed.I believe the difference in response times for the two drugs lies in the regimen chosen. The average of 150 mg diazepam using 5 mg dose increments compares rather poorly with a mere two or three doses of paraldehyde. That is,...Reference References1. SHARPLESS S: Hypnotics and Sedatives, in The Pharmacological Basis of Therapeutics, edited by GOODMAN LS, GILLMAN A. New York, Macmillan Co., 1970, p. 127 Google Scholar1. LANGBORGSTEDT DH: Rate of pulmonary excretion of paraldehyde in man. Toxicol Appl Pharmacol 15:269-274, 1969 CrossrefMedlineGoogle Scholar2. KLOTZAVANTHOYUMPA UGA: The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55:347-359, 1975 CrossrefMedlineGoogle Scholar3. BLASCHKEMEFFINRICE TPA: Influence of acute viral hepatitis on diphenylhydantoin (DPH) elimination in man. J Clin Invest 53:8, 1974 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 1, 1975Volume 82, Issue 6Page: 852-853KeywordsDiazepamDrugsHepatitis Issue Published: June 1, 1975 PDF downloadLoading ...
The Clinical Value of Tc-99m TRODAT-1 SPECT for Evaluating Disease Severity in Young Patients With Symptomatic and Asymptomatic Wilson Disease
Authors: Ping Wang, Ping Hu, Dian-Chao Yue, Hong Liang, Jie-Hua Xu
Journal: Clinical Nuclear Medicine (2007)

The purpose of this study was to determine the clinical value of applying Tc-99m TRODAT-1 single photon emission computed tomography (SPECT) of the dopamine transporter to evaluate disease severity in young patients with symptomatic or asymptomatic Wilson disease (WD).The evaluation of Tc-99m TRODAT-1 SPECT was performed in 18 patients with symptomatic WD, 13 patients with asymptomatic WD, and, as controls, 12 normal volunteers matched for age and gender. The neurologic symptoms of symptomatic patients were evaluated by an experienced neurologist. The ratios of specific striatal Tc-99m TRODAT-1 binding [with the cerebellum (CB) as the reference region] were calculated as striatum (ST)/CB and compared among the 3 groups. Using correlation analysis, the ratios for the WD patients were compared with clinical data on the severity of neurologic symptoms.Significant differences of ST/CB ratios were found among the 3 groups (Sym vs. Nor, P = 0.000; Asym vs. Nor, P = 0.036; Sym vs. Asym, P = 0.011, respectively). In 23 patients (18 with symptomatic WD, 5 with asymptomatic WD), the posterior putamina showed more remarkable deformation and decreased radiotracer uptake. The ST/CB ratios correlated negatively with the severity of neurologic symptoms (r = -0.80, P < 0.01).The decreased striatal Tc-99m TRODAT-1 uptake found in young WD patients, including symptomatic WD and some asymptomatic WD, as detected with SPECT, seems to indicate presynaptic damage of the dopaminergic nerve terminals. The decrease in radiotracer uptake was more prominent in the posterior putamina than in the caudate heads. The Tc-99m TRODAT-1 SPECT method can be used effectively for evaluating disease severity in WD.
Relationship Between Expression of Hepatitis B Virus Antigens in Isolated Hepatocytes and Autologous Lymphocyte Cytotoxicity in Patients with Chronic Hepatitis B Virus Infection
Authors: Nikolai V. Naumov, Mario Mondelli, Graeme J. M. Alexander, Richard S. Tedder, Adrian L. W. F. Eddleston, Roger Williams
Journal: Hepatology (1984)

Previous studies demonstrated that peripheral blood lymphocytes are cytotoxic to autologous hepatocytes in patients with chronic hepatitis B virus infection. We examined whether cytotoxicity is specifically directed against hepatocytes expressing HBsAg or HBcAg. Viral antigens were detected by immunofluorescence in isolated hepatocytes before and after exposure to T and non-T lymphocytes from 28 patients with chronic HBV infection in an autologous cytotoxicity assay. There was significant reduction in the percentage of HBcAg-positive hepatocytes after exposure to T lymphocytes and, to a lesser extent, after exposure to non-T cells; hepatocytes expressing HBsAg were not affected. Other studies showed that many hepatocytes containing HBcAg have IgG of anti-HBc specificity bound to their nuclei. In the present study, there was significant association between the presence of HBcAg and nuclear IgG in isolated hepatocytes. The ratio between the percentages of HBcAg-positive and IgG-positive hepatocytes (reflecting the proportion of hepatocytes containing free-core antigen) correlated significantly with reduction in HBcAg-positive liver cells after exposure to T cells, but not to non-T cells. These results suggest that hepatocytes in which viral replication is occurring and which express core determinants are susceptible to cell-mediated cytotoxicity and that T-cell cytolysis may be modulated by anti-HBc which is bound to hepatocytes.