tbuckley/cabot-search huggingface dataset:
Abstract 2407: Establishment of a clinically applicable human tyrosine hydroxylase DNA vaccine for anti-neuroblastoma immunotherapy
Authors: Anastasia Shibina, Nicole Nuebener, Diana Seidel, Alexander Stermann, Holger N. Lode, Gerhard Gaedicke
Journal: Cancer Research (2010)

Abstract Background: Neuroblastoma (NB) is an aggressive neoplasm of the sympathetic nervous system in early childhood. Current treatment of high-risk NB consists of intensive myeloablative therapy followed by bone marrow transplantation. However, children with advanced stage disease or those with refractory disease have a poor prognosis. A promising adjuvant approach could be active immunotherapy with DNA vaccines encoding tumor-associated antigens, like tyrosine hydroxylase (TH), which is highly expressed on NB cells. We already established human TH (hTH) DNA vaccination in a syngeneic NB mouse model achieving complete remission of established mass disease and of metastasis. With regard to a clinical application important aspects of this xenogeneic TH DNA vaccination approach have to be readjusted for the use in humans. Methods: For this purpose, hTHcDNA fused to mutated ubiquitin (Gly76[[Unsupported Character - [[Unsupported Character - &amp;#61664;]]]]Ala76) was cloned into the FDA-approved, kanamycin encoding DNA plasmid pING. To examine the functionality of the new plasmid design, pING-hTH was transfected into HEK293 cells. Gene expression was verified by immunofluorescence and western-blot analysis. Furthermore, efficacy of the vaccine was tested in a syngeneic NB mouse model in a prophylactic setting employing attenuated Salmonella typhimurium SL7207 as DNA delivery system. Primary tumors were induced by s.c. injection of NXS2 NB cells and tumor growth was monitored over time. Furthermore, immunological mechanisms of tumor protection were evaluated. Results: In vitro, functional hTH protein expression by the new plasmid design could be established in HEK293 cells. In vivo, xenogeneic TH DNA vaccination induced an anti-NB effect in mice receiving pING-hTH as indicated by a 48-52% reduction in s.c. tumor volume in contrast to empty vector controls. Immunization with hTH-pING DNA-vaccine further generated CTL-mediated responses against NXS2 NB cells and an increase in IFN-γ production. Furthermore, CD8+ T-cells presented at higher levels at primary tumor sites in hTH-vaccinated mice compared to controls. Conclusion: The new vaccine design (hTH-pING) effectively induced an anti-NB immune response in vivo indicated by the suppression of s.c. primary tumors, which is mediated by NB-specific CTLs. Our findings open the possibility for developing a clinically applicable vaccination strategy for one of the most challenging childhood tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2407.
1001 INTERIM ANALYSIS FROM TRIC-1 A STUDY OF METFORMIN WITH PEGINTERFERON ALFA-2A AND RIBAVIRIN IN TREATMENT NAIVE GENOTYPE 1 CHRONIC HEPATITIS C WITH INSULIN RESISTANCE
Authors: M. Romero-Gomez, M. Diago, R.J. Andrade, J.L. Calleja, J. Salmeron, C.M. Fernandez-Rodriguez, R. Sola, J.M. Herrerias, J. Garcia-Samaniego, R. Moreno-Otero, A. Olveira, O. Nuñez, M. De la Mata, F. Jorquera, R.M. Morillas, B. Dalmau, R. Martin-Vivaldi, J.I. Arenas-Ruiz
Journal: Journal of Hepatology (2008)
High prevalence of sleep disturbance in cirrhosis
Authors: Juan Córdoba, Juan Cabrera, Louis Lataif, Plamen Penev, Phyllis Zee, Andrés T. Blei
Journal: Hepatology (1998)

Sleep disturbance is a classic sign of hepatic encephalopathy. However, there are limited data regarding its prevalence in cirrhotic patients without overt hepatic encephalopathy. We assessed the characteristics of sleep in cirrhosis using a sleep questionnaire (n = 44) and actigraphy (n = 20). The results were compared with those of subjects with chronic renal failure and those of healthy controls. Presence of subclinical hepatic encephalopathy, chronotypology profile, and individual’s affective state were also analyzed. The questionnaire indicated an elevated number of cirrhotic patients (47.7%) and patients with chronic renal failure (38.6%) who complained of unsatisfactory sleep compared with healthy controls (4.5%, P &lt; .01). Actigraphy corroborated the deterioration of sleep parameters in cirrhotic patients with unsatisfactory sleep. The sleep disturbance in cirrhosis was not associated with clinical parameters nor with cognitive impairment. Cirrhotic subjects and patients with chronic renal failure with unsatisfactory sleep showed higher scores for depression and anxiety, raising the possibility that the effects of chronic disease may underlie the pathogenesis of sleep disturbance. However, in contrast to chronic renal failure, unsatisfactory sleep in cirrhosis was associated with delayed bedtime, delayed wake-up time, and evening chronotypology. In conclusion, a sleep disturbance is frequent in cirrhotic patients without hepatic encephalopathy and may be related to abnormalities of the circadian timekeeping system.
Angiotensin II Partly Mediates Mechanical Stress–Induced Cardiac Hypertrophy
Authors: Tsutomu Yamazaki, Issei Komuro, Sumiyo Kudoh, Yunzeng Zou, Ichiro Shiojima, Takehiko Mizuno, Hiroyuki Takano, Yukio Hiroi, Kohjiro Ueki, Kazuyuki Tobe, Takashi Kadowaki, Ryozo Nagai, Yoshio Yazaki
Journal: Circulation Research (1995)

Abstract We have previously shown that mechanical stress induces activation of protein kinases and increases in specific gene expression and protein synthesis in cardiac myocytes, all of which are similar to those evoked by humoral factors such as growth factors and hormones. Many lines of evidence have suggested that angiotensin II (Ang II) plays a vital role in cardiac hypertrophy, and it has been reported that secretion of Ang II from cultured cardiac myocytes was induced by mechanical stretch. To examine the role of Ang II in mechanical stress–induced cardiac hypertrophy, we stretched neonatal rat cardiac myocytes in the absence or presence of the Ang II receptor antagonists saralasin (an antagonist of both type 1 and type 2 receptors), CV-11974 (a type 1 receptor–specific antagonist), and PD123319 (a type 2 receptor–specific antagonist). Stretching cardiac myocytes by 20% using deformable silicone dishes rapidly increased the activities of mitogen-activated protein (MAP) kinase kinase activators and MAP kinases. Both saralasin and CV-11974 partially inhibited the stretch-induced increases in the activities of both kinases, whereas PD123319 showed no inhibitory effects. Stretching cardiac myocytes increased amino acid incorporation, which was also inhibited by approximately 70% with the pretreatment by saralasin or CV-11974. When the culture medium conditioned by stretching cardiocytes was transferred to nonstretched cardiac myocytes, the increase in MAP kinase activity was observed, and this increase was completely suppressed by saralasin or CV-11974. These results suggest that Ang II plays an important role in mechanical stress–induced cardiac hypertrophy and that there are also other (possibly nonsecretory) factors to induce hypertrophic responses.
Follow up of blood donors positive for antibodies to hepatitis C virus
Authors: K E Ryan, S MacLennan, J A J Barbara, P E Hewitt
Journal: BMJ (1994)

The hepatitis C virus has been identified as the main cause of post- transfusion hepatitis.1 Mandatory screening of blood donations for antibodies to hepatitis C virus was introduced by the National Blood Transfusion Service on 1 September 1991. Donors confirmed to be positive for antibodies to hepatitis C virus at the North London Blood Transfusion Centre are offered counselling by medical staff at the centre, who explain the relevance of the test results. They are then referred to their general practitioner.

Current evidence suggests that many of the asymptomatic donors positive for antibodies to hepatitis C virus are chronic carriers, in whom the virus replicates.2 Probably some asymptomatic donors will progress to clinically significant, and possibly severe, liver disease in the future. Follow up of the donor by the general practitioner or hospital clinic, or both, will be influenced by information and advice given as a result of the initial counselling. To date there has been no information on the …
Nuclear magnetic resonance studies of forearm muscle in Duchenne dystrophy.
Authors: R J Newman, P J Bore, L Chan, D G Gadian, P Styles, D Taylor, G K Radda
Journal: BMJ (1982)

The forearms of six patients with Duchenne dystrophy were examined by the painless and non-invasive technique of high-resolution nuclear magnetic resonance spectroscopy. The phosphorus spectrum was abnormal in that the ratios of phosphocreatine to adenosine triphosphate and to inorganic phosphate were reduced. Absolute quantification under the conditions of this experiment was not possible but it was probable that in dystrophy the concentration of phosphocreatine in muscle was appreciably reduced. A signal in the phosphodiester region of the spectrum was recorded consistently in patients with dystrophy but not in controls. The intracellular pH of the muscle in the dystrophic patients was abnormally alkaline. The clinical application of nuclear magnetic resonance spectroscopy remains to be proved, but it appears to be a promising non-invasive technique for investigating biochemical abnormalities of muscle disease.
Giant actinic porokeratosis of the scalp
Authors: R.U. Sidwell, J.-E. Seet, N. Francis, C.B. Bunker
Journal: British Journal of Dermatology (2003)

A 70-year-old man presented with three asymptomatic gradually enlarging annular lesions on the scalp, the largest having appeared 7 years previously.There was no family history of similar lesions.He had become bald
Measurement of some potentially hazardous materials in the atmosphere of rubber factories.
Authors: A Nutt
Journal: Environmental Health Perspectives (1976)

Two separate topics of work are outlined: methods for the measurement of chlorinated monomers in PVC and polychloroprene, and also methods for the measurement of these materials in factory air. Typical results which have been obtained in supplies of raw materials, in finished products, and in the working atmosphere at manufacturing operations are given. The second topic concerns the measurement of benzo[a]pyrene in the atmosphere of a tire manufacturing plant. This material is present in trace quantities in the mineral oils and carbon blacks used by the industry. The atmospheric concentrations present at various processes in this plant were measured on a daily basis over a period of two years, and the results obtained compared with results taken concurrently from an outside air station. It is shown that no significant quantities of benzo[a]pyrene are produced by tire manufacturing operations.
Coexistence of Pemphigus Herpetiformis With IgG Antibodies to Desmocollin 1 and Pemphigoid With IgG Antibodies to BP180 C-Terminal Domain and Laminin γ2
Authors: Chika Ohata, Yuko Higashi, Jun Yamagami, Hiroshi Koga, Norito Ishii, Takuro Kanekura, Minao Furumura, Takashi Hashimoto
Journal: JAMA Dermatology (2013)

Pemphigus herpetiformis (PH) cases with IgG antibodies to desmocollin 1 (Dsc1) and pemphigoid cases without mucosal involvement reactive with epitopes on various antigens of mucous membrane pemphigoid (MMP) are rare.1-3 We report a case of coexistence of these 2 bullous diseases.
A SURVEY OF FUNGOUS INFECTION IN THE CAMBRIDGE AREA 1948–1955.
Authors: C. HOWARD WHITTLE
Journal: British Journal of Dermatology (1956)

Journal Article A SURVEY OF FUNGOUS INFECTION IN THE CAMBRIDGE AREA 1948–1955. Get access C. HOWARD WHITTLE, M.D., F.R.C.P. C. HOWARD WHITTLE, M.D., F.R.C.P. United Cambridge Hospitals and University of Cambridge Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 68, Issue 1, 1 January 1956, Pages 1–10, https://doi.org/10.1111/j.1365-2133.1956.tb12749.x Published: 01 January 1956
The Cunning Man
Authors: Alex Paton
Journal: BMJ (2007)

“Should I have taken the false teeth?” Thus, the curt opening of The Cunning Man by Robertson Davies, typical of Canada's foremost man of letters, professor of English, and author of three brilliant trilogies telling stories about the odd ways in which people behave. The speaker is Dr Jonathan Hullah, Toronto physician and sometime police surgeon, whose reminiscences are prompted by the sudden death of his old friend, the saintly Father Ninian Hobbes, while celebrating Good Friday mass at St Aidan's church. The question will be answered only after 400-odd pages …
Concurrent IMRT and weekly cisplatin followed by GDP chemotherapy in newly diagnosed, stage IE to IIE, nasal, extranodal NK/T-Cell lymphoma
Authors: Q-H Ke, S-Q Zhou, W Du, G Liang, Y Lei, F Luo
Journal: Blood Cancer Journal (2014)

On the basis of the benefits of frontline radiation in early-stage, extranodal natural killer (NK)/T-cell lymphoma (ENKTL), we conducted the trial of concurrent chemoradiotherapy (CCRT) followed by three cycles of gemcitabine, dexamethasone and cisplatin (GDP). Thirty-two patients with newly diagnosed, stage IE to IIE, nasal ENKTL received CCRT (that is, all patients received intensity-modulated radiotherapy 56 Gy and cisplatin 30 mg/m2 weekly, 3–5 weeks). Three cycles of GDP (gemcitabine 1000 mg/m2 intravenously (i.v.) on days 1 and 8, dexamethasone 40 mg orally on days 1–4 and cisplatin 75 mg/m2 i.v. on day 1 (GDP), every 21 days as an outpatient were scheduled after CCRT. All patients completed CCRT, which resulted in 100% response that included 24 complete responses (CRs) and eight partial responses. The CR rate after CCRT was 75.0% (that is, 24 of 32 responses). Twenty-eight of the 32 patients completed the planned three cycles of GDP, whereas four patients did not because they withdrew (n=1) or because they had an infection (n=3). The overall response rate and the CR rate were 90.6% (that is, 29 of 32 responses) and 84.4% (that is, 27 of 32 responses), respectively. Only two patient experienced grade 3 toxicity during CCRT (nausea), whereas 13 of the 30 patients experienced grade 4 neutropenia. The estimated 3-year overall survival and progression-free rates were 87.50% and 84.38%, respectively. In conclusion, CCRT followed by GDP chemotherapy can be a feasible and effective treatment strategy for stage IE to IIE nasal ENKTL.
Trichomoniasis in a Closed Community: 100% Follow-up
Authors: E. E. Keighley
Journal: BMJ (1962)

The scepticism with which gynaecologists and venereo logists regarded the possible effectiveness of an oral trichomonacide was doubtless justified by the unsubstan tiated claims that had been put forward some years ago for a chemical compound which is now happily superseded by metronidazole ( flagyl ). This does, in fact, destroy the parasite in the great majority of cases of trichomonal vaginitis. Where it fails to do so there are several possible explanations. The patient might not have taken the pills at all, or might have taken them irregularly. She might have been reinfected after being cured. The drug might in some cases not have been adequately absorbed from the gastro-intestinal tract ; or, where there was no defect in absorption, the concentration of metronidazole in the blood might have been insufficient to destroy the trichomonads in the depth of the uterine cervical glands in which long standing inflammation had led to decreased vascularity. A final theoretical possibility is that some strains of Trichomonas vaginalis might have a natural or acquired resistance to the drug. I am informed (J. A. McFadzean and S. Squires, private communication) that there is little laboratory evidence of defective absorption and no evidence at all of drug-resistant trichomonads. Presumption of cure after treatment with metronidazole is arrived at after a series of negative reports of microscopical and cultural examinations of specimens taken at intervals throughout the three-months follow-up ; but some patients default long before the end of that time. It was thought that it would be of interest to ascertain the effects of oral metronidazole in a closed community in which all the patients could be kept under observation for as long as was considered desirable, and where the risk of reinfection was negligible. These conditions were found in Her Majesty's Prison, Holloway, where the 102 women who are the subjects of this report were treated. In order to save space I have listed the names of the early investigators of metronidazole only in the bibliography. I differ from those French, German, and Canadian workers who continue to give the drug in the form of vaginal suppositories as well as oral tablets. I have used the latter solely, believing that local treatment with this substance is likely to be no more successful than earlier topical applications, the use of which was followed so often by relapse. An actively trichomonicidal substance applied to the vaginal mucosa can never reach deep-seated foci of infection ; and metronidazole so exhibited can cause local irritation.
XRCC1 Deficiency Sensitizes Human Lung Epithelial Cells to Genotoxicity by Crocidolite Asbestos and Libby Amphibole
Authors: Jodie R. Pietruska, Tatiana Johnston, Anatoly Zhitkovich, Agnes B. Kane
Journal: Environmental Health Perspectives (2010)

Background: Asbestos induces DNA and chromosomal damage, but the DNA repair pathways protecting human cells against its genotoxicity are largely unknown. Polymorphisms in XRCC1 have been associated with altered susceptibility to asbestos-related diseases. However, it is unclear whether oxidative DNA damage repaired by XRCC1 contributes to asbestos-induced chromosomal damage.Objectives: We sought to examine the importance of XRCC1 in protection against genotoxic effects of crocidolite and Libby amphibole asbestos.Methods: We developed a genetic model of XRCC1 deficiency in human lung epithelial H460 cells and evaluated genotoxic responses to carcinogenic fibers (crocidolite asbestos, Libby amphibole) and nongenotoxic materials (wollastonite, titanium dioxide).Results: XRCC1 knockdown sensitized cells to the clastogenic and cytotoxic effects of oxidants [hydrogen peroxide (H2O2), bleomycin] but not to the nonoxidant paclitaxel. XRCC1 knockdown strongly enhanced genotoxicity of amphibole fibers as evidenced by elevated formation of clastogenic micronuclei. Crocidolite induced primarily clastogenic micronuclei, whereas Libby amphibole induced both clastogenic and aneugenic micronuclei. Crocidolite and bleomycin were potent inducers of nuclear buds, which were enhanced by XRCC1 deficiency. Libby amphibole and H2O2 did not induce nuclear buds, irrespective of XRCC1 status. Crocidolite and Libby amphibole similarly activated the p53 pathway.Conclusions: Oxidative DNA damage repaired by XRCC1 (oxidized bases, single-strand breaks) is a major cause of chromosomal breaks induced by crocidolite and Libby amphibole. Nuclear buds are a novel biomarker of genetic damage induced by exposure to crocidolite asbestos, which we suggest are associated with clustered DNA damage. These results provide mechanistic evidence for the epidemiological association between XRCC1 polymorphisms and susceptibility to asbestos-related disease.Editor's SummaryPathways involved in the repair of asbestos-induced DNA damage are largely unknown, but XRCC1 polymorphisms that may influence the efficacy of DNA repair have been associated with susceptibility to asbestos-related diseases. Pietruska et al. (p. 1707) examined the role of XRCC1 in genotoxic effects of crocidolite and Libby amphibole asbestos in normal and XRCC1-deficient human lung epithelial H460 cells. The authors report that oxidative DNA damage, including oxidized bases and single-strand breaks, was increased following asbestos exposure in XRCC1-deficient cells compared with control cells, and was a major cause of chromosomal breaks induced by crocidolite and Libby amphibole. Nuclear buds, a possible marker of clustered DNA damage, were induced by crocidolite asbestos but not Libby amphibole. The authors conclude that their findings provide mechanistic support for epidemiologic evidence linking XRCC1 polymorphisms and susceptibility to asbestos-related disease.
133. Adenovirus-Light Chain Inhibition of Growth Hormone Release from Pituitary Adenoma Cells
Authors: Thais Federici, Qingshan Teng, Mary Garrity-Moses, Christina Krudy, Jun Yang, Nicholas M. Boulis
Journal: Molecular Therapy (2006)

Background: Pituitary tumors are the most common primary intracranial neoplasms. Growth hormone (GH) excess can be caused either by direct GH hypersecretion or GH excess secondary to GH- releasing factor (GHRF) hypersecretion. Neuroendocrine cells release transmitters and neuropeptides by calcium-dependent exocytosis of the contents of vesicles. This process requires assembly of SNARE proteins. Tetanus toxin light chain (TeTxLC) is a 50-kDa protein responsible for blockage of neurotransmitter release through digestion of three SNARE proteins (VAMP/synaptobrevin, syntaxin, and SNAP-25). The present study tested the hypothesis that adenoviral delivery of tetanus toxin light chain (Ad-LC) gene would cause inhibition of exocytotic release of GH. Methods: To study the properties of LC gene expression in pituitary tumors, we used GH3 cells from rat pituitary adenoma (ATCC). Following treatment with adenoviral vectors expressing TeTxLC (Ad-LC), GFP (Ad-GFP) or PBS, supernatants were collected at different time-points. For measurement of GH levels, assays were performed with an ultra-sensitive mouse/rat GH ELISA kit (DSLabs). Results: GH ELISA assay revealed a reduction in GH levels in the Ad-LC-treated groups (90% of reduction 96 hours after treatment), but not in the Ad-GFP and PBS groups. Moreover, TUNEL staining did not detect reduced cell density. Conclusions: This study reveals the ability of our Ad-LC to inhibit GH release. Although most pituitary tumors are considered benign, conventional therapies are often unsatisfactory. With the development of safe and targeted controllable vector systems, gene therapy might become a valuable approach for treating neuroendocrine tumors, such as pituitary adenomas.
Do low-grade and low-volume prostate cancers bear the hallmarks of malignancy?
Authors: Hashim Uddin Ahmed, Manit Arya, Alex Freeman, Mark Emberton
Journal: The Lancet Oncology (2012)

Prostate cancer is generally multifocal and consists of a dominant focus-measured by tumour volume and deemed the index lesion-and one or more separate, secondary tumour foci of smaller volume. Much laboratory and clinical evidence has shown that we need to rethink how we regard low-grade and low-volume prostate lesions. In this Personal View, we discuss why small, low-grade Gleason pattern prostate lesions, which are currently designated as prostate cancer, could be regarded as non-malignant. These lesions either do not meet the criteria of the hallmarks of cancer or robust evidence that they do so is absent, by contrast with large lesions with a high Gleason grade, which seem to cause most metastatic disease.