tbuckley/cabot-search huggingface dataset:
Suppression of Murine Tumor Growth by Immune Reaction to the Bacillus Calmette-Guérin Strain of &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt;
Authors: Gerald L. Bartlett, Berton Zbar, Herbert J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Suppression of Murine Tumor Growth by Immune Reaction to the Bacillus Calmette-Guérin Strain of Mycobacterium bovis Get access Gerald L. Bartlett, Gerald L. Bartlett Biology Branch, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Berton Zbar, Berton Zbar Biology Branch, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert J. Rapp Herbert J. Rapp Biology Branch, National Cancer Institute,2Bethesda, Maryland 20014 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 1, January 1972, Pages 245–257, https://doi.org/10.1093/jnci/48.1.245 Published: 01 January 1972 Article history Received: 30 July 1971 Accepted: 23 September 1971 Published: 01 January 1972
Cytidine deamination and cccDNA degradation: A new approach for curing HBV?
Authors: Siyuan Ding, Michael D. Robek
Journal: Hepatology (2014)

Current antiviral agents can control but not eliminate hepatitis B virus (HBV), because HBV establishes a stable nuclear covalently closed circular DNA (cccDNA). Interferon-α treatment can clear HBV but is limited by systemic side effects. We describe how interferon-α can induce specific degradation of the nuclear viral DNA without hepatotoxicity and propose lymphotoxin-β receptor activation as a therapeutic alternative. Interferon-α and lymphotoxin-β receptor activation up-regulated APOBEC3A and APOBEC3B cytidine deaminases, respectively, in HBV-infected cells, primary hepatocytes, and human liver needle biopsies. HBV core protein mediated the interaction with nuclear cccDNA, resulting in cytidine deamination, apurinic/apyrimidinic site formation, and finally cccDNA degradation that prevented HBV reactivation. Genomic DNA was not affected. Thus, inducing nuclear deaminases—for example, by lymphotoxin-β receptor activation—allows the development of new therapeutics that, in combination with existing antivirals, may cure hepatitis B. (Hepatology 2014;00:000-000)
Absence of BRAF and HRAS mutations in eruptive Spitz naevi
Authors: S. Gantner, T. Wiesner, L. Cerroni, I. Lurkin, E.C. Zwarthoff, M. Landthaler, C. Hafner
Journal: British Journal of Dermatology (2011)

Eruptive Spitz naevi have been reported rarely in the literature. In solitary Spitz naevi, BRAF and HRAS mutations, as well as increased copy numbers of chromosome 11p have been identified.To investigate the genetic changes underlying eruptive Spitz naevi.We report on a 16-year-old boy who developed multiple disseminated eruptive Spitz naevi within a few months. We analysed BRAF, HRAS, KRAS and NRAS genes in 39 naevi from this patient for hotspot mutations. Furthermore, comparative genomic hybridization analysis was performed in three lesions.None of the Spitz naevi displayed a mutation in the analysed genes, and no chromosomal imbalances were observed. Conclusions Our results indicate that the typical genetic alterations described in solitary Spitz naevi appear to be absent in eruptive Spitz naevi. Yet unknown alternative genetic alterations must account for this rare syndrome.
Demonstration of Tumor-Specific Immunity Against Antigens Unrelated to the Mammary Tumor Virus in Spontaneous Mammary Adenocarcinomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Donald L. Morton, George F. Miller, David A. Wood
Journal: JNCI Journal of the National Cancer Institute (1969)

Attempts were made to induce immunity against 11 different mammary adenocarcinomas of recent spontaneous origin in C3H/HeN and DBA/2JN mice congenially infected with the mammary tumor virus (MTV). The temporary growth followed by excision of an isograft of 5 of these neoplasms or pretreatment with irradiated tumor tissue induced a significant degree of immunity against subsequent challenge inoculations with the same tumor. This immunity was manifested in the mice immunized with tumor by a lower incidence of tumor development, a delay in tumor appearance, smaller tumor size, and prolongation of survival time. Normal tissues from the same mouse in which the tumor originated would not induce immunity and were not rejected when transplanted into tumor-immune mice. Immunity appeared to be individually specific against the tumor used for immunization, and extensive cross-immunity against other mammary adenocarcinomas was not observed. This immunity appeared unrelated to the MTV, since pretreatment with normal and neoplastic tissues containing the agent did not induce similar resistance against tumor challenge. Mammary tumors of histologic type A were more frequently immunogenic than those of type B. These data provide evidence that some spontaneous mammary adenocarcinomas contain tumor-specific antigens unrelated to the MTV that are immunogenic in isogenic mice congenially infected and tolerant to the MTV. The demonstration of non-cross-reactive tumor-specific antigens in mammary carcinomas, analogous to the antigens of carcinogen-induced neoplasms, represents a new class of antigens in virus-induced tumors.
Factors Affecting the Extrusion Rates of Ventilation Tubes
Authors: I J Mackenzie
Journal: Journal of the Royal Society of Medicine (1984)

A survey in which 939 ventilation tubes of 8 different patterns were inserted and reviewed (up to a maximum of 2 1/4 years) is analysed. Various factors determining the rate of extrusion are discussed. The Sheehy Collar Button tube remained functional for a longer period than any of the other tubes included in the survey.
Validity of the forced expiratory flow 25-75 for identification of bronchial hyperresponsiveness in a pulmonary function laboratory
Authors: Ramos-Quispe Yolanda, Chancafe-Morgan Jorge, Gomez-García Rosa, Vargas-Espinal Julio, Rojas-Moreno-Tome Rosa María, Puente-Maestú Luis
Journal: European Respiratory Journal (2013)

Objective: To assess the validity of the Forced Expiratory Flow 25-75 (FEF 25-75) for identification of a positive bronchial hyperresponsiveness (BH). Methods: We conducted a prospective, consecutive, observational study. All subjects who underwent a spirometry and methacholine test (MT) for suspicion of BH from January 2009 to November 2010 were included. The cut-off point used for a positive FEF 25-75 was a value <60% (from the theoretical value) and for MT a PC20<=8 mg/ml. We calculated the FEF 25-75 sensitivity (S), specificity (E), positive predictive value (PPV) and negative predictive value (NPV). The data was analyzed by the SPSS 15 statistical program.

Results: A total of 343 subjects were included. The mean age was 41,9 years (SD 15,4) and 103 (30 %) were male. The mean height and BMI were 163,7 cms (SD 9,7) and 26,9 Kg/m2 (SD 5,1) respectively. Of them, 167 (48,7%) had a positive MT and 66 (19,2%) a positive FEF 25-75 result. We found a strong association between FEF 25-75 and MT (X2, p<0,000). The S, E, PPV and NPV were 29,3%, 90,3%, 74,2% and 57,4% respectively.

Conclusions: According to our data, there is a strong association between FEF 25-75 and MT. The FEF 25-75 seems to have a high E and PPV for identification of bronchial hyperresponsiveness. The FEF 25-75 might be useful to gauge the MT initial dose.
Stable isotope labelled amino acid culturing: A novel approach to identify pathways involved in MIF signalling
Authors: Kirsty Russell, Kate Heesom, Simon Hall, Sebastian Johnston, Peter Barnes, Ian Adcock
Journal: European Respiratory Journal (2013)

Chronic obstructive pulmonary disease (COPD) shows poor clinical improvement with steroids. Macrophage Migration Inhibitory Factor (MIF) counter-regulates steroid action although the mechanism is unknown. Stable isotope labelled amino acid cell culture (SILAC) involves incorporating differently labelled amino acids into cells to allow comparison of protein profiles. SILAC was used to investigate the effect of MIF on intracellular signalling pathways.  THP-1 cells were grown in SILAC media and then stimulated with or without MIF for 24 hours, the cells were lysed and proteins extracted. Incorporation of the labelled amino acids were measured and analysed by LC-MSMS. Pathways identified were validated by qRT-PCR, ELISA and Western blotting.  MIF treatment up-regulated 70 and down-regulated 163 proteins; pathway analysis identified the RIG-I-like receptor (RLR) pathway. In THP-1 cells, as the main MIF target, MIF was induced by Poly I:C in a concentration-dependent manner and RV16 infection induced  MIF  expression in a time-dependent manner. BAL macrophage proteins were analysed at baseline and 7 days post RV16 infection in non-smokers, smokers and COPD patients. Smokers and COPD patients showed a significant decrease in intracellular MIF post-infection.  We used proteomics to define a novel mechanism of MIF action in THP-1 cells and translated this to primary human cells. Viral activation induced MIF release from THP-1 cells and was associated with a loss of intracellular MIF in BAL macrophages 7 days post infection in smokers and COPD patients. This proteomics approach has the ability to define novel mechanisms for understanding drug or disease effects.
Melanoma and naevi with a globular pattern: confocal microscopy as an aid for diagnostic differentiation
Authors: E. Benati, G. Argenziano, A. Kyrgidis, E. Moscarella, S. Ciardo, S. Bassoli, F. Farnetani, S. Piana, A.M. Cesinaro, A. Lallas, S. Borsari, G. Pellacani, C. Longo
Journal: British Journal of Dermatology (2015)

Dermoscopically, one of the most common findings in melanocytic lesions is a globular pattern. A regular globular pattern is a common finding in naevi. Melanoma can also show a globular pattern, with globules typically irregular in size, colour and distribution.To investigate the likelihood of diagnosing melanoma according to distinct dermoscopic and confocal aspects.Dermoscopic and confocal aspects of 83 excised melanocytic lesions dermoscopically showing globules were analysed.Our study population included 39 acquired melanocytic naevi, 16 Spitz naevi and 28 melanomas. Univariate analysis showed that regular distribution of globules on dermoscopy is associated with a ninefold lower risk for melanoma, whereas an irregular distribution is associated with an almost 10-fold increased risk for melanoma. Concerning confocal features, dense nests are associated with a fivefold lower risk for melanoma, whereas loosely arranged nests are associated with an almost sixfold risk for melanoma; moreover, the presence of round cells is associated with a 17-fold lower risk for melanoma, whereas pleomorphic cells are associated with an almost 16-fold risk for melanoma.So that melanoma is not missed, clinicians should carefully analyse globular lesions in adults, focusing, in particular, on the distribution of globules and on the presence of confocal cytological atypia.
Elution of Tumor-Directed Antibody From Kidneys of Mammary Tumor-Bearing Mice2
Authors: Susan F. Siovin, Sidney J. Bennett, Robert R. Pascal
Journal: JNCI Journal of the National Cancer Institute (1977)

Immunoglobulin-containing eluates, prepared from kidneys of Paris Rill mammary tumor-bearing mice approximately 10 months old, were incubated with frozen sections of mouse mammary tumor and normal lactating mammary gland and examined by immunofluorescence. The eluates diffusely stained the tumor but did not stain the nonneoplastic lactating mammary gland. Mammary tumor and normal lactating mammary gland were both stained by an antiserum to mammary tumor virus (MuMTV). The euglobulin portion of the eluates, when fractionated on a Sephadex G-200 column, yielded an IgG fraction which was shown by immunodiffusion to react with Paris Rill mammary tumor extract and with anti-mouse globulin but not with nonneoplastic mouse tissue extracts. Since the lactating mammary glands of these animals contain MuMTV, the antibody-containing fraction eluted from the kidneys appeared to be tumor directed rather than virus directed.
Phase II Trial of Doxorubicin and Paclitaxel Plus Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer: An Eastern Cooperative Oncology Group Study
Authors: Joseph A. Sparano, Ping Hu, Radha M. Rao, Carla I. Falkson, Antonio C. Wolff, William C. Wood
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Several groups have reported that the combination of doxorubicin plus paclitaxel given as a 3-hour intravenous (IV) infusion for up to eight cycles produces a high response rate (&gt; 80%) and complete response rate (&gt; 20%) in metastatic breast cancer, but is also complicated by a 20% incidence of congestive heart failure (CHF). The purpose of this phase II trial was to evaluate the antineoplastic activity of the regimen in a multi-institutional setting and to reduce the incidence of cardiotoxicity by limiting treatment to a maximum of six cycles. PATIENTS AND METHODS: Fifty-two patients with advanced breast cancer received doxorubicin (60 mg/m 2 by IV injection) followed 15 minutes later by paclitaxel (200 mg/m 2 by IV infusion over 3 hours) every 3 weeks for four to six cycles. RESULTS: Objective responses occurred in 25 of 48 assessable patients (52%; 95% confidence interval [CI], 38% to 66%), including four complete responses (8%; 95% CI, 0% to 16%). The median cumulative doxorubicin dose given was 240 mg/m 2 (range, 132 to 360 mg/m 2 ). Eleven patients (21%) were documented as having a decrease in the LVEF below normal, including three patients (6%; 95% CI, 0% to 12%) who developed CHF. CONCLUSION: The doxorubicin/paclitaxel regimen that we used is unlikely to produce an objective response rate of more than 70% and a complete response rate of more than 20% in patients with metastatic breast cancer, and proved to be excessively cardiotoxic for use in the adjuvant setting.
Effects of high ambient ozone on lung function, nasal flow and exhaled NO
Authors: Lazaros Sichletidis, Dionisios Spyratos, Diamantis Chloros, D. Melas, A. Bais
Journal: European Respiratory Journal (2013)

Background: Clinical studies have shown that ozone (O3) exposure exacerbates respiratory symptoms. The aim of the present study was to investigate the relationship between elevated atmospheric ozone concentrations and lung function parameters, nasal airflow and exhaled NO before and 2 hours after brisk walking.

Methods: Thirty non-smokers volunteers (33.6±12 year old) with no history of respiratory/allergy diseases underwent spirometry, rhinomanometry and FeNO measurement (Niox Mino, Aerocrine) before and 2 hours after brisk walking during two separate days in Panorama (altitude 330m), Thessaloniki, Greece ; one with low (March 2012, visit 2) and one with high (June 2011, visit 1) ozone level. We compared differences (post-pre walking %) for all measurements.

Results: Concentration of ozone was: 197 μg/m3 (average hourly value) and 90 μg/m3 for the two days. As it is shown in table 1, % differences were similar for all parameters.

View this table:

Table 1. Comparison of differences (post-pre walking) for all measured parameters between the two visits





Conclusion: We found that acute exposure to ambient ozone levels above permissible limits had no significant effects on lung function, nasal airflow and exhaled NO.
The Western Washington Intravenous Streptokinase in Acute Myocardial Infarction Randomized Trial.
Authors: J W Kennedy, G V Martin, K B Davis, C Maynard, M Stadius, F H Sheehan, J L Ritchie
Journal: Circulation (1988)

Three hundred sixty-eight patients were randomly assigned to receive intravenous streptokinase (IVSK) (n = 191) or standard therapy (n = 177) to determine the efficacy of IVSK in the treatment of acute myocardial infarction. The mean time to treatment was 3.5 hr. At 14 days there were 12 deaths in the treatment group (6.3%) and 17 deaths in the control group (9.6%) (p = .23). Early mortality was related to infarct location. Fourteen day mortality for anterior infarctions was 10.4% for treatment with IVSK and 22.4% for control patients (p = .06) and was similar for IVSK-treated patients with inferior infarctions, 4.0% vs 1.8% (p = .32). For those randomized under 3 hr, 14 day mortality tends to be lower in treated patients, 5.2% vs 11.5% (p = .11). There was significant improvement in long-term survival for patients with anterior infarction; 2 year survival was 81% for IVSK-treated patients and 65% for control patients (p = .05). There was no improvement in survival for patients with inferior myocardial infarction (p = .27). We conclude that patients with anterior myocardial infarction have improved survival when treated within the first 6 hr of symptoms. Patients with inferior infarction do not appear to have improved survival with thrombolytic therapy. Some of this improvement in survival in patients with anterior infarction may be due to a higher frequency of revascularization procedures in the treatment group.
The Safety of Long-Acting β-Agonists among Patients with Asthma Using Inhaled Corticosteroids
Authors: Roman Jaeschke, Paul M. O'Byrne, Filip Mejza, Parameswaran Nair, Wiktoria Leśniak, Jan Brożek, Lehana Thabane, Ji Cheng, Holger J. Schünemann, Malcolm R. Sears, Gordon Guyatt
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: Inhaled long-acting β-agonists (LABAs), when used as monotherapy in asthma, may increase asthma-related hospitalizations, life threatening events requiring intubation/mechanical ventilation, and asthma-related deaths, but concomitant use of inhaled corticosteroids (ICS) may modify this effect.Objectives: To determine the safety of long-acting β-agonists among patients with asthma using corticosteroids.Methods: We conducted a systematic review and metaanalysis of parallel-group, blinded, randomized, controlled trials with at least 12 weeks of treatment addressing the impact of LABA on asthma-related and total morbidity and mortality in patients concomitantly using ICS. We searched MEDLINE, EMBASE, ACPJC, and Cochrane (Central) databases, and contacted authors and sponsors.Measurements and Main Results: We used a random effects model to pool results from different studies as odds ratios (ORs) (95% confidence interval [CI]) (OR < 1.0 favors LABA). The search yielded 62 relevant studies included in this analysis. Among over 29,000 participants (15,710 taking LABA, with over 8,000 patient-years observed in the LABA groups), there were three asthma-related deaths and two asthma-related, nonfatal intubations (all in LABA groups; ≤ one event per study). Differences in asthma-related hospitalizations (OR, 0.74; 95% CI, 0.53–1.03) and asthma-related serious adverse events (mostly hospitalizations; OR, 0.75; 95% CI, 0.54–1.03) failed to reach statistical significance. The OR for total mortality was 1.26 (95% CI, 0.58–2.74), reflecting 14 deaths in LABA groups and eight deaths in control groups, respectively.Conclusions: In patients with asthma using ICS, LABA did not increase the risk of asthma-related hospitalizations. There were very few asthma-related deaths and intubations, and events were too infrequent to establish LABA's relative effect on these outcomes.
Studies on the Mode of Action of Cholera Toxin
Authors: Barbara Beckman, Jorge Flores, Patricia A. Witkum, Geoffrey W. G. Sharp
Journal: Journal of Clinical Investigation (1974)

To gain further insight into the mechanism of action of cholera toxin, solubilized preparations of adenylate cyclase from control and toxin-treated rat livers were studied. Adenylate cyclase activity was measured in both particulate and solubilized form in rat liver under control conditions and after intravenous injection of cholera toxin. Cholera toxin caused a 3.3-fold activation of adenylate cyclase in the particulate preparation and a 5.8-fold increase in the solubilized preparation. Thus, the ability of cholera toxin to stimulate adenylate cyclase is present even when the enzyme membrane environment is disrupted. Furthermore, the solubilized enzyme, after treatment with cholera toxin, retained its ability to respond to catecholamines, but not to glucagon. In contrast, the control enzyme lost its responsiveness to catecholamines and glucagon after solubilization.
Duration of Chemotherapy in Advanced Non–Small-Cell Lung Cancer: A Randomized Trial of Three Versus Six Courses of Mitomycin, Vinblastine, and Cisplatin
Authors: Ian E. Smith, Mary E.R. O’Brien, Denis C. Talbot, Marianne C. Nicolson, Janine L. Mansi, Tamas F. Hickish, Alison Norton, Susan Ashley
Journal: Journal of Clinical Oncology (2001)

PURPOSE: So far there are no published data on optimal duration of chemotherapy for advanced non–small-cell lung cancer (NSCLC); six or more courses are usually recommended. We have carried out a multicenter randomized trial comparing three versus six courses of chemotherapy. PATIENTS AND METHODS: Patients with stage IIIb or IV NSCLC were randomized at start of treatment to receive either three or six courses of mitomycin 8 mg/m 2 (courses 1, 2, 4, and 6), vinblastine 6 mg/m 2 , and cisplatin 50 mg/m 2 (MVP) every 21 days. Treatment was stopped early in both arms for progressive disease or unacceptable toxicity. Key end points were overall survival, duration of symptom relief, and quality-of-life assessment using the European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 with lung cancer–specific module QLQ-LC13. RESULTS: Three hundred eight patients were randomized. Seventy-two percent of the 155 patients randomized to three courses completed treatment. In the 153 patients randomized to six courses, 73% completed three courses and 31% six courses. Median survival was 6 versus 7 months, respectively, and 1-year survival 22% versus 25% (P = .2). Median duration of symptom relief was 4.5 months (both arms), and 8% versus 18% had continuing symptom relief (P = .4). Quality-of-life parameters were the same or improved for patients randomized to only three courses, including significantly decreased fatigue (P = .03) and a trend toward decreased nausea and vomiting (P = .06). CONCLUSION: Our findings show no evidence for additional clinical benefit by continuing MVP chemotherapy beyond three courses. This challenges current orthodoxy of six courses or more. Further trials addressing duration of chemotherapy are now warranted, particularly with newer chemotherapy schedules.