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Extensive deep vein thrombosis as a complication of testicular cancer treated with the BEP protocol (bleomycin, etoposide and cisplatin): case report / Trombose venosa profunda extensa como complicação de um tumor do testículo tratado com o protocolo BEP (cisplatina, bleomicina e etoposide): relato de caso  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese CONTEXTO: Não há relatos na literatura de trombose venosa profunda (TVP) extensa associada ao protocolo de quimioterapia cisplatina, bleomicina e etoposite (BEP). RELATO DO CASO: O paciente era um adolescente de 18 anos com um tumor germinativo não-seminomatoso no testículo direito, com metástases p [...] ulmonares, hepáticas e retroperitoneais. Após orquiectomia radical, o paciente começou a receber quimioterapia de acordo com o protocolo BEP (sem profilaxia rotineira para TVP). No quarto dia do ciclo, TVP massiva foi diagnosticada, estendendo-se das veias poplíteas até o segmento inferior da veia cava torácica. Tratamento trombolítico foi iniciado imediatamente com estreptoquinase. No segundo dia da terapia trombolítica, o paciente desenvolveu insuficiência renal aguda, devido ao acometimento das veias renais pela trombose. Estroptoquinase foi mantida por seis dias e o paciente teve evolução surpreendentemente favorável. Abstract in english CONTEXT: There are no reports in the literature of massive deep venous thrombosis (DVT) associated with cisplatin, bleomycin and etoposide (BEP) cancer treatment. CASE REPORT: The patient was a 18-year-old adolescent with a nonseminomatous germ cell tumor of the right testicle, with the presence of [...] pulmonary, liver, and massive retroperitoneal metastases. Following radical orchiectomy, the patient started chemotherapy according to the BEP protocol (without routine prophylaxis for DVT). On day 4 of the first cycle, massive DVT was diagnosed, extending from both popliteal veins up to the thoracic segment of the inferior vena cava. Thrombolytic therapy with streptokinase was immediately started. On day 2 of thrombolytic therapy, the patient developed acute renal failure, due to extension of the thrombosis to the renal veins. Streptokinase was continued for six days and the outcome was remarkably favorable.

Mano, Max Senna; Guimarães, José Luiz Miranda; Sutmöller, Sören Franz Marian Chicata; Reiriz, André Borba; Sutmöller, Christian Sandor Svend Chicata; Di Leo, Angelo.

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Bleomycin-induced pulmonary fibrosis after tumor lysis syndrome in a case of advanced yolk sac tumor treated with bleomycin, etoposide and cisplatin (BEP) chemotherapy.  

Science.gov (United States)

Ovarian yolk sac tumor (YST) is a highly aggressive malignancy arising in young women. Chemotherapy has dramatically improved the prognosis, and bleomycin, etoposide, and cisplatin (BEP) combination chemotherapy appears to be the most effective combination regimen. A 23-year-old woman was admitted to our hospital with worsening abdominal distention and a lower abdominal mass. She was diagnosed with a stage IIIc pure YST of the right ovary, and right salpingo-oophorectomy was performed; there were numerous disseminated peritoneal tumors within the abdominal cavity. A few days postoperatively, massive ascites developed, and right hydronephrosis occurred. Chemotherapy with BEP was started, and after 24 h of administration, oliguria and tumor lysis syndrome (TLS) developed. Continuous hemodiafiltration was started, and hemodialysis was initiated following full-dose standard cisplatin and etoposide on days 2-5 of the 1st cycle. After the electrolyte abnormalities and the elevation of creatinine became normal, the patient received an additional three cycles of BEP and achieved complete remission. However, she also suffered from severe non-hematological toxicities, including grade 3 left ventricular dysfunction and grade 4 pulmonary fibrosis. In the case of rapidly progressing and high-volume YST treated with BEP chemotherapy, special attention should be paid to bleomycin-induced pulmonary toxicity following TLS. Further study is required to optimize drug exposure to ensure efficacy and reduce the risk of side effects in this population. PMID:22127348

Doi, Mihoko; Okamoto, Yohei; Yamauchi, Masami; Naitou, Hiroyuki; Shinozaki, Katsunori

2012-10-01

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Paclitaxel, bleomycin, etoposide, and cisplatin (T-BEP) as initial treatment in patients with poor-prognosis germ cell tumors (GCT): a phase II study.  

Science.gov (United States)

First line treatment of patients pts with poor-prognosis GCT, using BEP, is unsatisfactory. T-BEP (paclitaxel followed by BEP) demonstrated promising efficacy in the group of pts with intermediate and poor prognosis GCT. We present the results achieved with 1st line T-BEP in pts with poor-prognosis CGT. Twenty-four pts received T-BEP as initial therapy. Three pts (12.5%) had primary mediastinal GCT. Four cycles of T-BEP were given 21 days apart. Paclitaxel 175 mg/m2 was administered on day 1 before administration of BEP. The administration of G-CSF was not scheduled. Surgical resection of all radiographic residua was considered. All pts were assessable for response. Complete or partial response with negative tumor markers was achieved in 13 pts (54.2%; CI 95%: 34.3-74.1%). Median follow-up is 35.6 months. Median survival was not achieved and median time-to-progression is 9.5 months. Myelosuppression was the major toxicity with Gr3-4 granulocytopenia experienced in 52.1% of all courses. There were two treatment-related deaths due to sepsis. Patients treated with 1st line T-BEP didn't achieve higher response rate or time to progression. However, the overall survival observed in our study is surprisingly long. We do not recommend using this regimen without G-CSF support due to substantial toxicity. PMID:17447857

Mardiak, J; Sálek, T; Sycová-Milá, Z; Obertová, J; Recková, M; Mego, M; Hlavatá, Z; Brozmanová, K; Risnyovzská, Z; Svetlovská, D; Koza, I

2007-01-01

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Beamed-Energy Propulsion (BEP) Study  

Science.gov (United States)

The scope of this study was to (1) review and analyze the state-of-art in beamed-energy propulsion (BEP) by identifying potential game-changing applications, (2) formulate a roadmap of technology development, and (3) identify key near-term technology demonstrations to rapidly advance elements of BEP technology to Technology Readiness Level (TRL) 6. The two major areas of interest were launching payloads and space propulsion. More generally, the study was requested and structured to address basic mission feasibility. The attraction of beamed-energy propulsion (BEP) is the potential for high specific impulse while removing the power-generation mass. The rapid advancements in high-energy beamed-power systems and optics over the past 20 years warranted a fresh look at the technology. For launching payloads, the study concluded that using BEP to propel vehicles into space is technically feasible if a commitment to develop new technologies and large investments can be made over long periods of time. From a commercial competitive standpoint, if an advantage of beamed energy for Earth-to-orbit (ETO) is to be found, it will rest with smaller, frequently launched payloads. For space propulsion, the study concluded that using beamed energy to propel vehicles from low Earth orbit to geosynchronous Earth orbit (LEO-GEO) and into deep space is definitely feasible and showed distinct advantages and greater potential over current propulsion technologies. However, this conclusion also assumes that upfront infrastructure investments and commitments to critical technologies will be made over long periods of time. The chief issue, similar to that for payloads, is high infrastructure costs.

George, Patrick; Beach, Raymond

2012-01-01

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Energy consumption in commerical buildings: a comparison with BEPS budgets  

Energy Technology Data Exchange (ETDEWEB)

Metered energy consumption data have been collected on existing commercial buildings to help establish the proposed Building Energy Performance Standards (BEPS). The search has identified 84 buildings whose metered energy consumption is equal to or less than that proposed for their BEPS budgets and another 7 buildings whose metered consumption is less than 20% above their BEPS budgets. The methodology used to identify the buildings and to collect their metered energy consumption data are described. The data are analyzed and summarized and conclusions are drawn.

None

1980-09-22

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DOE to ease weighting of fuels in BEPS plan  

Energy Technology Data Exchange (ETDEWEB)

The portion of DOE's proposed Building Efficiency Performance Standards (BEPS) which deals with fuel-weighting factors may be eased to consider regional rather than national fuel prices and fuel mixes as a result of criticism expressed at hearings. Critics of the BEPS plan object to the penalties on regions where fossil fuels are used to generate electricity. They question the concept of using weighting factors to influence the mix of fuels used in new buildings. Speakers at the BEPS hearing claimed it will burden the hotel industry by eliminating construction of moderately priced facilities, criticized the statistical base used for the standards, suggested the weighting factors may be counterproductive to national goals, and expressed concern that the complex rules will be difficult to implement. (DCK)

Murnane, T.

1980-04-28

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Pockets of opportunity: multicultural marketing strategies for BEP growth.  

Science.gov (United States)

Ranked among the 50 largest food service corporations in America, the Randolph-Sheppard Business Enterprise Program (BEP) represents a challenging and rewarding career opportunity for Americans who are legally blind. In recent years, however, the number of facilities and facility managers has declined. Multicultural consumers represent a major emerging growth market. The multicultural market is one of the most overlooked retail markets in the United States--and the one with the most buying power and growth potential. Multicultural marketing is among the least understood strategies available to facility managers, vocational rehabilitation counselors and BEP directors. Four major minority markets are discussed and marketing strategies are offered to help BEPs target and serve these unique consumers. PMID:12897395

Schaefer, Kelly

2003-01-01

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Modulation of bleomycin cytotoxicity.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Lethal effects of a 75-microgram/ml concentration (approximately 5 X 10-5 M) of bleomycin on stationary-phase haploid or diploid cells of the eucaryote Saccharomyces cerevisiae were negated in the presence of 0.05 M phosphate buffer (pH 7). High cell densities (2 X 10(8) cells per ml) further inhibited killing. Multiphasic survival curves resulting after treatments in deionized water (pH 6.7) suggested the presence of cells with differing susceptibilities either at the start of treatment peri...

Moore, C. W.

1982-01-01

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Nuclear Waste Disposal in Space: BEP's Best Hope?  

International Nuclear Information System (INIS)

The best technology is worthless if it cannot find a market Beam energy propulsion (BEP) is a very promising technology, but faces major competition from less capable but fully developed conventional rockets. Rockets can easily handle projected markets for payloads into space. Without a new, huge demand for launch capability, BEP is unlikely to gain the resources it needs for development and application. Launching tens of thousands of tons of nuclear waste into space for safe and permanent disposal will provide that necessary demand while solving a major problem on earth. Several options exist to dispose of nuclear waste, including solar orbit, lunar orbit, soft lunar landing, launching outside the solar system, and launching into the sun

2006-05-02

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BEPS redesign of 168 commercial buildings: summary report  

Energy Technology Data Exchange (ETDEWEB)

The objective of this report is to present, in usable form, summary data from the Building Energy Performance Standards (BEPS) Phase II commercial buildings energy research conducted in 1978-1979. Summary data presented were obtained from two major research efforts: the BEPS Phase II Redesign experiment; and the related research on ASHRAE Standard 90-75R. The bulk of this report consists of data tabulations of key energy parameters for the 168 sample buildings, which were tabulated from computer-stored files of the 1978-1979 data. Two kinds of tabulations are included: numerical tabulations that extracted information from the computer-stored data base for the 168 sample buildings; and graphic presentations of the computer-generated data, plus data extracted from other sources. The intent is to provide a single data compendium of key energy-related factors from the 1978 redesign experiment and the associated 1978-1979 ASHRAE Standard 90-75R research. This report also supplements the information for which there was not space in the magazine articles. Thus, for some building types, additional analysis, comments, and data tabulations are included that could not be included in the articles because space was limited. These additional analysis items are not consistent across building types because both the energy conservation opportunities and the design strategies applied by the building designers varied considerably by building type. The chapters have been entered individually into EDB and ERA.

Stoops, J.L.; Deringer, J.J.; Moreno, S.; Misuriello, H.P.

1984-05-01

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BAT and BEP as instruments for reducing emissions of unintentionally produced POPs and development of guidelines under the Stockholm Convention.  

Science.gov (United States)

The 6th Intergovernmental Negotiating Committee (INC 6), under the Stockholm Convention on POPs, gave an expert group the mandate to develop guidelines for the application and implementation of best available techniques (BAT) and best environmental practices (BEP) for the prevention and reduction of unintentionally produced and emitted POPs, including polychlorinated dibenzodioxins/-furans (PCDD/Fs), polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB). Measures to reduce or eliminate the release of these POPs to the environment can be found in Article 5 of the Convention. BAT and BEP are already being applied as emission reduction instruments in a number of industrialised countries and are elements of other major international treaties, e.g. the UN ECE Protocol on POPs and the Marine Convention's OSPAR and HELCOM, and of the EU Directive for Integrated Pollution Prevention and Control (IPPC Directive). Existing concepts are presented and compared with the requirements of the Stockholm Convention. Consequences, perspectives and questions for the future intersessional work of the above-mentioned Expert Group are discussed. PMID:12943011

Richter, Steffi; Steinhäuser, Klaus Günter

2003-01-01

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DNA interaction with 57Co-bleomycin  

International Nuclear Information System (INIS)

Tumor-diagnostic 57Co-bleomycin is a mixture of two isomers: types I and II. Interaction between these and DNA was studied by fluorescence spectrometry and thermal denaturation. The fluorescence study indicated that cobalt chelation resulted in a remarkable increase in the apparent DNA-bleomycin association constant and a slight increase in bleomycin-DNA binding; a remarkable difference was observed between the two isomers. In the thermal denaturation study, the difference of DNA binding behavior was also observed. The tumor affinity of these isomers was slightly different, and type I isomer showed higher tumor affinity than type II. These results indicate that cobalt chelation to bleomycin enhances DNA-bleomycin binding and its DNA binding stability, and these mechanisms, although not fully understood, appear to underline the difference in tumor affinity of cobalt-bleomycin isomers. (orig.)

1982-12-01

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Assessment of BEP of MIMO-OFDMA systems  

Directory of Open Access Journals (Sweden)

Full Text Available MIMO antenna systems with OFDMA are used for high data rate systems for 4th generation wireless networks. Multi cell systems developed based on wireless standards such as WiMAX and 3GPP LTE. In this paper we are calculating average BEP (bit error probability of MIMO-OFDMA systems. Multiuser access scenarios are two types those are co-ordination and randomization. For interference mitigation in co-ordinated scenario we arrange ULA (uniform linear array with closely spaced antennas and beamforming process and in randomization we arrange OSTBC (orthogonal space time block coding with antennas sufficiently spaced apart. Numerical results of analytical frame work is used for different applications and wide range system configurations.

Manohar Naik Ramavath#1 B.A.Sarath Manohar Babu

2013-09-01

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Bleomycin lung: a case report  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A 69-year-old gentleman with non-Hodgkin’s lymphoma (stage I), with baseline fibrotic lung changes on CT, received six cycles of R-PMitCebo chemotherapy containing bleomycin. Three months later he presented to the Accident and Emergency Department with progressive dyspnoea, dry cough, pyrexia and generalised lethargy. Chest radiographs showed bilateral lower zone opacities. Clinically, all signs initially pointed to community-acquired penumonia, but he failed to respond to standard treatmen...

Rashid, Rabia Sofia

2009-01-01

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Different iron(II) complexes of bleomycin A2  

International Nuclear Information System (INIS)

By _1_3C-nmr on iron-bleomycin preparations, an iron-bleomycin-CO complex is found that loses its CO upon standing, as demonstrated using _1_4CO. Iron-bleomycin, prepared without rigorous exclusion of oxygen, reacts with CO to a stable diamagnetic iron-bleomycin-CO complex

1982-01-01

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Scintigraphy of ORL tumours with cobalt bleomycin  

International Nuclear Information System (INIS)

Our experiences with cobalt bleomycin scintigraphy in the treatment planning of ORL tumors are described. 142 scintigrams taken from 127 patients have been examined. As is shown by our investigation, cobalt bleomycin scintigraphy is a good examination method, however, too much expenditure is needed to have the necessary data for therapy planning. To our opinion, the information obtained in oto-rhino-laryngology by an exact clinical examination is as good as that of cobalt bleomycin scintigraphy. Our treatment schemes had only to be revised in some exceptional cases. (orig.)

1986-01-01

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Scintigraphy of ORL tumours with cobalt bleomycin  

Energy Technology Data Exchange (ETDEWEB)

Our experiences with cobalt bleomycin scintigraphy in the treatment planning of ORL tumors are described. 142 scintigrams taken from 127 patients have been examined. As is shown by our investigation, cobalt bleomycin scintigraphy is a good examination method, however, too much expenditure is needed to have the necessary data for therapy planning. To our opinion, the information obtained in oto-rhino-laryngology by an exact clinical examination is as good as that of cobalt bleomycin scintigraphy. Our treatment schemes had only to be revised in some exceptional cases.

Willi, A.; Adaman, O.; Wespi, H.H.; Bekier, A.; Luetolf, U.M.

1986-11-01

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BEP-relations for N2 dissociation over stepped transition metal and alloy surfaces  

DEFF Research Database (Denmark)

We present density functional theory (DFT) calculations for N(2) dissociation on stepped face-centred cubic (211) surface slabs. By using the same crystal structure, the same adsorption site for atomic nitrogen, and the same transition-state bond length of N(2) over a range of pure metal surfaces, a perfectly linear Bronsted-Evans-Polanyi (BEP) relation between the transition-state potential energy and the dissociative chemisorption energy is obtained. The perfect BEP relation, which extends over 12 eV in chemisorption energy, suggests that the manifestation of BEP relations for surface reactions is a general electronic structure effect, and that geometric effects are responsible for the scatter which is normally observed around the BEP line. The BEP relation is also shown to be valid for both surface and bulk alloys. The scatter is, however, larger than for the pure elements. This can be understood as a larger geometrical variance. To analyze the accuracy of the DFT calculations a detailed convergence study is performed for several adsorbates on stepped hexagonal close-packed and face-centred cubic Ru slabs.

Fronczek-Munter, Ture Rønved; Bligaard, Thomas

2008-01-01

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Protease homolog BepA (YfgC) promotes assembly and degradation of ?-barrel membrane proteins in Escherichia coli  

Science.gov (United States)

Gram-negative bacteria are equipped with quality-control systems for the outer membrane (OM) that sense and cope with defective biogenesis of its components. Accumulation of misfolded outer membrane proteins (OMPs) in Escherichia coli leads to activation of ?E, an essential alternative ? factor that up-regulates transcription of multiple genes required to preserve OM structure and function. Disruption of bepA (formerly yfgC), a ?E-regulated gene encoding a putative periplasmic metalloprotease, sensitizes cells to multiple drugs, suggesting that it may be involved in maintaining OM integrity. However, the specific function of BepA remains unclear. Here, we show that BepA enhances biogenesis of LptD, an essential OMP involved in OM transport and assembly of lipopolysaccharide, by promoting rearrangement of intramolecular disulfide bonds of LptD. In addition, BepA possesses protease activity and is responsible for the degradation of incorrectly folded LptD. In the absence of periplasmic chaperone SurA, BepA also promotes degradation of BamA, the central OMP subunit of the ?-barrel assembly machinery (BAM) complex. Interestingly, defective oxidative folding of LptD caused by bepA disruption was partially suppressed by expression of protease-active site mutants of BepA, suggesting that BepA functions independently of its protease activity. We also show that BepA has genetic and physical interaction with components of the BAM complex. These findings raised the possibility that BepA maintains the integrity of OM both by promoting assembly of OMPs and by proteolytically eliminating OMPs when their correct assembly was compromised.

Narita, Shin-ichiro; Masui, Chigusa; Suzuki, Takehiro; Dohmae, Naoshi; Akiyama, Yoshinori

2013-01-01

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Protease homolog BepA (YfgC) promotes assembly and degradation of ?-barrel membrane proteins in Escherichia coli.  

Science.gov (United States)

Gram-negative bacteria are equipped with quality-control systems for the outer membrane (OM) that sense and cope with defective biogenesis of its components. Accumulation of misfolded outer membrane proteins (OMPs) in Escherichia coli leads to activation of ?(E), an essential alternative ? factor that up-regulates transcription of multiple genes required to preserve OM structure and function. Disruption of bepA (formerly yfgC), a ?(E)-regulated gene encoding a putative periplasmic metalloprotease, sensitizes cells to multiple drugs, suggesting that it may be involved in maintaining OM integrity. However, the specific function of BepA remains unclear. Here, we show that BepA enhances biogenesis of LptD, an essential OMP involved in OM transport and assembly of lipopolysaccharide, by promoting rearrangement of intramolecular disulfide bonds of LptD. In addition, BepA possesses protease activity and is responsible for the degradation of incorrectly folded LptD. In the absence of periplasmic chaperone SurA, BepA also promotes degradation of BamA, the central OMP subunit of the ?-barrel assembly machinery (BAM) complex. Interestingly, defective oxidative folding of LptD caused by bepA disruption was partially suppressed by expression of protease-active site mutants of BepA, suggesting that BepA functions independently of its protease activity. We also show that BepA has genetic and physical interaction with components of the BAM complex. These findings raised the possibility that BepA maintains the integrity of OM both by promoting assembly of OMPs and by proteolytically eliminating OMPs when their correct assembly was compromised. PMID:24003122

Narita, Shin-ichiro; Masui, Chigusa; Suzuki, Takehiro; Dohmae, Naoshi; Akiyama, Yoshinori

2013-09-17

 
 
 
 
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New determination of the 7Be(p,?)8B S-factor  

International Nuclear Information System (INIS)

We present new measurements of the 7Be(p,?)8B cross section from E-bar cm=116 to 2460 keV. Our new measurements lead to S17(0)=22.1+/-0.6(expt)+/-0.6(theor)eV-bar b based on data from E-bar cm=116 to 362 keV, where the central value is based on the theory of Descouvemont and Baye. We compare our results to other S17(0) values extracted from both direct (7Be(p,?)8B) and indirect (Coulomb dissociation and heavy-ion reaction) measurements, and show that the results of these 3 types of experiments are not mutually compatible. We recommend a 'best' value, S17(0)=21.4+/-0.5(expt)+/-0.6(theor)eV-bar b, based on the mean of all modern direct measurements below the 1+ resonance

2004-12-27

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Indirect measurement of 9Be(p, ?)6Li reaction by means of Trojan Horse Method  

International Nuclear Information System (INIS)

The beryllium abundance acts as a key role for understanding the inhomogeneous Big Bang nucleosynthesis. In order to measure the 9Be(p, ?)6Li bare nucleus cross section and S(E) factor at astrophysical energies, the Trojan Horse Method (THM) can be applied. The main feature of the method is that it allows to extract the energy dependence for the astrophysical S(E) factor of bare nuclei at very low energies without any extrapolation, by measuring the cross section of an appropriate three body process. Thus the 9Be(p, ?)6Li has been studied by means of the THM applied to the 2H(9Be, ?6Li)n at INFN-LNS, Catania, Italy. The two body reaction cross section has been studied in the energy range of Ecm=0-1000 keV, Preliminary results are discussed and a comparison with direct data is made. (authors)

2005-09-01

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New charge exchange model of GEANT4 for $^{9}$Be(p, n)$^{9}$B reaction  

CERN Multimedia

Taking ENDF/B-VII.1 differential cross section data as input, a new data-based charge exchange model of GEANT4 dedicated to the $^{9}$Be(p, n)$^{9}$B reaction is developed. The resulting model turns out to be in good agreement with the experimental data for the neutron yield spectrum, making significant improvement compared to other GEANT4 hadronic models.

Shin, Jae Won

2014-01-01

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Oxidative damage of BEP2D cells irradiated 60Co ?-rays  

International Nuclear Information System (INIS)

Objective: To study reactive oxygen species (ROS) productions and oxidative DNA damage in HPV-16 immortalized human bronchial epithelial cells (BEP2D) irradiated with 60Co ?-rays. Methods: The measurement of extracellular superoxide anions was based on the reduction of ferricytochrome C as assayed by the increase in its absorbance at 550 nm. Quantitation of extracellular hydrogen peroxides (H2O2) was based on the horseradish peroxidase-dependent oxidation of phenol red which is assayed by its increased absorbance at 620 nm. The determination of extracellular hydroxyl radicals (·OH) was based on de-coloration of safranine T as assayed by the decrease in its absorbance at 520 nm. Ethidium bromide and 2', 7'-dichlorofluorescein, fluorescent products of the membrane-permeable dyes-hydro-ethine and 2', 7'-dichlorofluorescein diacetate, were used to monitor the intracellular production of H2O2 and superoxide anions respectively by flow cytometry. 8-hydroxy-deoxygunosine (OH8dG) was examined with HPLC-ECD from extracted DNA. Results: the ROS production including H2O2, superoxide anions and ·OH, and DNA adduct OH8dG in 60Co ?-rays-irradiated BEP2D cells increased remarkably, and these increments could be inhibited effectively by 1 ?mol/L of selenium. Conclusion: 60Co ?-irradiation causes oxidative damage to BEP2D cells, which can be protected by selenium

2000-08-01

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Business Energy Plan (BEP-I) of the mental health care centre Losserhof in Almelo, Netherlands; Bedrijfs Energie Plan (BEP-I) van de Losserhof  

Energy Technology Data Exchange (ETDEWEB)

In 1995 a long-range agreement (MJA, abbreviated in Dutch) between the Dutch government and the title centre to improve the energy efficiency by 30% in the year 2000, compared to the year 1989. One of the obligations of a MJA is to draft a Business Energy Plan (BEP) in which an overview is given of the energy consumption in the past and in the future, and the energy saving measures that were taken in the period 1989-1995 and will be taken in the period 1996-2000. Also attention is paid to a motivation campaign and the notion Good Housekeeping by means of which energy can be saved effectively and cheap

Kaalverink, R.; Van Rees, C.

1997-05-01

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Stress Linearization and Strength Evaluation of the BEP's Flow Plates for a Dual Cooled Fuel Assembly  

Energy Technology Data Exchange (ETDEWEB)

A fuel assembly is composed of 5 major components, such as a top end piece (TEP), a bottom end piece (BEP), spacer grids (SGs), guide tubes (GTs) and an instrumentation tube (IT) and fuel rods (FRs). There are no ASME criteria about all components except for a TEP/BEP. The TEP/BEP should satisfy stress intensity limits in case of condition A and B of ASME, Section III, Division 1 . Subsection NB. In a dual cooled fuel assembly, the array and position of fuels are changed from those of a conventional PWR fuel assembly to achieve a power uprating. The flow plates of top/bottom end pieces (TEP/BEP) have to be modified into proper shape to provide flow holes to direct the heated coolant into/out of the fuel assembly but structural intensity of these plates within a 22.241 kN axial loading should satisfy Tresca stress limits in ASME code. In this paper, stress linearization procedure and strength evaluation of a newly designed BEP for the dual cooled fuel assembly are described.

Kim, Jae Yong; Yoon, Kyung Ho; Kang, Heung Seok; Lee, Young Ho; Lee, Kang Hee; Kim, Hyung Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2009-10-15

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7Be(p,?)8B cross section and the properties of 7Be  

International Nuclear Information System (INIS)

We study the nonresonant part of the 7Be(p,?)8B reaction using a three-cluster resonating group model that is variationally converged and virtually complete in 4He+3He+p model space. The importance of using adequate nucleon-nucleon interaction is demonstrated. We find that the low-energy astrophysical S factor is linearly correlated with the quadrupole moment of 7Be. A range of parameters is found where the most important 8B, 7Be, and 7Li properties are reproduced simultaneously; the corresponding S factor at Ec.m.=20 keV is 24.6--26.1 eV b

1995-08-01

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Study of the 9Be(p,?)6Li reaction via the Trojan Horse Method  

International Nuclear Information System (INIS)

The Trojan Horse Method has been applied to the 2H(9Be,6Li?)n three-body reaction in order to investigate the 9Be(p,?)6Li two-body reaction, which is involved in the study of light element abundances (lithium, beryllium and boron). A coincidence measurement was performed in order to identify the presence of the quasi-free mechanism in the three-body reaction, needed for the application of the method. The astrophysical S(E)-factor was extracted and compared to direct data. No information about electron screening effects can be extracted due to the poor resolution of the indirect data. (orig.)

2006-03-01

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BEP/SEP and Outage Performance Analysis of L-Branch Maximal-Ratio Combiner for ??? Fading  

Directory of Open Access Journals (Sweden)

Full Text Available Maximal-ratio combiner (MRC performances in fading channels have been of interest for a long time, which can be seen by a number of papers concerning this topic. In this paper we treat bit error probability (BEP, symbol error probability (SEP and outage probability of MRC in presence of ??? fading. We will present ??? fading model, probability density function (PDF, and cumulative distribution function (CDF. We will also present PDF, CDF, and outage probability of the L-branch MRC output. BEP/SEP will be evaluated for broad class of modulation types and for coherent and noncoherent types of detection. BEP/SEP and outage performances of the MRC will be evaluated for different number of branches via Monte Carlo simulations and theoretical expressions.

Mirza Miliši?

2009-01-01

30

Fluoromicroscopic studies of bleomycin-induced intracellular oxidation in alveolar macrophages and its inhibition by taurine.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The mechanism of bleomycin-induced pulmonary fibrosis is not yet clear. Recent studies have shown that alveolar macrophages (AM) can be stimulated by bleomycin in vitro releasing inflammatory cytokines, suggesting that the interaction of bleomycin with AM is an important step in the drug-induced fibrotic process. Bleomycin is known to bind DNA and generate oxygen radicals through complexation with Fe2+ and oxygen. To provide more insight into the cellular oxidative property of bleomycin, we h...

1994-01-01

31

Trojan horse method applied to 9Be(p,?)6Li at astrophysical energies  

International Nuclear Information System (INIS)

The low-energy bare-nucleus cross section for 9Be(p,?)6Li has been extracted by means of the Trojan horse method (THM) applied to the 2H(9Be, ?,6Li)n reaction at a beam energy of 9Be of 22.35 MeV. For the first time, we assume an intermediate process, 9Be+2H?9Be+p+n, and considered this process as one criterion of the quasifree condition. Accordingly, sequential decay processes were eliminated. The derived astrophysical S(E) factor for the two-body process 9Be(p,?)6Li is compared with that obtained from direct experiments. We have found good agreement between the two results, leading to an improved determination of the S(E) with S(0)=21.0±0.8 MeV b. Furthermore, the electron screening potential energy Ue=676±86 eV has also been extracted in a model-independent way by comparing the direct and THM data. The value is significantly higher than that predicted by current theoretical models, whereas it is lower than Ue?830 eV, which was extracted from direct measurements with inclusion of the Ec.m.=-23 keV subthreshold resonance

2008-09-01

32

Proteome analysis for effects of radiation on BEP2D cell  

International Nuclear Information System (INIS)

The study analyzed the differential expression of proteins profile of the normal BEP2D cell and the BEP2D cell radiated with 1.5 Gy, 3 Gy ? rays by Proteomics technique. The results showed that approximately 1000 analyzed proteins per 2-D gel were isolated with molecular weights ranging between 14.4-94 kD and pI 3-10. Image analysis showed that irradiation with 1.5 Gy ?-rays contracting with control image caused down-regulation of 104 kinds of cell proteins and up-regulation of 15 proteins. Irradiation with 3 Gy ?-rays contracting with control image caused down-regulation of 144 kinds of cell proteins and up-regulation of 26 proteins. Irradiation with the two dimensional electrophoresis contracting with control image both caused down-regulation of 15 kinds of cell proteins and up-regulation of 3 proteins. Using mass spectrometry, a protein MLC was identified within the two protein spots (spot D and spot 660). All of this change of proteins expressing may result in the lung cancer, and the study can provide baisis for the study of lung cancer pathogenesis. (authors)

2009-07-01

33

Indirect measurement of bare astrophysical S(E) factor for 9Be(p,?)6Li  

International Nuclear Information System (INIS)

The beryllium abundance acts as a key role for understanding the inhomogeneous Big Bang nucleosynthesis. In order to measure the 9Be(p,?)6Li bare nucleus cross section and S(E) factor at astrophysical energies, the Trojan Horse Method (THM) can be applied. The method can overcome the difficulties caused by Coulomb barrier and electronic screening effect in direct measurement, and it allows to extract the energy dependence for the bare astrophysical S(E) factor at very low energies without any extrapolation by measuring the cross section of an appropriate three body process under the quasi-free condition. The 9Be(p,?)6Li has been studied by means of the THM applied to the 2H(9Be,?6Li)n at China Institute of Atomic Energy. The two body reaction cross section and S(E) factor was extracted in the energy range of Ecm=0-300 keV. The electron screening potential Ue was then obtained by comparing the THM data with the direct ones. (authors)

2010-11-01

34

Distribution of Fe-bleomycin, Co-bleomycin in tumor tissue  

International Nuclear Information System (INIS)

Ferric bleomycin (Fe-BLM) complex was found stable in the region of BLM excess and in the region of pH greater than 4.8. When this was injected intravenously into a mouse, it did not dissociate during the period of observation. Localization of Fe-BLM complex in mammary carcinoma of the C3H mouse and MC-induced squamous cell carcinoma was investigated by histochemical analysis of iron. In the tumor tissue, the iron as was identified by the Berlin blue reaction was seen localized in the stroma cells, histiocyte-like cells in granulation tissue and hair roots, but not in the tumor nests. On the contrary, Co-BLM was seen localized in the tumor nests, especially in the nuclear part of the tumor cells as investigated by cobalt straining. There was a clear-cut difference in the distribution pattern between 59Fe-BLM and 60Co-BLM. While Fe-BLM retained much of ''bleomycin'' character, the Co-BLM behaved like cobalt itself in vivo in the mouse. Thus, the chelating metal would greatly influence the distribution pattern of bleomycin. (auth.)

1977-01-01

35

Cleavage of bleomycin hydrolase by caspase-3 during apoptosis.  

Science.gov (United States)

Bleomycin hydrolase (BLH) affects bleomycin chemotherapy through inactivation of bleomycin with deamination. As a neutral cysteine protease, it also plays various roles in physiological conditions and diseases. However, its mechanism of degradation remains unclear. In the present study, we showed that the levels of BLH were significantly reduced during apoptosis induced by the antitumor agents bleomycin, etoposide and hydroxycamptothecin, and inhibited by the caspase inhibitors Q-VD-oph and Z-DEVD-FMK. Furthermore, the caspase-dependent cleavage of BLH was confirmed by cleavage of partly-purified human BLH with caspase-3 and caspase-9 in vitro. The stability of BLH at normal culture conditions was analyzed with the protein synthesis inhibitor cycloheximide and the proteasome inhibitor MG132. BLH was degraded at a rate lower than that of cyclin D1. This is the first report to demonstrate that BLH is cleaved by caspase-3 during apoptosis. PMID:23708668

Chen, Yang; Xu, Rong; Chen, Jianguo; Li, Xiaoyu; He, Qiyang

2013-08-01

36

Mutation of p53 gene in human bronchial epithelial cells BEP2D induced by ?-particles  

International Nuclear Information System (INIS)

Objective: To detect p53 gene mutation in BEP2D cells induced by ?-particles. Methods: Analysis of genomic DNA from the transformed cells using PCR amplification and single strand conformation polymorphism (SSCP). Results: SSCP and restriction enzyme analysis demonstrated a point mutation at codon 249 of tumor suppressor gene p53 which has been thought to be the 'hotspot' of mutation in transformation induced by ?-particles. Southern blot analysis showed a deletion in exon 5/6 of p53 gene, but there was no mutation in the exon 8/9 of p53 gene. Conclusion: p53 gene is the 'target' of DNA lesions induced by ?-particles. It plays an important role in the process of transformation of bronchial epithelial cells induced by ?-irradiation

2001-04-01

37

Repetitive intratracheal bleomycin models several features of idiopathic pulmonary fibrosis  

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Single-dose intratracheal bleomycin has been instrumental for understanding fibrotic lung remodeling, but fails to recapitulate several features of idiopathic pulmonary fibrosis (IPF). Since IPF is thought to result from recurrent alveolar injury, we aimed to develop a repetitive bleomycin model that results in lung fibrosis with key characteristics of human disease, including alveolar epithelial cell (AEC) hyperplasia. Wild-type and cell fate reporter mice expressing ?-galactosidase in cell...

Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Mcmahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

2010-01-01

38

Asymptotic normalization coefficients for {sup 10}B{r_arrow}{sup 9}Be+p  

Energy Technology Data Exchange (ETDEWEB)

The differential cross sections for the reactions {sup 9}Be({sup 10}B,{sup 10}B){sup 9}Be and {sup 9}Be({sup 10}B,{sup 9}Be){sup 10} B have been measured at an incident energy of 100 MeV. The elastic scattering data have been used to determine the optical model parameters for the {sup 9}Be+{sup 10}B system at this energy. These parameters are then used in distorted-wave Born approximation (DWBA) calculations to predict the cross sections of the {sup 9}Be({sup 10}B,{sup 9}Be){sup 10}B proton exchange reaction, populating the ground and low-lying states in {sup 10}B. By normalizing the theoretical DWBA proton exchange cross sections to the experimental ones, the asymptotic normalization coefficients (ANC`s), defining the normalization of the tail of the {sup 10}B bound state wave functions in the two-particle channel {sup 9}Be+p, have been found. The ANC for the virtual decay {sup 10}B(g.s.){r_arrow}{sup 9}Be+p will be used in an analysis of the {sup 10}B({sup 7}Be,{sup 8}B){sup 9}Be reaction to extract the ANC`s for {sup 8}B{r_arrow}{sup 7}Be +p. These ANC`s determine the normalization of the {sup 7}Be(p,{gamma}){sup 8}B radiative capture cross section at very low energies, which is crucially important for nuclear astrophysics. {copyright} {ital 1997} {ital The American Physical Society}

Mukhamedzhanov, A.M.; Clark, H.L.; Gagliardi, C.A.; Lui, Y.; Trache, L.; Tribble, R.E.; Xu, H.M.; Zhou, X.G. [Cyclotron Institute, Texas AM University, College Station, Texas 77843 (United States); Burjan, V.; Cejpek, J.; Kroha, V. [Institute for Nuclear Physics, Czech Academy of Sciences, Prague-Rez (Czech Republic); Carstoiu, F. [Institute of Atomic Physics, Bucharest (Romania)

1997-09-01

39

Precise measurement of the 7Be(p,?)8B S factor  

International Nuclear Information System (INIS)

We present new measurements of the 7Be(p,?)8B cross section from Ec.m.=116 to 2460 keV (where c.m. means center-of-mass), which incorporate several improvements over our previously published experiment, also discussed here. Our new measurements lead to S17(0)=22.1±0.6(expt)±0.6(theor) eV b based on data from Ec.m.=116 to 362 keV, where the central value is based on the theory of Descouvemont and Baye. The theoretical error estimate is based on the fit of 12 different theories to our low-energy data. We compare our results to other S17(0) values extracted from both direct [7Be(p,?)8B] and indirect (Coulomb-dissociation and heavy-ion reaction) measurements, and show that the results of these three types of experiments are not mutually compatible. We recommend a 'best' value, S17(0)=21.4±0.5(expt)±0.6(theor) eV b, based on the mean of all modern direct measurements below the 1+ resonance. We also present S factors at 20 keV which is near the center of the Gamow window: the result of our measurements is S17(20)=21.4±0.6(expt)±0.6(theor) eV b, and the recommended value is S17(20)=20.6±0.5(expt)±0.6(theor) eV b

2003-12-01

40

Cytogenetic analysis of malignant transformants of human bronchial epithelial cells BEP2D generated by ?-particles exposure  

International Nuclear Information System (INIS)

Objective: To analyze the cytogenetic changes in malignant transformants of human bronchial epithelial cell line (BEP2D) generated by ?-particles exposure. Methods: Tumor cell lines were derived from nude mice bearing malignant transformed cells generated from cells of passage 35 of 1.5 Gy ?-particles-irradiated BEP2D cells. G-banding patterns of chromosomes was used to analyze the karyotypes. Results: Five individual malignant transformed cell lines were analyzed. Deletions of one copy of chr13 and chrY, and an unidentified fragment attached to the long arms of chr2 and chr12 respectively (chr2q+, chr12q+) were observed in all the malignant transformed cell lines. The proportion of polyploid of BERP35T-2 and BERP35T-4 cells was about 40% and was higher than that of PEB2D cells (5%). Conclusions: The process of cellular malignant transformation induced by ?-particles exposure could involve some characteristic cytogenetic changes

2002-06-01

 
 
 
 
41

Synthesis of non-ionic and ionic resins for BEP intaglio inks curing by electron-beam radiation. Annual report  

International Nuclear Information System (INIS)

The inks currently used to print US postage stamps on web presses are dried by heat evaporation of solvents. Emission of solvents into the atmosphere is governed by Local and Federal Government Regulations. Reduction of these emissions to acceptable levels can be accomplished by either of two methods available to the BEP. The work was part of a continuing effort to produce resins for use in formulation of intaglio inks for the printing of postage stamps and security documents. The inks are to be cured by exposure to an electron beam. The uncured inks are cleaned from the roller and wiping blade by washing the wiping blade with neutral water or with caustic water. Laboratory scale work on the urethane/polyethylene oxide/methacrylate resins has now been concluded and information on the synthesis has been provided to BEP for patenting and scaleup. Some effort on nonionic resins continued into FY88

1992-01-01

42

An angular momentum selection rule and the "9Be(?"+,p)"8Be reaction at 50 MeV  

International Nuclear Information System (INIS)

Angular distributions have been measured at 50 MeV for the "9Be(?"+,p)"8Be reaction leading to the 0"+, 2"+ and 4"+ states of "8Be. An angular momentum selection rule is considered in order to account for the preferential excitation of high spin states. Two-step processes in the framework of the DWBA and momentum sharing in the two-nucleon model are also discussed

1980-01-01

43

Expression of bleomycin hydrolase in keratinization disorders.  

Science.gov (United States)

A neutral cysteine protease, bleomycin hydrolase (BH), is widely expressed in mammalian tissues, with the skin seeming to contain the highest level. Our previous study revealed that BH transcription is modulated both during differentiation and by cytokines. However, BH involvement in keratinization disorder is not well known. In the present study, we performed immunohistochemical studies of BH and other serine/cysteine proteases in human normal skin and lesional skin with keratinization disorders. BH-positive cells were detected in granular layers of orthokeratotic and hyperkeratotic skin diseases, such as erythrokeratoderma and lichen planus. In parakeratotic skin diseases with porokeratosis, pityriasis rubra pilaris and psoriasis, BH staining was decreased in lesional skins compared to that in normal skin. Similar results were obtained for cysteine proteases, caspase-14 and calpain I. On the other hand, cells positive for serine proteases kallikrein 5 and 7 were increased in parakeratotic and inflammatory skin diseases, such as psoriasis. Semi-quantification analysis revealed that BH- and caspase-14-positive staining had higher intensity than those of the other proteases in normal epidermis. As BH is the major citrulline aminopeptidase in normal granular layer, the alternation would have a significant effect on terminal differentiation processes, such as aberrant processing of deiminated peptides. Therefore, BH may play an important role during the late stage of epidermal differentiation. PMID:22037625

Kamata, Yayoi; Maejima, Hideki; Watarai, Akira; Saito, Norimitsu; Katsuoka, Kensei; Takeda, Atsushi; Ishihara, Kazuhiko

2012-01-01

44

Detection of lung cancer with 55Co-bleomycin using a positron camera  

International Nuclear Information System (INIS)

57Co-bleomycin is useful in the detection and staging of lung cancer, but the long half-life of 57Co(270 days) has discouraged its widespread acceptance. We investigated the shorter living positron emitting 55Co(half-life 18.2 h) as a label for bleomycin. In eleven patients with proven lung cancer scintigraphy with 55Co-bleomycin, using a positron camera, demonstrated the tumor in ten cases. Tumor to lung ratios were calculated. The results were superior to those obtained with 55Co-bleomycin single photon imaging but inferior to those obtained with 57Co-bleomycin scintigraphy. (orig.)

1982-01-01

45

Distribution of 64Cu-Bleomycin in normal and tumor-bearing rats  

International Nuclear Information System (INIS)

Accumulation of a radioactive label in tumor tissue is required for scintigraphic visualization of the tumor and has been achieved by application of bleomycin as carrier. This chemotherapeutic polypeptide drug has been labeled with 64Cu. Thin layer chromatography of 64Cu-bleomycin which was incubated for 22 hours at 370C showed no changes of the chelate. When urine of the 64Cu-bleomycin treated animals was chromatographed considerable amounts (9.3%) of free 64Cu appeared 2 hours after injection of the chelate and dissociation was found to be almost complete 4 hours after injection of labeled bleomycin. The distribution of 64Cu-bleomycin is similar to that found with sup(99m)Tc-bleomycin with long lasting accumulation in kidneys and liver. Highest concentration ratios of the activity in mesenchymal tumor (Yoshida) and blood respectively were found 6 hours after intravenous administration of 64Cu-bleomycin. (author)

1976-01-01

46

Fe.bleomycin as a probe of RNA conformation.  

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Two crystallographically defined tRNAs, yeast tRNAAsp and tRNAPhe, were used as substrates for oxidative cleavage by Fe.bleomycin to facilitate definition at high resolution of the structural elements in RNAs conducive to bleomycin binding and cleavage. Yeast tRNAAsp underwent cleavage at G45 and U66; yeast tRNAPhe was cleaved at four sites, namely G19, A31, U52 and A66. Only two of these six sites involved oxidative cleavage of a 5'-G.Pyr-3' sequence, but three sites were at the junction bet...

Holmes, C. E.; Abraham, A. T.; Hecht, S. M.; Florentz, C.; Giege?, R.

1996-01-01

47

Amino acid analysis and cell cycle dependent phosphorylation of an H1-like, butyrate-enhanced protein (BEP; H1"0; IP_2_5) from Chinese hamster cells  

International Nuclear Information System (INIS)

A fraction enriched in the butyrate-enhanced protein (BEP) has been isolated from Chinese hamster (line CHO) cells by perchloric acid extraction and Bio-Rex 70 chromatography. Amino acid analyses indicate that the composition of BEP resembles that of CHO H1; however, BEP contains 11% less alanine than H1, and, in contrast to H1, BEP contains methionine. Treatment of BEP with cyanogen bromide results in the cleavage of a small fragment of approx. 20 amino acids so that the large fragment seen in sodium dodecyl sulfate-acrylamide gels has a molecular weight of approx. 20,000. Radiolabeling and electrophoresis indicate that BEP is phosphorylated in a cell cycle dependent fashion. These data suggest that (1) BEP is a specialized histone of the H1 class and (2) BEP is the species equivalent of calf lung histone H1"0, rat H1"0, and IP_2_5, a protein enhanced in differentiated Friend erythroleukemia cells. The data also indicate that putative HMG1 and HMG2 proteins do not undergo the extensive cell cycle dependent phosphorylations measured for histone H1 and BEP

1980-01-01

48

Bleomycin effect on L5178Y cells  

International Nuclear Information System (INIS)

We analyzed the effects of treatment with bleomycin (BLM) in 2 sublines of L5178Y (LY) murine lymphoma, LY-R, radioresistant, and LY-S, radiosensitive. LY-S cells were 2 times more sensitive to BLM than LY-R cells, similarly as in the case of X rays. Since there was no difference in the activity of drug transport system, this different susceptibility to BLM probably was due to the DNA repair defect in LY-S cells. Growth was impaired proportionally to the lethal effect and continued (days 3-6 after treatment with 50 microM BLM) until the elimination of dead cells from the cell population; 24 h after treatment cell cycle distributions indicated the presence of block in S phase (proportional to the dose of BLM). Contrarily to X or gamma-irradiation, BLM did not induce any block in the G2 phase. Initial DNA damage, estimated by the single cell gel electrophoresis, was linearly related to the dose of BLM in LY-S cells; in LY-R cells the damage level was significantly higher than in LY-S cells. In the higher (>10 microM BLM) dose range both dose - effect curves became identical. In gamma-irradiated LY-R and LY-S cells the dose - effect curves were identical. DNA damage distribution in BLM treated LY cells was much less uniform than in the gamma-irradiated ones; it indicated the presence of heavily damaged cells, a feature typical for BLM action. (author). 29 refs, 28 figs

1997-01-01

49

Flagellate dermatitis after bleomycin. A histological and immunohistochemical study.  

Science.gov (United States)

A case of flagellate dermatitis after administration of bleomycin is reported in a patient with Hodgkin's disease. Histopathological and immunohistochemical analysis revealed a drug-induced skin toxic reaction rather than a lymphomatous infiltrate. Pigmentary changes observed after the early erythematous eruption were due to a postinflammatory effect. PMID:1702587

Miori, L; Vignini, M; Rabbiosi, G

1990-12-01

50

Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice  

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The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.

Fujita, Masaki; Ye, Qing; Ouchi, Hiroshi; Harada, Eiji; Inoshima, Ichiro; Kuwano, Kazuyoshi; Nakanishi, Yoichi

2006-01-01

51

Excretion and organic distribution of _5_7Co-bleomycin emulsions  

International Nuclear Information System (INIS)

Excretion and organic distributions of _5_7Co-bleomycin were studied in normal and tumour-bearing mice with the objective of obtaining high _5_7Co-bleomycin concentrations in the tumour and the regional lymph nodes. Aqueous _5_7Co-bleomycin and various _5_7Co-bleomycin emulsions were used for the studies and applied either locally or systemically. Excretion of _5_7Co-bleomycin was slowest after local administration of _5_7Co-bleomycin oil-in-water emulsion and fastest after systemic application of aqueous _5_7Co-bleomycin. Organic distribution studies showed the highest values in the tumour and the regional lymph nodes after local injection of _5_7Co-bleomycin oil-in-water emulsion while the lowest values were measured after systemic application of aqueous _5_7Co-bleomycin. These kinetic studies suggest that intratumoral treatment with oil-in-water emulsions of bleomycin may be a new approach in the therapy of epithelial tumours with lymphogenic metastases. (orig.)

1982-01-01

52

NMR determination of the structures of peroxycobalt(III) bleomycin and cobalt(III) bleomycin, products of the aerobic oxidation of cobalt(II) bleomycin by dioxygen.  

Science.gov (United States)

The oxidation of Co(II) bleomycin A2 by dioxygen leads to two products, HO2-Co(III) bleomycin A2 (form I) and Co(III) bleomycin A2 (form II). 1H NMR chemical shift assignments for protons of both forms have been made by two-dimensional NMR spectral techniques. The chemical shifts of protons throughout forms I and II differ from each other and from apobleomycin A2. NOESY spectra reveal a number of intermediate and long-range 1H-1H couplings within the metal-binding domain, between the metal-binding domain and the peptide linker, which connects it and the DNA-binding region of the molecule, and, in form I, between the DNA- and metal-binding domains. Molecular dynamics calculations were carried out based on the NOESY results and an adjustable square pyramidyl ligand geometry around Co(III) composed of nitrogen atoms of the primary and secondary amine groups, pyridine (N5), and amide and imidazole (N1) of the hydroxyhistidine residue. In form I, the bithiazole group folds back across the square pyramid forming a compact structure. Although this conformational feature was not observed in form II, the peptide linker between the metal- and DNA-binding domains in both species shows extensive folding based on a large number of intramolecular interactions. PMID:7508261

Xu, R X; Nettesheim, D; Otvos, J D; Petering, D H

1994-02-01

53

Large angle proton emission in the "9Be(p,2p) reaction at 300 MeV  

International Nuclear Information System (INIS)

A "9Be(p,2p) coincidence experiment performed to to further elucidate the reaction mechanism for the production of energetic wide-angle protons in intermediate energy proton induced reactions is reported. Detectors in a coplanar geometry were used to measure coincidences between trigger protons at 90 degrees to the beam and forward angle protons on the opposite side of the beam. The incident proton energy was 300 MeV. The authors report both the inclusive spectra for the trigger protons and the differential mean multiplicities for the coincidence events

1983-01-01

54

Electromagnetic dissociation of 8B and the rate of the 7Be(p, ?)8B reaction in the sun  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In an effort to better determine the 7Be(p,?)8B reaction rate, we have performed inclusive and exclusive measurements of the Coulomb dissociation of 8B. The former was a study of longitudinal momentum distributions of 7Be fragments emitted in the Coulomb breakup of intermediate energy 8B beams on Pb and Ag targets. Analysis of these data yielded the E2 contribution to the breakup cross section. In the exclusive measurement, we determined the cross section for the Coulomb breakup of 8B on Pb ...

Davids, B.; Austin, Sm; Bazin, D.; Esbensen, H.; Sherrill, Bm; Thompson, Ij; Tostevin, Ja

2001-01-01

55

Overall normalization of the astrophysical S factor and the nuclear vertex constant for 7Be(p,?)8B reactions  

International Nuclear Information System (INIS)

We point out a simple relation between the nuclear vertex constant (NVC) and the overall normalization of the astrophysical S factor. Using predicted values of the NVC for the virtual decay of 8B ?7Be+p, we find S17(0) ?17.6 eV b for 7Be (p,?)8B reactions, consistent with the low values extrapolated from direct capture measurements by Filippone et al. and by Vaughn et al. New possibilities, using proton transfer reactions, to measure the astrophysical S factor indirectly are proposed

1994-10-10

56

Preparation and Quality Control of Scandium-46 Bleomycin as a Possible Therapeutic Agent  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Introduction: Due to interesting therapeutic properties of 46Sc and antineoblastic antibiotic, bleomycin (BLM), 46Sc-bleomycin (46Sc-BLM) was developed as a possible therapeutic compound. Methods: In this work, Sc-46 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1) of natural metallic scandium sample followed by dissolution in acidic media as a substitute for 47Sc in radiolabeling studies which was further used for labeling of bleomycin (BLM) followed by stability studies...

2012-01-01

57

Angiotensin-Converting Enzyme N-Terminal Inactivation Alleviates Bleomycin-Induced Lung Injury  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Bleomycin has potent anti-oncogenic properties for several neoplasms, but drug administration is limited by bleomycin-induced lung fibrosis. Inhibition of the renin-angiotensin system has been suggested to decrease bleomycin toxicity, but the efficacy of such strategies remains uncertain and somewhat contradictory. Our hypothesis is that, besides angiotensin II, other substrates of angiotensin-converting enzyme (ACE), such as the tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP), pl...

Li, Ping; Xiao, Hong D.; Xu, Jianguo; Ong, Frank S.; Kwon, Mike; Roman, Jesse; Gal, Anthony; Bernstein, Kenneth E.; Fuchs, Sebastien

2010-01-01

58

Static and dynamic mechanics of the murine lung after intratracheal bleomycin  

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Abstract Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods ...

Manali Effrosyni D; Moschos Charalampos; Triantafillidou Christina; Kotanidou Anastasia; Psallidas Ioannis; Karabela Sophia P; Roussos Charis; Papiris Spyridon; Armaganidis Apostolos; Stathopoulos Georgios T; Maniatis Nikolaos A

2011-01-01

59

Antineoplastic Activity of Chloroacetohydroxamic Acid in Combination with Bleomycin Against Ehrlich Ascites Carcinoma (EAC) in Mice  

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The research work has been undertaken in order to investigate the antineoplastic activity of chloroacetohydroxamic acid (CHA) in combination with bleomycin against Ehrlich ascites carcinoma (EAC) in Swiss Albino mice. Results showed that combination of treatment inhibits the tumor growth to more than 90% as against 56 and 65% for CHA and bleomycin, respectively. The combination treatment increases the life span of EAC bearing mice to 70% as against 30 and 50% for CHA and bleomycin, respective...

Khanam, J. A.; Masud Rana, A. Y. K. M.

2001-01-01

60

Study of the 9Be(p,?)6Li reaction by means of the Trojan Horse Method  

International Nuclear Information System (INIS)

In recent years the abundances of light elements lithium, beryllium and boron have been increasingly used in astrophysics as possible diagnostics between different scenario for primordial or stellar nucleosynthesis. The 9Be(p,?)6Li reaction represents one of the main ways for 9Be destruction in stellar environments and the measurements of its bare nucleus cross section in the energy region typical of such processes may provide a better knowledge of the beryllium abundance and its stellar destruction. This kind of measurements is very hard to be performed in a direct way because the energies of interest are much lower than the Coulomb barrier and usually an extrapolation procedure from data at higher energies is needed. The Trojan Horse method has been applied to the 2H(9Be,?6Li)n three body reaction in order to by-pass the difficulties of the direct measurement and the bare nucleus cross section of the 9Be(p,?)6Li two body reaction has been extracted in the 0-1 MeV energy range. Experimental procedure, data analysis and results will be discussed. (author)

2005-05-16

 
 
 
 
61

Antineoplastic Activity of Chloroacetohydroxamic Acid in Combination with Bleomycin Against Ehrlich Ascites Carcinoma (EAC in Mice  

Directory of Open Access Journals (Sweden)

Full Text Available The research work has been undertaken in order to investigate the antineoplastic activity of chloroacetohydroxamic acid (CHA in combination with bleomycin against Ehrlich ascites carcinoma (EAC in Swiss Albino mice. Results showed that combination of treatment inhibits the tumor growth to more than 90% as against 56 and 65% for CHA and bleomycin, respectively. The combination treatment increases the life span of EAC bearing mice to 70% as against 30 and 50% for CHA and bleomycin, respectively. The combination treatment also recovers the hematological parameters and alkaline phosphatase (ALP activity of tumor bearing mice more precisely than do CHA and bleomycin, individually.

J. A. Khanam

2001-01-01

62

PG490-88, a Derivative of Triptolide, Blocks Bleomycin-Induced Lung Fibrosis  

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In this study we evaluate the antifibrotic properties of PG-490-88, a water-soluble derivative of triptolide. Triptolide is an oxygenated diterpene that is derived from a traditional Chinese herb that has potent immunosuppressive and antitumor activity. We used the intratracheal bleomycin mouse model and found that PG490-88 inhibits fibrosis in the bleomycin group when given the same day or 5 days after bleomycin. PG490-88 also markedly reduced the number of myofibroblasts in the bleomycin tr...

Krishna, Ganesh; Liu, Kela; Shigemitsu, Hidenobu; Gao, Mingxing; Raffin, Thomas A.; Rosen, Glenn D.

2001-01-01

63

Radioiodinated bleomycin: stoichiometry of iodination and structural characterization by /sup 1/H-nuclear magnetic resonance  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin was iodinated by reaction with iodine monochloride (ICl). A direct relationship was found to exist between the average number of iodine atoms bound per molecule of bleomycin and the ICl:bleomycin molar ratio. Characterization by /sup 1/H-NMR analysis denoted that mono, di-, tri- and tetraiodobleomycin are formed when the reacting molar ratios, respectively, are 2:1, 4:1, 6.8:1 and 8.5:1 or greater. The sites of iodination of the bleomycin molecule have been identified to be the imidazole ring which iodinates first, followed by the bithiazole ring system which iodinates last.

Creekmore, J.R.; Kowalsky, R.J.; Kwock, L.; Wurster, D.E. (North Carolina Univ., Chapel Hill (USA). School of Medicine)

1984-03-01

64

Radioiodinated bleomycin: stoichiometry of iodination and structural characterization by 1H-nuclear magnetic resonance  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin was iodinated by reaction with iodine monochloride (ICl). A direct relationship was found to exist between the average number of iodine atoms bound per molecule of bleomycin and the ICl: bleomycin molar ratio. Characterization by 1H-NMR analysis denoted that mono, di-, tri- and tetraiodobleomycin are formed when the reacting molar ratios, respectively, are 2:1, 4:1, 6.8:1 and 8.5:1 or greater. The sites of iodination of the bleomycin molecule have been identified to be the imidazole ring which iodinates first, followed by the bithiazole ring system which iodinates last.

Creekmore, J.R.; Kowalsky, R.J.; Kwock, L.; Wurster, D.E.

1984-03-01

65

Stability of 111In-bleomycin in vivo - properties compared with 57Co-bleomycin  

International Nuclear Information System (INIS)

111Indium-belomycin (111In-BLM) and 57Co-bleomycin (57Co-BLM) were prepared and their distributions were compared in the tissues, blood, and urine in tumor-bearing and in untreated mice and rats. Autoradiographs of electrophoresis gels showed that patterns for urine from untreated and tumor-bearing animals, collected 1-3 h or 48 h after injection of 111In-BLM were similar to those for in vitro mixtures of urine and 111In-BLM, but differed from the patterns obtained with 111InCl3 under in vivo or in vitro conditions. In rats bearing mammary adenocarcinoma, 48 h after administration of the radio-pharmaceutical, the activity ratio of tumor to eleven different tissues was 1.2-4.6 times higher for injected 111In-BLM than for 111InCl3 (P111In-BLM than with 111InCl3. These findings were interpreted as reflecting the stability of 111In-BLM in vivo. The tumor concentration (%dose/g) was higher for the viable area than for the necrotic area for 111In-BLM, but the reverse was true for 57Co-BLM. (orig.)

1983-12-01

66

Re-186-bleomycine: Radiopharmaceutic for diagnosis and therapy  

International Nuclear Information System (INIS)

Bleomycine is an antibiotic used for chemotherapy of several neoplasms. Earlier studies with labelling of bleomycine (BLM) with different radionuclide were done. It was tested for different kind of tumours imaging. Due to previous encouraging imaging results with BLM-Tc-99m , BLM-Co-57 and BLM-In-111 authors decided to check the possibility and methods of labelling BLM with Re-186 to obtain radiopharmaceuticals potentially suitable for diagnosis and treatment of some neoplastic tumours. Different methods of labelling were investigated. The best one are electrolytic and with use of cationic-Sn complex modified by using of gentisic acid and incubation of the reaction mixture at 100 deg. C for 10 min. (author)

2001-06-01

67

Superoxide protects Escherichia coli from bleomycin mediated lethality  

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Superoxide and its products, especially hydroxyl radical, were recently proposed to be instrumental in cell death following treatment with a wide range of antimicrobials. Surprisingly, bleomycin lethality to Escherichia coli was ameliorated by a genetic deficiency of superoxide dismutase or by furnishing the superoxide generator plumbagin. Rescue by plumbagin was similar in strains containing or lacking recA or with inactive, inducible, or constitutive soxRS regulons. Thus, superoxide interfe...

Burger, Richard M.; Drlica, Karl

2009-01-01

68

Progress of bleomycin-induced lung fibrosis in rabbits.  

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Progression of lung fibrosis induced in rabbits by intratracheal bleomycin (BLM, 10 mg/kg) was monitored by biochemical and morphological measurements. These indicated that the evolution of fibrosis in the rabbit was slower than in other experimental animals. Histology revealed cellular and fibrocellular lesions 4 weeks after BLM. At 8 weeks these lesions still predominated, indicating continuing active disease accompanied by a progression to fibrosis. The gradual progression of the response ...

O Connor, C. M.; O Brien, A.; Sweeney, E. C.; Fitzgerald, M. X.

1986-01-01

69

Radiation doses from "5"1Cr-bleomycin  

International Nuclear Information System (INIS)

Extensive studies were made of long-term whole-body retention, plasma concentration and urinary excretion of "5"1Cr in rats, rabbits and patients after injection of "5"1Cr-bleomycin. Integrated whole-body and organ retention, corrected for radioactive decay, is similar in man and rabbit, and higher by a factor of about 2 in the rat. Doses to organs and whole body in man were calculated using the MIRD methodology and assuming conservatively that the kinetic data derived in rats are applicable to man. The organ and whole-body MIRD doses after "5"1Cr-bleomycin administration are comparable to those after "6"7Ga-citrate and the effective dose equivalent from a diagnostic amount of 740 MBq of the "5"1Cr complex amounts to about 6 mSv. However, the subcellular distribution in the liver of "5"1Cr, administered in the form of "5"1Cr-bleomycin, indicated a significant enrichment of "5"1Cr in the nuclei and in the DNA over mean concentrations in the liver cells. Also, the quality factor for Auger electrons, emitted by "5"1Cr, when assessed on the basis of the Q vs. LET relationship, as proposed by ICRP, was substantially higher than unity. Doses calculated for cell nuclei and the DNA in the liver cells were higher than the cell-averaged values by a factor 2.5 and 5, respectively, and the corresponding dose equivalents by a factor of 9 and 24. The effective dose equivalent, estimated on the basis of dose equivalents to cell nuclei and the DNA, amounted to 33 and 83 mSv per examination (740 MBq of "5"1Cr-bleomycin), respectively. (orig.)

1987-04-01

70

Cationic lipid:DNA complexes allow bleomycin uptake by melanoma cells.  

Science.gov (United States)

Bleomycin is a chemotherapeutic agent barely diffusible through the plasmatic membrane. We evaluated DNA/cationic lipids complexes (lipoplexes) as mediators of its uptake in four spontaneous canine melanoma derived cell lines (Ak, Bk, Br and Rkb). Cell survival after lipofection plus or minus bleomycin was determined by the acid phosphatase method and the cellular uptake of lipoplexes, carrying the E. coli ?-galactosidase gene, was evidenced by SYBR Green I staining. The four cell lines resulted sensitive to the bleomycin/lipoplexes system in both spatial configurations. Survival rates values were lower than 20% in monolayers of the four tested lines and lower than 30% in three lines (Ak, Bk and Rkb) when grown as spheroids. The sensitization to bleomycin depended on lipoplexes in Ak and Rkb while Bk (in both spatial configurations) and Br (as monolayers) were sensitive to bleomycin alone. Although some degree of sensitivity to bleomycin was induced by cationic lipids alone in Ak and Rkb monolayers, the maximal bleomycin effects appeared in the presence of lipoplexes. The sensitization was independent of transcriptional activity. The co-administration of lipoplexes diminished bleomycin IC50: 10-fold in Ak and Rkb monolayers; and sensitized the Ak and Rkb resistant spheroids. The bleomycin cytotoxic effects depended on lipoplexes concentration and diminished when cells were incubated at 8°C. Our results suggest that lipoplexes sensitize cells to bleomycin, increasing its uptake by an active transport mechanism, such as endocytosis. The bleomycin/lipoplexes system appears as a promising combination of chemotherapy and non-viral cancer gene therapy. PMID:23453489

Gil-Cardeza, María L; Rossi, Úrsula A; Villaverde, Marcela S; Glikin, Gerardo C; Finocchiaro, Liliana M E

2013-05-01

71

Study of the reactions 9Be(p, ?)6Li, 9Be(p,d)8Be from 300 keV to 900 keV  

International Nuclear Information System (INIS)

The experimental results concerning the two reactions 9Be(p,?)6Li and 9Be(p,d)8Be from 300 to 900 keV are presented. The angular distribution, excitation and total cross-section curves are expressed in absolute values after a normalization carried out using results given by Weber, Davis and Marion. (authors)

1968-01-01

72

Bleomycin 111In scanning: a new technique for detecting subclinical metastatic cancer  

International Nuclear Information System (INIS)

Preliminary experience shows bleomycin 111In to be a promising new tumor-scanning agent for earlier detection of subclinical metastatic disease with a low incidence of false-negative results. When the clinical findings are correlated with the scans and obvious areas of acute inflammation or edema are excluded, the bleomycin 111In scan becomes a highly valuable, atraumatic, clinical staging tool

1975-01-01

73

Extensive pneumothorax, pneumomediastinum and surgical emphysema as a complication of bleomycin therapy  

International Nuclear Information System (INIS)

Bleomycin is a commonly used chemotherapeutic agent and one of the commonest cytotoxic drugs leading to pulmonary parenchymal damage. It generally leads to interstitial pneumonitis and fibrosis, hypersensitivity reactions and acute respiratory distress syndrome. We describe an 8-year-old boy who, following prolonged bleomycin therapy, demonstrated extensive air dissection and extrapulmonary air, an unusual and fatal complication. (orig.)

2005-12-01

74

Preventive Effects of Pomegranate Seed Extract on Bleomycin-Induced Pulmonary Fibrosis in Rat  

Science.gov (United States)

Background Oxidative stress plays an important role in the pathogenesis of bleomycin-induced lung fibrosis and many antioxidant agents have been used for the treatment of this disease in animals. Objectives To evaluate the antioxidant effects of pomegranate seed extract (PSE) on bleomycin treated rats. Materials and Methods Male Spraque – Dawley rats were divided into 5 groups: rats in groups I (bleomycin) and II (control) were given a single dose of bleomycin (7.5 IU/kg, intratracheally) in the bleomycin group and same amount of saline in the control, respectively. Treatment groups (III-V) were given PSE (100,200,400 mg/kg) orally a week before the bleomycin injection and this was continued for 3 weeks. At day 28, animals were sacrificed and lungs were removed for histological investigation. Results Histological analysis showed that PSE could prevent pathological changes that were seen in the bleomycin group. Conclusions Results of the present study showed that hydroalcoholic extracts of pomegranate seeds had a significant protective effect against bleomycin-induced lung fibrosis by its antioxidant properties. The highest protective effect was observed for the 400 mg/kg dose.

Hemmati, Ali Asghar; Rezaie, Annahita; Darabpour, Pegah

2013-01-01

75

Effects of intratracheal instillation of bleomycin on phospholipid synthesis in hamster lung tissue slices  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin, an antineoplastic drug, is known to produce interstitial pulmonary fibrosis (IPF). As a result, it is commonly employed in various species to produce animal models of fibrosis. We have examined the uptake of (/sup 14/C) acetate by lung slices and its incorporation into lipids in the slices at various times following intratracheal administration of a fibrogenic dose of bleomycin in hamsters. As compared to saline controls, bleomycin had no effect on (/sup 14/C) acetate uptake at 4 and 7 days but it increased the uptake at 2 and 14 days after treatment. The incorporation of (/sup 14/C) acetate into total lipid was significantly reduced to 44, 62, 62, and 75% of the control at 2, 4, 7, and 14 days after bleomycin treatment, respectively. The incorporation into lipid as a percentage of the uptake was 12.2 in control animals whereas in bleomycin-treated animals, it was 4.7, 8.0, 7.3, and 6.9 at the corresponding times. Separation of lipids into various fractions revealed that bleomycin treatment specifically inhibited the synthesis of phosphatidylcholine and neutral lipid at all times of the study. The synthesis of all other phospholipids except phosphatidylethanolamine was depressed at 2 days. The latter was, however, depressed at 7 and 14 days after bleomycin treatment. It was concluded from the present study that bleomycin treatment inhibits the synthesis of phospholipid and neutral lipid and this may eventually lead to decreased surfactant production.

Giri, S.N.

1987-12-01

76

The sup 9 Be(p, gamma) sup 1 sup 0 B cross section at low energies  

CERN Document Server

Data for the sup 9 Be(p, gamma) sup 1 sup 0 B reaction with proton energies up to 1800 keV are fitted using R-matrix formulae that include channel contributions where appropriate. The data include values of the astrophysical S factor, the branching ratios for gamma-transitions to the four lowest states of sup 1 sup 0 B, angular distributions and analysing powers. Use is made of experimental values of asymptotic normalization constants obtained from sup 9 Be( sup 1 sup 0 B, sup 9 Be) sup 1 sup 0 B. A good fit is obtained with two 1 sup - levels, two 2 sup - levels, one 0 sup + level and one 2 sup + level.

Barker, F C

2002-01-01

77

Hydroxysafflor yellow A alleviates early inflammatory response of bleomycin-induced mice lung injury.  

Science.gov (United States)

Hydroxysafflor yellow A (HSYA) is an effective ingredient of Chinese herb Carthamus tinctorius L. The aim of this study was to evaluate the protective effect of HSYA on inflammatory phase of bleomycin-induced pulmonary injury in mice. Three doses of HSYA (26.7, 40, 60 mg/kg/d) were intraperitoneally injected to mice consecutively for 1 week after bleomycin administration. It was found that HSYA attenuated the loss in body weight, the increase of myeloperoxidase activity and pathologic changes of pulmonary inflammation caused by bleomycin. Treatment with HSYA also alleviated bleomycin-induced increase of mRNA level of tumor necrosis factor (TNF)-?, interleukin (IL)-1? and transforming growth factor (TGF)-?1 in lung homogenates. Moreover HSYA inhibited the increased activation of nuclear factor (NF)-?B and phosphorylation of p38 mitogen-activated protein kinases (MAPK) in lung tissue. These findings demonstrated that HSYA had protective effect on bleomycin-induced lung inflammatory response. PMID:22466555

Wu, Yan; Wang, Lin; Jin, Ming; Zang, Bao-xia

2012-01-01

78

Possibility to determine the astrophysical S factor for the 7Be(p,?)8B radiative capture from analysis of the 7Be(3He,d)8B reaction  

International Nuclear Information System (INIS)

At very low energies of astrophysical interest, the 7Be(p,?)8B reaction is almost totally peripheral. Consequently, the overall normalization of the cross section for this reaction is defined by the asymptotic normalization coefficient of the bound-state wave function of 8B in the two-body channel 7Be+p. The reaction 7Be(3He,d)8B is suggested as a tool to measure this asymptotic normalization coefficient thereby allowing one to define the absolute value of the astrophysical factor, S17(0), for the 7Be(p,?)8B reaction

1995-06-01

79

Work in progress: the effect of heat on bleomycin cytotoxicity in vitro and on the accumulation of 57Co-bleomycin in heat-treated rat tumors  

International Nuclear Information System (INIS)

The cytotoxic effects of the sequence and timing in combined hyperthermia and bleomycin treatment were tested in vitro using V79 Chinese hamster cells. The order of treatment was important; heat treatment followed by the administration of bleomycin yielded greater cytotoxicity than when the opposite order was used. To determine whether heat-treated tumors have an altered uptake of bleomycin, rat rhabdomyosarcoma (BA 1112) tumors were heated locally with RF current (43 degrees C, 90 min.), injected with 57Co-bleomycin, and imaged on a radioisotope camera. Results of tumor-to-background (T/B) ratio analysis indicate that local hyperthermia (43 degrees C) does not appear to alter tumor uptake patterns of 57Co-bleomycin; and intravenous and intraperitoneal injections produce similar T/B uptake ratios, typically between 2 and 3 at 120 minutes postinjection. In the BA 1112/WAG/Rij tumor system, local hyperthermia treatment does not seem to interfere with the subsequent accumulation of bleomycin in the tumor

1983-01-01

80

Combination therapy with radiation and bleomycin for esophageal carcinoma  

International Nuclear Information System (INIS)

A total of 204 cases with esophageal carcinoma were treated with radiation and bleomycin at Miyagiken Seijinbyo Center. 83 cases of them were classed to the palliative group and 121 to the curative one. The yearly survival rates in all cases were 41% in one, 13% in three and 8% in five years and in curative cases they were 59% in one, 22% in three and 12% in five years. The local recurrence was noted in 63% and remote metastases were observed in 43%. In comparison with the radiotherapy alone, this combination therapy was markedly superior in one to three year survival rates. Prognostic analysis was done about the following factors: 1) general conditions, 2) characteristics of carcinoma, 3) therapeutic differences. Among the factors of general conditions, the reduction rate of lymphocytes was relatively correlated with the prognosis. The cases whose reduction rate was more than 61% had poorer prognoses. Among the factors of characteristics of carcinoma, cases of Ei or Ea location indicated better prognoses, cases of less than 5 cm in length revealed good prognoses and cases of T1 or T2 showed excellent prognoses. Cases of tumorous type and a part of ulcerative type, that is, less than 5 cm in length or with shallow and smooth ulcer even if more than 5 cm, showed especially better prognosis. From the study of the factors of therapeutic differences a tumor dose of 6000 - 7000 rad was the choise in radiotherapy. As the total dose of bleomycin had no correlation with prognosis, a total of 60 to 80 mg of bleomycin was considered adequate. (J.P.N.)

1983-01-01

 
 
 
 
81

Interactions among iron(II) bleomycin, Lewis bases, and DNA.  

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The interaction of sulfur-containing ligands with complexes of Fe(II) bleomycin [Fe(II)Blm] was investigated by comparing DNA strand-scission activity with the structural characteristics of the complex. The bithiazole ring of excess Blm can form intermolecular complexes with Fe(II)Blm and with NO-Fe(II)Blm, and the bithiazole groups of CO-Fe(II)Blm interact with the metal center. This binding can be reversed by glutathione, CO-Fe(II)Blm binds to poly(dA-dT) . poly(dA-dT) via its bithiazole gr...

Antholine, W. E.; Petering, D. H.; Saryan, L. A.; Brown, C. E.

1981-01-01

82

The carbamoylmannose moiety of bleomycin mediates selective tumor cell targeting.  

Science.gov (United States)

Recently, we reported that both bleomycin (BLM) and its disaccharide, conjugated to the cyanine dye Cy5**, bound selectively to cancer cells. Thus, the disaccharide moiety alone recapitulates the tumor cell targeting properties of BLM. Here, we demonstrate that the conjugate of the BLM carbamoylmannose moiety with Cy5** showed tumor cell selective binding and also enhanced cellular uptake in most cancer cell lines. The carbamoyl functionality was required for tumor cell targeting. A dye conjugate prepared from a trivalent cluster of carbamoylmannose exhibited levels of tumor cell binding and internalization significantly greater than those of the simple carbamoylmannose-dye conjugate, consistent with a possible multivalent receptor. PMID:24811347

Bhattacharya, Chandrabali; Yu, Zhiqiang; Rishel, Michael J; Hecht, Sidney M

2014-05-27

83

"Preparation, biodistribution and stability of [65zn]bleomycin complex "  

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Bleomycin (BLM) has been labeled with various radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [65Zn] zinc chloride and its distribution and stability in normal and tumor bearing mice was determined. The complex was obtained at the pH=2 in normal saline at 90 °C in 60 minutes. Radio-TLC showed an overall radiochemical yield of 95-97% (radiochemical purity >97%). The in vitro stability of the complex was determined in mice and human plasma. Prelimi...

2004-01-01

84

Effects of ICRF-187 and L-Carnitine on bleomycin-induced lung toxicity in rats  

International Nuclear Information System (INIS)

The possible modulatory effects of ICRF-187 and L-carnitine against bleomycin-induced pulmonary toxicity in male rats were investigated. Repeated administration of bleomycin (10 mg/kg, twice weekly for 6 consecutive weeks) produced significant lung toxicity. The toxicity was manifested by significant increase in normal contents of lipid peroxide (LPO, 91.7%) reduced glutathione (GSH, 73.2%) and oxidized glutathione (GSSG, 135.4%) as well as the activity of superoxide dismutase (SOD, 222.7%). Thirty minutes prior to bleomycin treatment, other groups of rats received either ICRF-187 (95 mg/kg) or L-carnitine (500 mg/kg) adopting the same schedule of treatment as in bleomycin-treated group. L-carnitine decreased bleomycin-induced elevations in SOD activity, GSH and GSSG contents, however, it failed to suppress the increase in LPO level. On the other hand, treatment with ICRF-187 returned back all the elevated biochemical parameters induced by bleomycin to nearly normal levels. In conclusion, the results of this study showed a potential capability of ICRF-187 to mitigate the bleomycin-induced lung injury. Moreover, despite the inability of L-carnitine to change the elevated LPO content, it was able however, to decrease the elevated endogenous antioxidant parameters. (author)

2002-01-01

85

Synthesis of samarium binding bleomycin - a possible NCT radiosensitizer  

International Nuclear Information System (INIS)

Bleomycin (BLM) is a drug that has attractive features for the development of a new radiopharmaceutical, particularly with regard to neutron capture therapy (NCT) sensitized by Sm-149. It has the ability to chelate many metal ions. In vitro studies have shown that up to 78% of BLM present in a cell is accumulated inside the nucleus or in the nuclear membrane. In addition, this drug has higher affinity for tumor tissues than for normal tissues. Radioactive isotopes carried by this antibiotic would be taken preferentially to one important cellular targets DNA. Besides, BLM displays intrinsic anti-tumor activity - it is a chemotherapic antibiotic clinically used against some cancers. This study aimed to obtain bleomycin molecules bound to samarium (BLM-Sm) for NCT studies in vitro and in vivo. The binding technique employed in this work has great simplicity and low cost. Thin layer chromatography, high performance liquid chromatography, fast protein liquid chromatography and analysis by ICP-AES were applied to verify the binding molecule. ICP-AES results showed the presence of samarium in the sample peaks related to BLM-Sm. However, efficiency and stability of this bond needs to be investigated. (author)

2011-10-24

86

Synthesis of samarium binding bleomycin - a possible NCT radiosensitizer  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin (BLM) is a drug that has attractive features for the development of a new radiopharmaceutical, particularly with regard to neutron capture therapy (NCT) sensitized by Sm-149. It has the ability to chelate many metal ions. In vitro studies have shown that up to 78% of BLM present in a cell is accumulated inside the nucleus or in the nuclear membrane. In addition, this drug has higher affinity for tumor tissues than for normal tissues. Radioactive isotopes carried by this antibiotic would be taken preferentially to one important cellular targets DNA. Besides, BLM displays intrinsic anti-tumor activity - it is a chemotherapic antibiotic clinically used against some cancers. This study aimed to obtain bleomycin molecules bound to samarium (BLM-Sm) for NCT studies in vitro and in vivo. The binding technique employed in this work has great simplicity and low cost. Thin layer chromatography, high performance liquid chromatography, fast protein liquid chromatography and analysis by ICP-AES were applied to verify the binding molecule. ICP-AES results showed the presence of samarium in the sample peaks related to BLM-Sm. However, efficiency and stability of this bond needs to be investigated. (author)

Mendes, B.M., E-mail: bmm@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Mendes, T.M.; Campos, T.P.R., E-mail: campos@nuclear.ufmg.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2011-07-01

87

Experience in staging testis tumors with bleomycin cobalt 57 and present role of gallium 67 scan  

International Nuclear Information System (INIS)

A technique was developed using bleomycin and cobalt 57 to study nodal metastases in testis tumors. Comparative studies were made on 15 cases with gallium 67, lymphangiography, supraclavicular node biopsy, liver and spleen scans, chest x-ray, excretory urogram, bone survey and pathological study of surgical specimens when possible. The results with the bleomycin-cobalt 57 complex and gallium 67 were discouraging. The bleomycin-cobalt 57 study was discontinued. Pathological staging is still the most accurate of all modalities available for staging testicular malignancies

1976-01-01

88

Effects of Recombinant Activated Protein C Derived From Drotrecogin-Alpha on Bleomycin-Induced Pulmonary Fibrosis in Rats Compared with Methyl-Prednisolone  

Directory of Open Access Journals (Sweden)

Full Text Available OBJECTIVE: In this study, we aimed to test the preventive effects of intraperitoneally administered drotrecogin alpha which is derived from activated protein C (APC, on bleomycin-induced pulmonary fibrosis in rats, and to compare the effects of APC with the effects of methyl-prednisolone, a traditional therapy. MATERIAL AND METHODS: Thirty male Wistar albino rats were randomly allocated into four groups: 1. Saline alone (n=6; 2. Bleomycin+placebo (n=7; 3. Bleomycin+methyl-prednisolone (n=7; 4. Bleomycin+APC (n=10. The rats (except for the control group were given intratracheal bleomycin (2.5 mg/kg. The bleomycin+APC group was given APC (100 µg/kg/day and methyl-prednisolone treated rats were injected with 5mg/kg/day methyl-prednisolone intraperitoneally two days before the bleomycin injection; the drug was administered at the same dose for 16 days. All of the rats were killed 14 days after the intratracheal injection of bleomycin. Fibrotic changes in the lungs were demonstrated by analysing the cellular composition of bronchoalveolar lavage fluid, histological evaluation and lung hydroxyproline content.RESULTS: Fibrosis was experimentally induced in the lungs of rats using bleomycin. Fibrosis scores in the bleomycin+methyl-prednisolone and the bleomycin+APC groups were significantly lower than in the bleomycin+placebo group (p<0.05. The scores of the bleomycin+APC group and the bleomycin+methyl-prednisolone group were similar. The lung tissue hydroxyproline contents in the bleomycin+placebo and bleomycin+methyl-prednisolone groups were significantly higher than the control group (p<0.05, but the hydroxyproline content in the bleomycin+APC group was significantly lower than in the other groups (p<0.05. CONCLUSION: Drotrecogin alpha that is derived from recombinant APC has a protective effect on the pulmonary fibrosis induced by bleomycin. The protective effect seen with methyl-prednisolone is similar.

Kadir Y?ld?z

2013-04-01

89

Scintigraphic studies of malignant tumors using /sup 111/In-bleomycin  

Energy Technology Data Exchange (ETDEWEB)

A study was made of the potentialities of /sup 111/In-bleomycin in the diagnosis of lung cancer, malignant lymphomas, breast, nasopharyngeal and colonic cancer, lung metastases of synovial sarcoma. There were examined patients operated on for lung cancer to detect metastases to mediastinal lymph nodes. A group of patients with benign tumors and chronic inflammatory lung processes was examined for differential diagnosis of malignant and benign tumors. A total of 135 patients were examined using /sup 111/In-bleomycin. The results of radioisotope studies were verified by operative, morphological, X-ray and endoscopic findings. A high sensitivity has been shown for /sup 111/In-bleomycin in the diagnosis of lung and colonic cancer, malignant lymphomas. No correlation has been shown between the accumulation of /sup 111/In-bleomycin and the histologic structure of malignant tumors.

Gabuniya, R.I.; Bogdasarov, Yu.B; Zajtseva, T.I.; Lenskaya, O.P.; Shiryaev, S.V. (Akademiya Meditsinskikh Nauk SSSR, Moscow. Onkologicheskij Nauchnyj Tsentr)

1981-12-01

90

Scintigraphic studies of malignant tumors using "1"1"1In-bleomycin  

International Nuclear Information System (INIS)

A study was made of the potentialities of "1"1"1In-bleomycin in the diagnosis of lung cancer, malignant lymphomas, breast, nasopharyngeal and colonic cancer, lung metastases of synovial sarcoma. There were examined patients operated on for lung cancer to detect metastases to mediastinal lymph nodes. A group of patients with benign tumors and chronic inflammatory lung processes was examined for differential diagnosis of malignant and benign tumors. A total of 135 patients were examined using "1"1"1In-bleomycin. The results of radioisotope studies were verified by operative, morphological, X-ray and endoscopic findings. A high sensitivity has been shown for "1"1"1In-bleomycin in the diagnosis of lung and colonic cancer, malignant lymphomas. No correlation has been shown between the accumulation of "1"1"1In-bleomycin and the histologic structure of malignant tumors

1981-01-01

91

Eosinophilic pneumonia associated with bleomycin in a patient with mediastinal seminoma: a case report  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Introduction Lung toxicities resulting from the chemotherapeutic agent bleomycin encompass a variety of pathological changes, including bronchiolitis obliterans organizing pneumonia, interstitial pneumonitis and progressive interstitial fibrosis. We report a rare case of eosinophilic pneumonia associated with bleomycin. Case presentation A 44-year-old Hispanic man with a primary mediastinal seminoma complicated by superior vena cava syndrome underwent treatment with four cycles of bleomycin, etoposide and cisplatin. He had a complete positive response to the chemotherapy. However, three months after treatment he presented with shortness of breath and severe hypoxemia associated with peripheral eosinophilia. Computed tomography showed bilateral diffuse interstitial infiltrates that were refractory to antibiotic treatment. A lung biopsy showed eosinophilic pneumonia. He was subsequently treated with high-dose prednisone, resulting in a complete resolution of his symptoms and lung infiltrates. Conclusion This case illustrates that eosinophilic pneumonia may be a late sequela of bleomycin toxicity, and may respond dramatically to steroid treatment.

Chu David

2010-04-01

92

Increased and Prolonged Pulmonary Fibrosis in Surfactant Protein C-Deficient Mice Following Intratracheal Bleomycin  

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Recent reports have linked mutations in the surfactant protein C gene (SFTPC) to familial forms of pulmonary fibrosis, but it is uncertain whether deficiency of mature SP-C contributes to disease pathogenesis. In this study, we evaluated bleomycin-induced lung fibrosis in mice with genetic deletion of SFTPC. Compared with wild-type (SFTPC+/+) controls, mice lacking surfactant protein C (SFTPC?/?) had greater lung neutrophil influx at 1 week after intratracheal bleomycin, greater weight lo...

Lawson, William E.; Polosukhin, Vasiliy V.; Stathopoulos, Georgios T.; Zoia, Ornella; Han, Wei; Lane, Kirk B.; Li, Bo; Donnelly, Edwin F.; Holburn, George E.; Lewis, Kenneth G.; Collins, Robert D.; Hull, William M.; Glasser, Stephan W.; Whitsett, Jeffrey A.; Blackwell, Timothy S.

2005-01-01

93

Nitric Oxide–Dependent Activation of P53 Suppresses Bleomycin-Induced Apoptosis in the Lung  

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Chronic inflammation leading to pulmonary fibrosis develops in response to environmental pollutants, radiotherapy, or certain cancer chemotherapeutic agents. We speculated that lung injury might be mediated by p53, a proapoptotic transcription factor widely implicated in the response of cells to DNA damage. Intratracheal administration of bleomycin led to caspase-mediated DNA fragmentation characteristic of apoptosis. The effects of bleomycin were associated with translocation of p53 from the...

Davis, Darren W.; Weidner, Douglas A.; Holian, Andrij; Mcconkey, David J.

2000-01-01

94

Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy  

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Background: Though not in regular practice, intralesional (IL) bleomycin has been used for the treatment of warts since the 1970s and on the other hand, till now cryotherapy is quite regularly used to treat warts. Aim: Our aim was to assess the evidence for the efficacy of IL bleomycin, in comparison with a control group of similar sample receiving cryotherapy, in the treatment of cutaneous warts. Methods: Patients were randomized using computer-generated codes to re...

Dhar S; Rashid M; Azmm, Islam; Msi, Bhuiyan

2009-01-01

95

Preventing cleavage of Mer promotes efferocytosis and suppresses acute lung injury in bleomycin treated mice  

International Nuclear Information System (INIS)

Mer receptor tyrosine kinase (Mer) regulates macrophage activation and promotes apoptotic cell clearance. Mer activation is regulated through proteolytic cleavage of the extracellular domain. To determine if membrane-bound Mer is cleaved during bleomycin-induced lung injury, and, if so, how preventing the cleavage of Mer enhances apoptotic cell uptake and down-regulates pulmonary immune responses. During bleomycin-induced acute lung injury in mice, membrane-bound Mer expression decreased, but production of soluble Mer and activity as well as expression of disintegrin and metalloproteinase 17 (ADAM17) were enhanced . Treatment with the ADAM inhibitor TAPI-0 restored Mer expression and diminished soluble Mer production. Furthermore, TAPI-0 increased Mer activation in alveolar macrophages and lung tissue resulting in enhanced apoptotic cell clearance in vivo and ex vivo by alveolar macrophages. Suppression of bleomycin-induced pro-inflammatory mediators, but enhancement of hepatocyte growth factor induction were seen after TAPI-0 treatment. Additional bleomycin-induced inflammatory responses reduced by TAPI-0 treatment included inflammatory cell recruitment into the lungs, levels of total protein and lactate dehydrogenase activity in bronchoalveolar lavage fluid, as well as caspase-3 and caspase-9 activity and alveolar epithelial cell apoptosis in lung tissue. Importantly, the effects of TAPI-0 on bleomycin-induced inflammation and apoptosis were reversed by coadministration of specific Mer-neutralizing antibodies. These findings suggest that restored membrane-bound Mer expression by TAPI-0 treatment may help resolve lung inflammation and apoptosis after bleomycin treatment. -- Highlights: ?Mer expression is restored by TAPI-0 treatment in bleomycin-stimulated lung. ?Mer signaling is enhanced by TAPI-0 treatment in bleomycin-stimulated lung. ?TAPI-0 enhances efferocytosis and promotes resolution of lung injury.

2012-08-15

96

The Effect of Class II Transactivator Mutations on Bleomycin-Induced Lung Inflammation and Fibrosis  

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IFN-? expression increases during the inflammatory response after bleomycin injury in mice. IFN-? deficiency attenuates lung inflammation and fibrosis. Because IFN-? stimulates class II transactivator (CIITA) expression, which activates major histocompatibility class (MHC) II and represses collagen expression, it was hypothesized that CIITA mediates IFN-? action after bleomycin injury. To test this hypothesis, two CIITA mouse lines, one carrying a mutation of the leucine-rich region of CI...

Xu, Yong; Luchsinger, Larry; Lucey, Edgar C.; Smith, Barbara D.

2011-01-01

97

Bleomycin Induces Molecular Changes Directly Relevant to Idiopathic Pulmonary Fibrosis: A Model for “Active” Disease  

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The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show fo...

Peng, Ruoqi; Sridhar, Sriram; Tyagi, Gaurav; Phillips, Jonathan E.; Garrido, Rosario; Harris, Paul; Burns, Lisa; Renteria, Lorena; Woods, John; Chen, Leena; Allard, John; Ravindran, Palanikumar; Bitter, Hans; Liang, Zhenmin; Hogaboam, Cory M.

2013-01-01

98

Bleomycin-induced DNA repair by Saccharomyces cerevisiae ATP-dependent polydeoxyribonucleotide ligase  

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In contrast to ligase-deficient (cdc9) Saccharomyces cerevisiae, which did not rejoin bleomycin-induced DNA breaks, ligase-proficient (CDC9) yeast cells eliminated approximately 90% of DNA breaks within 90 to 120 min after treatment. Experimental conditions restricted enzymatic removal of the unusual 3{prime}-phosphoglycolate terminal in DNA cleaved by bleomycin and involved doses producing equivalent numbers of DNA breaks or doses producing equivalent killing.

Moore, C.W. (Univ. of Rochester School of Medicine and Dentistry, NY (USA))

1988-10-01

99

Production and biological studies of 111In-bleomycin for diagnosis/ therapy purposes  

International Nuclear Information System (INIS)

Fe mycin (Bleomycin) is an anti- neoplastic agent which is used in the treatment of squamous cell carcinoma, Hodgkin's lymphoma, and testicles carcinoma. Due to the progress in application and production of SPECT radioisotopes in nuclear medicine, bleomycin was labeled with In-111 which was well accepted in clinics, In mid 70' s un stability of 111 In-Bleomycin made scientists to ignore this agent as an imaging tool, but in 1984 a new stable complex was prepared and used in clinics. In order to obtain the best labeling reaction conditions, the complex formation was optimized for P H, temperature, time,and amount of bleomycin using I TLC and R TLC methods. The labeled compound was injected to normal rats (weighing 150-200 g). Autopsy on the rats at various time intervals after injection and the data was obtained and compared with In111 chloride in normal rats. The radio- labeling method, utilizes no chromatographic purification of desired compound, due to exact optimization of reaction conditions.Total labeling and formulation of 111In-Bleomycin took about 30 Min, with a yield of 99.8%. 111In-Bleomycin was examined by various chromatographic system and shown to have a consistent final specific activity in excess of 1.39 Ci/m mole (limit of detection). The radio-labeled complex was stable m aqueous solutions at leas for 24 hours species followed by filtration through a 0.22 u filter

2002-10-19

100

Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy  

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Full Text Available Background: Though not in regular practice, intralesional (IL bleomycin has been used for the treatment of warts since the 1970s and on the other hand, till now cryotherapy is quite regularly used to treat warts. Aim: Our aim was to assess the evidence for the efficacy of IL bleomycin, in comparison with a control group of similar sample receiving cryotherapy, in the treatment of cutaneous warts. Methods: Patients were randomized using computer-generated codes to receive either cryotherapy (double freeze-thaw cycle or IL bleomycin (0.1% solution with concurrent anesthesia for a maximum of four treatments 3 weeks apart and a maximum of five warts treated in each visit for both groups. Patients had their warts measured at base-line and with each return visit including a post treatment follow-up that was 8 weeks apart from last treatment taken. Results: Of the 73 patients completing the study, 39 (53% were treated with IL bleomycin and 34 (47% were treated with cryotherapy. Out of 155 treated warts, 87 (56% were treated with IL beomycin and 68 (44% were treated with cryotherapy. The clearance rates in context of number of patients and number of warts were 94.9% and 97% for bleomycin and 76.5% and 82% for cryotherapy respectively ( P < 0.05 by x 2 analysis and RR = 7.67. Conclusion: IL bleomycin injection was significantly more effective than cryotherapy for treatment of cutaneous wart.

Dhar S

2009-01-01

 
 
 
 
101

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Full Text Available AbstractBackground and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.Methods: Silymarin (50 mg/kg, i.p. was administered two days before the bleomycin instillation (3 U/kg and throughout the test interval in mice. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and histological analysis of pathological lung changes. Data were evaluated by one-way ANOVA and Dunnett analysis. P<0.05 was considered as significant. Results: Pretreatment with Silymarin significantly (P<0.05 prevented the increase in lung collagen content and also partially inhibited the histologic changes induced by bleomycin. The wet lung weight in silymarin group was similar to that of control group and significantly lower than bleomycin group (P<0.001. Conclusion: The results of this study indicate that silymarin may prevent the collagen deposition and inflammation and may be protective in fibrogenic effects of bleomycin on lung.Keywords: Silymarin; Bleomycin; Pulmonary Fibrosis; Hydroxyproline.

L. Safaeian

2009-08-01

102

Differential expression of extracellular matrix remodeling genes in a murine model of bleomycin-induced pulmonary fibrosis.  

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Exposure to the chemotherapeutic drug bleomycin leads to pulmonary fibrosis in humans and has been widely used in animal models of the disease. Using C57BL/6 bleomycin-sensitive mice, pulmonary fibrosis was induced by multiple intraperitoneal injections of the drug. An increase in the relative amounts of steady-state alpha1(I) procollagen, alpha1(III) procollagen, and fibronectin mRNA as well as histopathological evidence of fibrosis was observed. The effect of bleomycin on the expression of ...

Swiderski, R. E.; Dencoff, J. E.; Floerchinger, C. S.; Shapiro, S. D.; Hunninghake, G. W.

1998-01-01

103

Tumor affinity and DNA interactions of 57Co-bleomycin  

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Cobalt-57-bleomycin (BLM) has been proven to be the most stable and useful tumor-diagnostic agent among several radiolabelled BLMs. However, the considerably long half life of 57Co causes troubles in handling and preclude its extensive uses. In our previous work, BLM was proved to form two geometrical isomers, in chelating with Co. In this paper, we compared the tumor affinity of two isomers, to make an improvement of this drug's merit. We investigated biodistribution in tumor-bearing mice and DNA binding properties by fluorescence quenching technique and DNA melting study. A comparison of the data obtained suggests that isomerism affects the tumor affinity of the drug. Both tumor accumulation in tumor-bearing mice and stability of DNA binding of type I isomer were higher than those of type II. If a certain suitable radionuclide is inserted into cold Co-BLM type I isomer, this agent will be a greatly useful tumor-imaging radiopharmaceutical. (author)

1982-01-01

104

"Preparation, biodistribution and stability of [65zn]bleomycin complex "  

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Full Text Available Bleomycin (BLM has been labeled with various radioisotopes and widely used in therapy and diagnosis. In this study BLM was labeled with [65Zn] zinc chloride and its distribution and stability in normal and tumor bearing mice was determined. The complex was obtained at the pH=2 in normal saline at 90 °C in 60 minutes. Radio-TLC showed an overall radiochemical yield of 95-97% (radiochemical purity >97%. The in vitro stability of the complex was determined in mice and human plasma. Preliminary studies were performed to determine distribution of [65Zn]BLM in normal and tumor bearing mice on the basis of these results. [65Zn]BLM may be used in therapeutic studies due to its suitable physico-chemical properties.

Amir Reza Jalilian

2004-08-01

105

In-vitro and in-vivo characterization of ruthenium-bleomycin compared to cobalt- and copper-bleomycin  

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Bleomycin (BLM) has undergone extensive investigation both as a cancer chemotherapeutic agent, and as a carrier for radionuclides for tumor imaging. The available methods or the radionuclides used, however, have had limited effectiveness. Although labeling of BLM with 103Ru has been reported earlier, we carried out a study to develop a more reproducible method of labeling particularly for use with Brookhaven Linac Isotope Producer produced 97Ru. Ruthenium-97 has favorable physical properties that make it ideal for imaging applications: decay by electron capture; ? 216 keV, 85%; t/sub 1/2/ 2.9 d. A novel method based on the reduction of Ru3+ to Ru2+ using stannous chloride was investigated for labeling BLM with 97Ru and/or 103Ru. In-vitro and in vivo comparisons of the product(s) with 57Co and 67Cu-labeled BLM were also carried out. 4 refs., 3 tabs

1986-06-22

106

A rat model of pulmonary fibrosis induced by infusing bleomycin quickly through tracheal intubation  

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Full Text Available Objective: To study the approach for developing a rat model of pulmonary fibrosis induced by bleomycin (BLM.Method: Different doses (7, 6, 5, 3.4, 2, 1 mg/kg of bleomycin A5-saline were infused into the rats' lung in bleomycin-treated group through tracheal intubation, and rats in sham-operated group were infused with same volume of saline. The living state and lung pathology of the rats were observed. The author deeply studied the condition of the rats in 1 mg/kg bleomycin-treated group, and the changes of body weight and lung pathology were observed. Lung quotient, the content of transforming growth factor ?1?TGF-?1?and platelet-derived growth factor (PDGF in serum were measured on the 14th, 28th and 45th day of the experiment.Results: The study demonstrated that infusing large doses of bleomycin A5 quickly through tracheal intubation had a high mortality, and infusing 1 mg/kg quickly could successfully develop an animal model of pulmonary fibrosis. Compared with the sham-operated group, fibrosis was appeared obviously in the rats' lung in 1 mg/kg bleomycin A5-treated group after 14 days of experiment, diffuse fibrosis was appeared after 28 days of experiment, and the fibrosis became more severe after 45 days of experiment. The body weight of the rats in bleomycin-treated group was declined after 3, 7 and 14 days of experiment as compared with the sham-operated group (P0.05. Lung quotient was increased 14, 28 and 45 days after the experiment (P<0.01, the level of serum TGF-?1 began to increase since 28 days after the experiment (P<0.05, P<0.01, and the level of serum PDGF also increased gradually 45 days after the experiment (P<0.05. And the mortality rate of 1 mg/kg bleomycin A5-treated group was lower than those of the other doses of bleomycin A5-treated groups.Conclusion: A rat model of pulmonary fibrosis can be duplicated successfully by infusing 1 mg/kg bleomycin A5 quickly through tracheal intubation.

Wei ZHANG

2008-01-01

107

The astrophysical reactions "1"2C(?,?)"1"6O and "7Be(p,?)"8B and Coulomb dissociation experiments  

International Nuclear Information System (INIS)

The use of the Coulomb dissociation method to obtain the cross sections for the radiative capture reactions "1"2C(?, ?)"1"6O and "7Be(p, ?)"8B is investigated. The contribution of the nuclear interaction to the breakup is included. Due to the low binding of the proton in "8B the second reaction is dominated by Coulomb breakup. The effects of Coulomb reacceleration of the fragments and of the excitation of states in the fragments is also studied. Ideal kinematical conditions for the experiments are investigated. (orig.)

1993-01-01

108

Study of the D(p,?+)T and 9Be(p,?+)10Be from 400 to 800MeV  

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Pion production on CD2 and 9Be targets has been observed using the high resolution, energy loss, spectrometer SPES I. Differential cross sections for the D(p,?+) reaction have been determined at 410, 605 and 809MeV and for the 9Be(p,?+) reaction at 410 and 605MeV. The 3.37MeV (2+) state in 10Be is populated preferentially, but a significant part of the transition strength seems to populate the ground state and the higher lying multiplets at about 6.1MeV, 7.4MeV and 9.4MeV

109

Static and dynamic mechanics of the murine lung after intratracheal bleomycin  

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Full Text Available Abstract Background Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure. Methods Single intratracheal injections of saline (50 ?L or bleomycin (2 mg/Kg in 50 ?L saline were administered to C57BL/6 (n = 40 and Balb/c (n = 32 mice. Injury/fibrosis score, tissue volume density (TVD, collagen content, airway resistance (RN, tissue damping (G and elastance coefficient (H, hysteresivity (?, and area of pressure-volume curve (PV-A were determined after 7 and 21 days (inflammation and fibrosis stage, respectively. Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests. Results Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls. Conclusions Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.

Papiris Spyridon

2011-05-01

110

Bleomycin as carrier substance for sup(99m)technetium in tumour diagnosis  

International Nuclear Information System (INIS)

sup(99m)Tc-Bleomycin is a promising tool for scintigraphic imaging of some types of malignant tumours. The rapid decay of sup(99m)Tc, together with a high affinity of bleomycin for certain histologically-defined tumours recommends its use in humans. Moreover, by using high specific activities of bleomycin, no toxic effects are to be expected. At 00C, the chelate of sup(99m)Tc and bleomycin is stable and its storage or transport are recommended at this temperature. Following the i.v. injection of rats with sup(99m)Tc-bleomycin, a high specific activity is found in the liver, spleen, lungs and skin. In view of its excretion by the kidneys an extremely high activity is found in the urogenial system. Scintigraphic imaging of lymph nodes in a case of Hodgkin's disease, of an embryonal carcinoma, of a thyroid carcinoma, of an astrocytoma and of a solid carcinoma was obtained in patients investigated by this method. (author)

1975-01-01

111

Study of the cellular uptake and distribution of 57cobalt bleomycin in Ehrlich ascites tumor cells  

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We investigated the dependence of the cellular uptake of 57 cobalt-bleomycin on the exposure time and on the dose. In addition we observed the influences due to the incubation temperature, to the growth phase of the tumor cells and due to the composition of the suspensory medium. In supplementary experiments we investigated the binding of the labelled cytostatic agent to erythrocytes, its adsorption to broken Ehrlich ascites tumor cells and the 57 cobalt-bleomycin outflow from pre-loaded intact Ehrlich ascites tumor cells. The 57 cobalt-bleomycin uptake of intact Ehrlich ascites tumor cells is determined by characteristic kinetics. Moreover, the erythrocytes and injured Ehrlich ascites tumor cells show a qualitatively similar graph of the 57 cobalt-bleomycin binding, which can clearly be distinguished from the kinetics found with intact Ehrlich ascites tumor cells. The uptake of this cytostatic agent depends on an unequivocal time-dose-temperature relationship. The transport mechanism of the 57 cobalt-bleomycin uptake was considered as endocytosis. An endocytosis-stimulating inducer could not be detected. However, we obtained indications that the cell-bound cytostatic agent is taken up in two compartments: on the cellular surface and in the interior of the cell. (orig./MG)

1980-01-01

112

Experience and results in the treatment of ORL tumours with bleomycin and radiotherapy  

International Nuclear Information System (INIS)

Since 1974 Bleomycin has been applied in our hospital in combination with radiotherapy to treat advanced ORL-carcinomas. In a 1st phase (X.74-VII.77), Bleomycin (6D 60 mg) was applied to 20 patients by infusion before starting radiotherapy. In a second group of patients, from II.78, the principle of simultaneous treatment was adhered to, 30-60 min. prior to starting radiotherapy max. 5 mg Bleomycin i.m.. For 10 patients, treatment was finished at least 2 months ago. The rate of at least partial clinical remission 70% (45% complete remission), in the 2nd group it was 100% (50% complete remission). In fixed lymphomas, the rate of clinically total tumour reduction dropped to 25%; in NO-2-findings, however, it was 70%. The substantial characteristic of the combined treatment with Bleomycin was the spontaneous easing of the pain, especially in the group of the simultaneously treated patients. An early fibrinous mucositis cannot be avoided. The theories of the differing techniques of application were explained. Finally, an attempt is made to define the indications for Bleomycin in treating ORL-tumours. After finishing this paper, the number of the patients treated according to scheme 2 increased to more than 40. (orig./MG) 891 MG/orig. 892 RDG

1978-10-21

113

Characterization of the association of radiolabeled bleomycin A2 with HeLa cells  

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The association of (/sup 3/H)bleomycin A2 and Cu(II):(/sup 3/H)bleomycin A2 with HeLa cells has been characterized. Under the conditions of our experiments, approximately 0.1% of the total drug in the medium associates with HeLa cells. Both forms of the drug bind to HeLa cells in a specific and saturable manner, with a Km of 20 microM and a Vmax of 2.5 pmol/min/10(6) cells. Scatchard analysis of the specific binding data demonstrates a single set of high-affinity binding sites. Cytotoxic activities of both forms of the drug are similar, with a 50% lethal dose of 0.5 microM at 48 hr. The specific binding in HeLa cells of either the labeled metal-free drug or its copper complex is reversible by a 100-fold excess of either unlabeled drug. Interaction of the drug with cells is temperature sensitive but is unaffected by metabolic poisons, suggesting that this process is not energy dependent. Isolation of DNA from HeLa cells incubated with the drug indicates that 1 mol of either (/sup 3/H)bleomycin A2 or Cu(II):(/sup 3/H)bleomycin A2 binds per 10(8) nucleotides. Further studies with the radiolabeled drug are required to define precisely the mechanisms involved in bleomycin uptake and compartmentalization within the cell.

Roy, S.N.; Horwitz, S.B.

1984-04-01

114

Labelling of bleomycin with cobalt-57, indium-111, technetium-99m, mercury-197, lead-203, and copper-67  

International Nuclear Information System (INIS)

The radiochemical purity of the cobalt-57 complex of bleomycin could be enhanced by adjusting the pH of the final product to a value between 5 and 6. This radiopharmaceutical appeared to have better tumor visualizing properties compared to the not neutralized preparation. The clinical use of the cobalt-57 bleomycin complex is however limited by the long physical half-life of the label, causing a risk of radioactive contamination. It appeared to be possible to label bleomycin with radioactive cations (111In3+, sup(99m)Tc4+, 197Hg2+ and 67Cu2+) having suitable gamma ray energies and short half-lifes. These bleomycin complexes showed a high radiochemical purity judged by their behaviour on thin layer chromatography, paper chromatography, and electrophoresis, but their application as tumor visualizing radiopharmaceutical turned out to be disappointing compared with cobalt-57 bleomycin. (orig.)

1976-04-01

115

The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells  

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Bleomycin, a radiomimetic glycopeptide, inhibits de novo DNA synthesis in ataxia telangiectasia lymphoblastoid B cells to a markedly lesser extent than in normal and xeroderma pigmentosum lymphoid cells. This observation is similar to that following ionizing radiation; however, the effect is slower following the chemical treatment. Recovery of the normal cells occurs 15-18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24-hour observation period. Similar differences were not observed following treatment with mitomycin C, a bifunctional alkylating agent, indicating a specific effect of bleomycin on DNA synthesis in ataxia telangiectasia cells. Following bleomycin treatment and preincubation with hydroxyurea, residual DNA synthesis in ataxia telangiectasia cells was similar to that in both normal and xeroderma pigmentosum lymphoid lines, suggesting that the capacity to repair the induced DNA lesion is present.

Cohen, M.M.; Simpson, S.J.

1982-01-01

116

The effect of bleomycin on DNA synthesis in ataxia telangiectasia lymphoid cells  

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Bleomycin, a radiomimetic glycopeptide, inhibits de novo DNA synthesis in ataxia telangiectasia lymphoblastoid B cells to a markedly lesser extent than in normal and xeroderma pigmentosum lymphoid cells. This observation is similar to that following ionizing radiation; however, the effect is slower following the chemical treatment. Recovery of the normal cells occurs 15-18 hours after treatment, whereas the ataxia telangiectasia lines do not attain normal levels of DNA synthesis during the entire 24-hour observation period. Similar differences were not observed following treatment with mitomycin C, a bifunctional alkylating agent, indicating a specific effect of bleomycin on DNA synthesis in ataxia telangiectasia cells. Following bleomycin treatment and preincubation with hydroxyurea, residual DNA synthesis in ataxia telangiectasia cells was similar to that in both normal and xeroderma pigmentosum lymphoid lines, suggesting that the capacity to repair the induced DNA lesion is present

1982-01-01

117

Percutaneous sclerotherapy of juvenile nasopharyngeal angiofibroma using fibrin glue combined with OK-432 and bleomycin.  

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The purpose of this study was to determine the appropriate conditions for percutaneous sclerotherapy of juvenile nasopharyngeal angiofibroma using fibrin glue combined with OK-432 and bleomycin. Three patients with juvenile nasopharyngeal angiofibroma were treated with an injection of fibrin glue combined with OK-432 and bleomycin. No major complications occurred in any of the patients. The follow-up period ranged from 12 to 14 months. The following outcomes were obtained: one lesion was completely involuted and two lesions were mostly involuted. All of the patients had normal liver and kidney function. Additionally, none of the patients presented with hematologic toxic effects or signs of pulmonary involvement. Percutaneous sclerotherapy using fibrin glue combined with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for juvenile nasopharyngeal angiofibroma. PMID:20189660

Chen, Wei-liang; Huang, Zhi-quan; Li, Jin-song; Chai, Qiang; Zhang, Da-ming

2010-04-01

118

Microscopic study of the 7Li(n,?)8Li and 7Be(p,?)8B reactions in a multiconfiguration three-cluster model  

International Nuclear Information System (INIS)

The three-cluster generator coordinate method is applied to the 7Li(n,?)8Li and 7Be(p,?)8B capture reactions. The 8B (or 8Li) nucleus is defined by a mixing of (?+3He)+p and (?+p)+3He (or mirror) configurations. We investigate the sensitivity of different observables with respect to the nucleon-nucleon interaction by considering four different Volkov forces. For all of them, the model fairly reproduces most of the experimentally known spectroscopic properties of the 8B and 8Li mirror nuclei. Recent measurements of the quadrupole moments are well explained without a halo structure. The 7Li(n,?)8Li cross section supports the data of Imhof et al. rather than those of Wiescher et al. At zero energy, the 7Be(p,?)8B astrophysical S-factors slightly depend on the nucleon-nucleon interaction. They are consistent with the currently accepted value, but contradict lower estimates. (orig.)

1994-01-17

119

Studies on increase of intracellular reactive oxygen species and oxidative DNA damage in 60Co ? ray irradiated BEP2D cells  

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HPV-16 immortalized human bronchial epithelial cells (BEP2D) were irradiated by 60Co gamma rays. 2',7'-dichlorofluorescein and ethidium bromide, fluorescent products of the membrane-permeable dyes 2',7'-dichlorofluorescein diacetate and hydro-ethine, respectively, were used to monitor the intracellular production of hydrogen peroxides (H2O2) and superoxide anions (O2.-) respectively, by flow cytometry. 8-hydroxy-deoxy-gunosine (OH8dG), a production of oxidative DNA damage, was examined with HPLC-ECD from extracted DNA. The results shoed that the ROS productions and DNA adduct OH8dG in 60Co gamma rays irradiated BEP2D cells increased remarkably, and revealed better dose-response correlation. Further analysis indicated the positive correlation between intracellular ROS and content of OH8dG induced by 60Co gamma rays. Therefore, the effects of radiation on cell were involved increase of intracellular ROS and its production of oxidative DNA damage

2001-11-01

120

Protective role of andrographolide in bleomycin-induced pulmonary fibrosis in mice.  

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Idiopathic pulmonary fibrosis (IPF) is a chronic devastating disease with poor prognosis. Multiple pathological processes, including inflammation, epithelial mesenchymal transition (EMT), apoptosis, and oxidative stress, are involved in the pathogenesis of IPF. Recent findings suggested that nuclear factor-?B (NF-?B) is constitutively activated in IPF and acts as a central regulator in the pathogenesis of IPF. The aim of our study was to reveal the value of andrographolide on bleomycin-induced inflammation and fibrosis in mice. The indicated dosages of andrographolide were administered in mice with bleomycin-induced pulmonary fibrosis. On day 21, cell counts of total cells, macrophages, neutrophils and lymphocytes, alone with TNF-? in bronchoalveolar lavage fluid (BALF) were measured. HE staining and Masson's trichrome (MT) staining were used to observe the histological alterations of lungs. The Ashcroft score and hydroxyproline content of lungs were also measured. TGF-?1 and ?-SMA mRNA and protein were analyzed. Activation of NF-?B was determined by western blotting and electrophoretic mobility shift assay (EMSA). On day 21 after bleomycin stimulation, andrographolide dose-dependently inhibited the inflammatory cells and TNF-? in BALF. Meanwhile, our data demonstrated that the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung were reduced by andrographolide administration. Furthermore, andrographloide suppressed TGF-?1 and ?-SMA mRNA and protein expression in bleomycin-induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose-dependently inhibited the ratio of phospho-NF-?B p65/total NF-?B p65 and NF-?B p65 DNA binding activities. Our findings indicate that andrographolide compromised bleomycin-induced pulmonary inflammation and fibrosis possibly through inactivation of NF-?B. Andrographolide holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis. PMID:24300094

Zhu, Tao; Zhang, Wei; Xiao, Min; Chen, Hongying; Jin, Hong

2013-01-01

 
 
 
 
121

Heat shock protein 70 protects against bleomycin-induced pulmonary fibrosis in mice.  

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Idiopathic pulmonary fibrosis (IPF) involves infiltration of leucocytes, pulmonary injury, fibrosis and resulting pulmonary dysfunction. Myofibroblasts and transforming growth factor (TGF)-beta1 have been suggested to play a major role in the pathology and the myofibroblasts are derived from both lung epithelial cells through epithelial-mesenchymal transition (EMT) and activation of lung fibroblasts. Heat shock protein 70 (HSP70) confers protection against various stressors and has the anti-inflammatory activity. In this study, we examined the effect of expression of HSP70 on bleomycin-induced pulmonary fibrosis in mice, a tentative animal model of IPF. Bleomycin-induced pulmonary injury and inflammatory response were ameliorated in transgenic mice overexpressing HSP70 compared to wild-type mice, even though bleomycin-induced pulmonary fibrosis and dysfunction were also suppressed in the transgenic mice. The production of TGF-beta1 and expression of pro-inflammatory cytokines was lower in cells from the transgenic mice than wild-type mice after the administration of bleomycin. In vitro, the suppression of HSP70 expression stimulated TGF-beta1-induced EMT-like phenotypes of epithelial cells but did not affect the TGF-beta1-dependent activation of fibroblasts. Orally administered geranylgeranylacetone (GGA), a clinically used drug with HSP-inducing activity, conferred protection against bleomycin-induced pulmonary injury, as well as against the inflammatory response, fibrosis and dysfunction. These results suggest that HSP70 plays a protective role against bleomycin-induced pulmonary injury, inflammation, fibrosis and dysfunction through cytoprotective effects and by inhibiting the production of TGF-beta1, TGF-beta1-dependent EMT of epithelial cells and expression of pro-inflammatory cytokines. Results also suggest that HSP70-inducing drugs, such as GGA, could be beneficial in the prophylaxis of IPF. PMID:20513440

Tanaka, Ken-Ichiro; Tanaka, Yuta; Namba, Takushi; Azuma, Arata; Mizushima, Tohru

2010-09-15

122

Pharmacological inhibition of leukotrienes in an animal model of bleomycin-induced acute lung injury  

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Full Text Available Abstract Leukotrienes are increased locally in idiopathic pulmonary fibrosis. Furthermore, a role for these arachidonic acid metabolites has been thoroughly characterized in the animal bleomycin model of lung fibrosis by using different gene knock-out settings. We investigated the efficacy of pharmacological inhibition of leukotrienes activity in the development of bleomycin-induced lung injury by comparing the responses in wild-type mice with mice treated with zileuton, a 5-lipoxygenase inhibitor and MK-571, a cys-leukotrienes receptor antagonist. Mice were subjected to intra-tracheal administration of bleomycin or saline and were assigned to receive either MK-571 at 1 mg/Kg or zileuton at 50 mg/Kg daily. One week after bleomycin administration, BAL cell counts, lung histology with van Gieson for collagen staining and immunohistochemical analysis for myeloperoxidase, IL-1 and TNF-? were performed. Following bleomycin administration both MK-571 and zileuton treated mice exhibited a reduced degree of lung damage and inflammation when compared to WT mice as shown by the reduction of:(i loss of body weight, (ii mortality rate, (iii lung infiltration by neutrophils (myeloperoxidase activity, BAL total and differential cell counts, (iv lung edema, (v histological evidence of lung injury and collagen deposition, (vi lung myeloperoxidase, IL-1 and TNF-? staining. This is the first study showing that the pharmacological inhibition of leukotrienes activity attenuates bleomycin-induced lung injury in mice. Given our results as well as those coming from genetic studies, it might be considered meaningful to trial this drug class in the treatment of pulmonary fibrosis, a disease that still represents a major challenge to medical treatment.

Crimi Nunzio

2006-11-01

123

Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic devastating disease with poor prognosis. Multiple pathological processes, including inflammation, epithelial mesenchymal transition (EMT, apoptosis, and oxidative stress, are involved in the pathogenesis of IPF. Recent findings suggested that nuclear factor-?B (NF-?B is constitutively activated in IPF and acts as a central regulator in the pathogenesis of IPF. The aim of our study was to reveal the value of andrographolide on bleomycin-induced inflammation and fibrosis in mice. The indicated dosages of andrographolide were administered in mice with bleomycin-induced pulmonary fibrosis. On day 21, cell counts of total cells, macrophages, neutrophils and lymphocytes, alone with TNF-? in bronchoalveolar lavage fluid (BALF were measured. HE staining and Masson’s trichrome (MT staining were used to observe the histological alterations of lungs. The Ashcroft score and hydroxyproline content of lungs were also measured. TGF-?1 and ?-SMA mRNA and protein were analyzed. Activation of NF-?B was determined by western blotting and electrophoretic mobility shift assay (EMSA. On day 21 after bleomycin stimulation, andrographolide dose-dependently inhibited the inflammatory cells and TNF-? in BALF. Meanwhile, our data demonstrated that the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung were reduced by andrographolide administration. Furthermore, andrographloide suppressed TGF-?1 and ?-SMA mRNA and protein expression in bleomycin-induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose-dependently inhibited the ratio of phospho-NF-?B p65/total NF-?B p65 and NF-?B p65 DNA binding activities. Our findings indicate that andrographolide compromised bleomycin-induced pulmonary inflammation and fibrosis possibly through inactivation of NF-?B. Andrographolide holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis.

Tao Zhu

2013-12-01

124

Problems in the differentiation of lung infiltrates following bleomycin therapy from metastases  

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Sixty patients with malignant testicular tumours were treated with bleomycin according to the Einhorn regime. Following treatment, pulmonary infiltrates were seen on the chest X-ray of three patients and the CT of six patients. Altogether 24 infiltrates resembling metastases were seen in five patients. Five round foci were combined with infiltrates in other parts of the lung. Regression of the infiltrates after stopping bleomycin, negative tumour markers, the timing of the development of the infiltrates and the regression of the infiltrates in three patients without treatment make it extremely unlikely that the appearances were due to metastases. (orig.)

1984-10-01

125

Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study  

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Full Text Available Human peripheral blood lymphocytes from 10 patients with familial adenomatous polyposis (FAP showed a significantly higher incidence of chromatid breaks when compared to cells from 10 normal individuals, after exposure to bleomycin (BLM during the G2 phase. However, no significant increase in bleomycin sensitivity was observed in lymphocytes from 10 patients with sporadic adenomatous polyps (AP vs. 10 normal individuals (P = 0.67. Individuals that exhibited an average number of chromatid breaks per cell higher than 0.80 were considered sensitive to the drug. No control showed susceptibility to BLM, as compared to 3 out of 20 patients.

Sales Magaly M.

1999-01-01

126

Dynamic Distribution of 67Ga-Bleomycin Complex and Carrier Free 67Gallium in Normal Mice  

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This study reports the labeling of Gallium-Bleomycin (67Ga-BLM) complex as a radiopharmaceutical and optimization of its labeling conditions; pH, reaction time, temperature, concentration of bleomycin and its biodistribution in normal Bulb C mice. The biodistribution of the complex was compared with 67Ga-Cl3 in 11 selected organs including blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content, and bladder at five selected times of 1, 2, 4, 24 and 48 hours after injecti...

2002-01-01

127

57Co-bleomycin and 67Ga-citrate in detecting and staging lung cancer.  

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In the investigation of suspected lung cancer bleomycin labelled with cobalt-57 and gallium-67 labelled with citrate are currently used to detect the primary tumour and to establish the presence of metastases in the lung hilum and mediastinum. A comparative study of these radio-pharmaceuticals was performed in 63 patients with proved lung cancer. 57Co-bleomycin showed the primary tumour in 58 patients (92%) and 67 Ga-citrate in 34 (54%) (p less than 0.01). The average tumour-to-lung ratio was...

1983-01-01

128

_5_7Co-bleomycin and _6_7Ga-citrate in detecting and staging lung cancer  

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In the investigation of suspected lung cancer, bleomycin labelled with cobalt-57, and gallium-67 labelled with citrate are currently used to detect the primary tumour and to establish the presence of metastases in the lung hilum and mediastinum. A comparative study of these radiopharmaceuticals was performed in 63 patients with proved lung cancer. _5_7Co-bleomycin showed the primary tumour in 58 patients (92%) and _6_7Ga-citrate in 34 (54%) (p < 0.01). The average tumour-to-lung ratio was 3.4 with _5_7Co-bleomycin and 1.5 with _6_7Ga-citrate. Proved metastases in the hilum or the mediastinum were visualised with _5_7Co-bleomycin scintigraphy in 16 out of 18 patients (89%) and with _6_7Ga-citrate scintigraphy in only eight (45%) (p < 0.01). These results indicate that _5_7Co-bleomycin scintigraphy is more suitable for detecting and staging lung cancer than is _6_7Ga-citrate. _5_7Co-bleomycin is valuable in the detection of peripheral lesions, in which a pathological diagnosis is difficult to achieve, since a positive scintigram indicates malignancy. When _5_7Co-bleomycin scintigraphy suggests hilar or mediastinal metastases mediastinoscopy should be carried out; but when no metastases are apparent it is reasonable to proceed directly to thoracotomy without mediastinoscopy. (author)

1983-01-01

129

A highly sensitive resonance Rayleigh scattering method for the determination of bleomycinA5 and bleomycinA2 with some halofluorescein dyes.  

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In a weak acidic medium, bleomycinA(5) (BLMA(5)) and bleomycinA(2) (BLMA(2)) can react with halofluorescein dyes such as erythrosine (Ery), eosin Y (EY), eosin B (EB) and Rose Bengal (RB) by virtue of electrostatic attraction and hydrophobic force to form ion-association complexes, which can result in the large-scale enhancement of resonance Rayleigh scattering (RRS) and the appearance of new RRS spectra. The increments of scattering intensity (Delta I) were directly proportional to the concentrations of bleomycin (BLM) in certain ranges. The detection limits for BLMA(5) and BLMA(2) ranged from 0.017 to 0.062 microg ml(-1). The Ery system had the highest sensitivity and its detection limit (3sigma) was 0.017 microg ml(-1) for BLMA(5) and 0.018 microg ml(-1) for BLMA(2), respectively. Using Ery as a RRS probe, a new highly sensitive method for the determination of BLM anticancer drugs has been developed. It was applied in the determination of BLMA(5) and BLMA(2) in serum and urine samples. The recovery was from 99.0% to 103.0%. In this work, the RRS spectral characteristics of the binding products and the optimum conditions of the reaction were investigated. The mechanism of ion-association reaction and the reasons of enhancement of resonance light scattering were discussed. PMID:17174057

Liu, Jiangtao; Liu, Zhongfang; Hu, Xiaoli; Kong, Ling; Liu, Shaopu

2007-03-12

130

Comparison of gamma radiation and radiomimmetic chemical, bleomycin in leukocytes from certain genetic disorders  

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Full text: To compare the frequency and distribution pattern of bleomycin and gamma radiation induced chromosomal aberrations in human genetic disorders. To study if the induced chromosomal break points are specific for specific human genetic disorders. Human genetics disorders such as; retinitis pigmentosa, retinoblastoma, xeroderma pigmentosa and gonadal dysgenesis were used in our study. Suitable controls were maintained. The frequency and distribution pattern of chromosomal break points in individual chromosomes were determined in lymphocytes exposed to 50r of gamma radiation and 10?g/ml of bleomycin for 3h at G2. In normal individuals none of the unirradiated leukocyte cultures of any syndrome showed any accountable number of chromosomal aberrations. The frequency of radiation induced chromosomal break points showed a non random distribution pattern and frequently clustered at some specific chromosome regions to form hot spots. Lack of linear-quadratic dose response was observed in the lymphocyte exposed to bleomycin in normal individual. The frequency of chromosomal aberrations in the whole genome for the genetic disorders were higher than the controls and a varying distribution pattern of bleomycin induced breaks per cell was observed

2004-12-01

131

Development of 153Sm-bleomycin as a possible therapeutic complex  

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Due to interesting therapeutic properties of 153Sm and antineoplastic antibiotic, bleomycin(BLM), 153Sm-bleomycin (153Sm-BLM) was developed as a possible therapeutic compound using 153SmCl3 and BLM. The 153SmCl3 was obtained by thermal neutron flux (5 x 1013 n · cm-2 · s-1) of an enriched 152Sm2O3 sample,dissolved in acidic media.Under optimized conditions (room temperature, 45 min, 0.1 mg bleomycin for 740-3700 MBq 153SmCl3) a radiochemical purity over 98% was obtained shown by HPLC (Specific activity = 55 TBq/mM). The 153SmCl3 and 153Sm-BLM were administered into wild-type rats up to 96 h followed by biodistribution. The SPECT imaging of labeled compound in wild-type rats was performed and significant image pattern was observed for a radiolabeled bleomycin compound. The 153Sm-BLM is a potential therapeutic compound and our experiments on this compound have shown satisfactory quality, and stability suitable for future therapeutic studies. (authors)

2010-06-01

132

Bleomycin increases amikacin and streptomycin resistance in Escherichia coli harboring transposon Tn5.  

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The antitumor antibiotic bleomycin acts as a transcriptional inducer of the neo-ble-str operon of the transposon Tn5, increasing the resistance level to streptomycin and amikacin in Tn5-containing Escherichia coli. The mechanism may involve a recA-independent induction mediated by DNA damage.

1993-01-01

133

Bleomycin increases amikacin and streptomycin resistance in Escherichia coli harboring transposon Tn5.  

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The antitumor antibiotic bleomycin acts as a transcriptional inducer of the neo-ble-str operon of the transposon Tn5, increasing the resistance level to streptomycin and amikacin in Tn5-containing Escherichia coli. The mechanism may involve a recA-independent induction mediated by DNA damage. PMID:7694544

Blazquez, J; Martinez, J L; Baquero, F

1993-09-01

134

Preparation and Quality Control of Scandium-46 Bleomycin as a Possible Therapeutic Agent  

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Full Text Available Introduction: Due to interesting therapeutic properties of 46Sc and antineoblastic antibiotic, bleomycin (BLM, 46Sc-bleomycin (46Sc-BLM was developed as a possible therapeutic compound. Methods: In this work, Sc-46 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1 of natural metallic scandium sample followed by dissolution in acidic media as a substitute for 47Sc in radiolabeling studies which was further used for labeling of bleomycin (BLM followed by stability studies as well as biodistribution in wild-type rats. Results: Sc-46 was obtained in high radiochemical purity (ITLC, >99%, two systems as well as acceptable specific activity. At optimized conditions a radiochemical purity of 98% was obtained for 46Sc-BLM shown by ITLC (Specific activity, 740 GBq/mmole. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. Conclusion: Sc-BLM is a possible therapeutic agent in human malignancies and the efficacy of the compound should be tested in various tumor-bearing models.

Mohammad Ghannadi-Maragheh

2012-09-01

135

The Effects of Silymarin in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Background and Objectives: Silymarin, the active principle of Silybum marianum, has antifibrotic effects in hepatic fibrosis by several mechanisms. Since the pathogenesis of fibroproliferative diseases is similar, the effect of silymarin in bleomycin-induced pulmonary fibrosis was evaluated in this study.

Methods

Safaeian, L.

2012-01-01

136

Macrophage metalloelastase (MMP-12 deficiency does not alter bleomycin-induced pulmonary fibrosis in mice  

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Full Text Available Abstract Background Pulmonary fibrosis is characterized by excessive deposition of extracellular matrix in the interstitium resulting in respiratory failure. The role of remodeling mediators such as metalloproteinases (MMPs and their inhibitors (TIMPs in the fibrogenic process remains misunderstood. In particular, macrophage metalloelastase, also identified as MMP-12, is known to be involved in remodeling processes under pathological conditions. However, MMP-12 involvement in pulmonary fibrosis is unknown. Here we investigated fibrotic response to bleomycin in MMP-12 deficient mice. Materials and methods C57BL/6 mice, Balb/c mice and MMP-12 -/- mice with a C57BL/6 background received 0.3 mg bleomycin by intranasal administration. 14 days after, mice were anesthetized and underwent either bronchoalveolear lavage (BAL or lung removal. Collagen deposition in lung tissue was determined by Sircol™ collagen assay, MMP activity in BAL fluid was analyzed by zymography, and other mediators were quantified in BAL fluid by ELISA. Real time PCR was performed to assess gene expression in lung removed one or 14 days after bleomycin administration. Student t test or Mann & Whitney tests were used when appropriate for statistical analysis. Results The development of pulmonary fibrosis in "fibrosis prone" (C57BL/6 mice was associated with prominent MMP-12 expression in lung, whereas MMP-12 expression was weak in lung tissue of "fibrosis resistant" (Balb/c mice. MMP-12 mRNA was not detected in MMP-12 -/- mice, in conformity with their genotype. Bleomycin elicited macrophage accumulation in BAL of MMP-12 -/- and wild type (WT mice, and MMP-12 deficiency had no significant effect on BAL cells composition. Collagen content of lung was increased similarly in MMP-12 -/- and WT mice 14 days after bleomycin administration. Bleomycin elicit a raise of TGF-? protein, MMP-2 and TIMP-1 protein and mRNA in BAL fluids and lung respectively, and no significant difference was observed between MMP-12 -/- and WT mice considering those parameters. Conclusion The present study shows that MMP-12 deficiency has no significant effect on bleomycin-induced fibrosis.

Boichot Elisabeth

2006-02-01

137

A new measurement of the 7Li(d,p)8Li cross section and consequences for 7Be(p,?)8B  

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A novel scheme for measuring the cross section of the 7Be(p,?)8B reaction, the major source of high energy neutrinos from the sun, is presented. The scheme involves a strictly uniform particle beam and overcomes some of the recognized experimental uncertainties of previous measurements. A new measurement of ?[7Li(d,p)8Li] has been carried out using this setup, and the present value of ?[7Li(d,p)8Li]=155(8) mb at the top of the Ed(lab.)=776 keV resonance is compared with previous measurements. A new issue regarding both the (d,p) and (p,?) reactions has been examined: reaction-product nuclei which are backscattered out of the target. Measurements and simulations carried out in the course of this investigation are presented and discussed in the context of possible effects on the measured cross sections of these reactions. (orig.)

1998-02-23

138

A Systematic Review of Talc Compared with Bleomycin for Patients with Malignant Pleural Effusions  

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Full Text Available Background and objective Malignant pleural effusions are a common complication in advanced malignancy. Talc, bleomycin and the tetracyclines are the three most frequently used sclerosants. The aim of this study is to evaluate the efficacy and adverse effects of patients with malignant pleural effusions treated with talc and bleomycin. Methods We searched PubMed, Embase, the Cochrane Library, Chinese biomedicine literature database (CBM, CNKI, VIP, references of included studies for randomized controlled trials comparing talc with bleomycin for patients with malignant pleural effusions. The quality of included studies was assessed independently by two reviewers, discrepancies were resolved by discussion with the third person. We analyzed the data using Review Manager (version 5.0 software. Results Six studies totaling 224 patients were included. Meta analysis results were as follows: there was significantdifference in treatment success (RR=1.22, 95%CI: 1.05-1.42, recurrence rate (RR=0.31, 95%CI: 0.11-0.87 between talc group and bleomycin group, there was no significant difference between the two groups in case fatality rate (RR=1.39, 95%CI: 0.84-2.30, fever (RR=0.68, 95%CI: 0.24-1.94, pain (RR=0.22, 95%CI: 0.01-4.32. Conclusion Current evidence indicate that talc is super to bleomycin for patients with malignant pleural effusions in terms of improvingtreatment success and reducing recurrence rate, there is no significant difference between the two group with regard to casefatality rate, fever, pain, the results mentioned above still need to be confirmed by high quality, large sample, multicenter randomized controlled trial.

Yonggang WEI

2009-03-01

139

A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross  

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Richard Gelinas1,3, Elissa J Chesler2, Daphne Vasconcelos1, Darla R Miller2, Yue Yuan3, Kai Wang3, David Galas1,31Battelle Memorial Institute, Columbus, OH; 2Oak Ridge National Laboratory, Oak Ridge, TN; 3Institute for Systems Biology, Seattle, WA, USAAbstract: The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability ...

2011-01-01

140

Vascular damage in testicular cancer patients: a study on endothelial activation by bleomycin and cisplatin in vitro.  

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Following treatment with bleomycin- and cisplatin-containing chemotherapy, testicular cancer patients frequently develop vascular complications, which may result from damage to endothelial cells. Understanding bleomycin- and cisplatin-induced endothelial alterations may help to develop strategies to prevent or reduce vascular toxicity. The effects of bleomycin and cisplatin on proliferation and apoptosis of the human dermal microvascular endothelial cell line HMEC-1 were determined. In addition, modulation of drug-induced cytotoxicity by the free radical scavenger amifostine, the low molecular weight heparin dalteparin, the iron-chelator dexrazoxane, the HMG-CoA reductase inhibitor rosuvastatin and the PPAR agonist troglitazone was tested. Furthermore, the effects of bleomycin and cisplatin on endothelial activation measured by the expression of the intercellular adhesion molecule-1 (ICAM-1) and on two main proteins involved in fibrinolysis, tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1), were measured. Decreased endothelial cell survival induced by bleomycin and cisplatin coincided with the induction of apoptosis. Only troglitazone was able to protect the endothelial cells from both bleomycin- and cisplatin-induced cytotoxicity. At high concentrations, amifostine and dexrazoxane also protected HMEC-1 from drug-induced cytotoxicity. However, due to the required high (toxic) concentrations of both modulators no absolute cell survival benefit could be achieved. Both bleomycin and cisplatin induced up-regulation of ICAM-1, tPA and PAI-1. Summarizing, bleomycin and cisplatin induce alterations in the function of endothelial cells regarding proliferation, inflammation and fibrinolysis in vitro. Strategies aimed at these functions should be developed in order to ameliorate or prevent cytostatic agent-induced vascular damage. PMID:19956889

Nuver, Janine; De Haas, Esther C; Van Zweeden, Martine; Gietema, Jourik A; Meijer, Coby

2010-01-01

 
 
 
 
141

Proliferative kinetics and chromosome damage in trisomy 21 lymphocyte cultures exposed to gamma-rays and bleomycin  

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Lymphocytes from patients with Down's syndrome (trisomy 21) have been investigated for cell cycle kinetics, cell proliferation delays, and chromosomal aberrations after exposure to gamma-rays or bleomycin. Analysis by sister chromatid differential staining revealed that trisomy 21 lymphocytes started cell cycling about 5 hr earlier than did normal diploid lymphocytes after phytohemagglutinin stimulation as a whole, but that cycling trisomic and normal cells had the same mean cell cycle times. When exposed to gamma-rays or bleomycin in G0, trisomy 21 lymphocytes showed a 30% or, on average, 50% longer duration of cell turnover times, respectively, than normal cells; only bleomycin-treated trisomic cells had a biphasic dose-response. Frequencies of dicentrics and rings in first-division cells after gamma-ray or bleomycin exposure were twice as high in trisomic cells as in normal cells. The frequency of aberrations decreased by 50% (gamma-ray-exposed) or 65 to 85% (bleomycin-treated) through successive divisions; trisomic cells showed a more marked decline in aberration yields compared to normal cells after bleomycin treatment. These data support the idea that circulating lymphocytes in trisomy 21 patients have a shorter average life span or a younger average age

1984-01-01

142

CD19 Regulates Skin and Lung Fibrosis via Toll-Like Receptor Signaling in a Model of Bleomycin-Induced Scleroderma  

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Mice subcutaneously injected with bleomycin, in an experimental model of human systemic sclerosis, develop cutaneous and lung fibrosis with autoantibody production. CD19 is a general “rheostat” that defines signaling thresholds critical for humoral immune responses, autoimmunity, and cytokine production. To determine the role of CD19 in the bleomycin-induced systemic sclerosis model, we investigated the development of fibrosis and autoimmunity in CD19-deficient mice. Bleomycin-treated wil...

Yoshizaki, Ayumi; Iwata, Yohei; Komura, Kazuhiro; Ogawa, Fumihide; Hara, Toshihide; Muroi, Eiji; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Tedder, Thomas F.; Sato, Shinichi

2008-01-01

143

Folk medicine Terminalia catappa and its major tannin component, punicalagin, are effective against bleomycin-induced genotoxicity in Chinese hamster ovary cells.  

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Terminalia catappa L. is a popular folk medicine for preventing hepatoma and treating hepatitis in Taiwan. In this paper, we examined the protective effects of T. catappa leaf water extract (TCE) and its major tannin component, punicalagin, on bleomycin-induced genotoxicity in cultured Chinese hamster ovary cells. Pre-treatment with TCE or punicalagin prevented bleomycin-induced hgprt gene mutations and DNA strand breaks. TCE and punicalagin suppressed the generation of bleomycin-induced intracellular free radicals, identified as superoxides and hydrogen peroxides. The effectiveness of TCE and punicalagin against bleomycin-induced genotoxicity could be, at least in part, due to their antioxidative potentials. PMID:10773401

Chen, P S; Li, J H; Liu, T Y; Lin, T C

2000-05-01

144

Molecular dynamics simulations exploring the interaction between DNA and metalated bleomycin  

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Full Text Available Bleomycin (Blm is a natural antibiotic with antitumour activity, used as a combination drug in treatment of various types of cancers. Blm intercalates with DNA and will in the presence of a redox metal ion and molecular oxygen form an activated bleomycin complex capable of releasing free radicals and subsequently leading to DNA cleavage. The present theoretical work was carried out to better understand the interaction between DNA and Blm using different metal co-factors (Co and Fe. Binding energies and structural properties were analysed for both the complexes. The results show that Blm binds stronger to DNA when complexed with Fe, and provides a better structural orientation compared to the CoBlm complex in order to abstract the H4' hydrogen of deoxyribose that initiates the DNA strand cleavage process. The short distance between the iron-bound peroxide and the deoxyribose H4' furthermore supports the previously proposed direct abstraction mechanism.

Leif A. Eriksson

2011-05-01

145

Structural studies on metallobleomycins: The interaction of Pt(II and Pd(II with bleomycin  

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Full Text Available Two of the most successful chemotherapeutic agents used in the treatment of several neoplasias are bleomycin and cisplatin. Both drugs attack the DNA leading to the cancer cells death via different mechanisms. In view of the fact that the combination with each other leads to enhanced activity with less sever side effects, we have undertaken NMR studies on the complexes formed between bleomycin and PtII, PdII, cisplatin and transplatin. Herein we present a brief review of the studies on metallobleomycins which were carried out by our lab and others, as an outline of the results obtained using NMR in combination to circular dichroism spectroscopy. Our data indicate that in most cases and under several conditions studied, both metal ions form similar complexes with BLM, while more than one species are present in the solution. Structural implications and comparisons with other metallobleomycins are being discussed.

NIKOS KATSAROS

2003-05-01

146

Preparation and quality control of radiolabelled cobalt-57 bleomycins for oncological studies  

International Nuclear Information System (INIS)

[55Co] bleomycin has been widely used in ontological studies. Due to relative short half life of cobalt-55, optimization and feasibility studies for determination of the best labeling conditions is preferably performed using cobalt-57. In this study, the optimization of complexation conditions for time, temperature and ligand concentration were performed. The best labeling yield was obtained at room temperature in pH of 4-7, using 0.4 mCi of 57CoCl2 with 0.3mg of BLM in 30 minutes. The final radiopharmaceutical solution underwent common quality control tests, validating our future studies for animal scanning studies using [55Co]bleomycin complex

2007-01-01

147

Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin  

International Nuclear Information System (INIS)

A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis

1983-01-01

148

Discovery in PET/CT of an acute pulmonary toxicity with rapidly fatal bleomycin  

International Nuclear Information System (INIS)

Purpose: we report the case of a patient treated by chemotherapy for a Hodgkin disease showing after treatment an important pulmonary uptake that appears bilateral and symmetric on PET in connection with an acute toxicity at the preclinical stage. Conclusions: an intense and diffuse pulmonary uptake of the 18F.D.G. during the chemotherapy, including particularly the bleomycin, can reveal an acute serious pulmonary toxicity and potentially deadly at the pre-symptomatic stage. (N.C.)

2010-05-08

149

Microsomal Prostaglandin E Synthase-1 Deficiency Exacerbates Pulmonary Fibrosis Induced by Bleomycin in Mice  

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Full Text Available Microsomal prostaglandin E2 synthase-1 (mPGES-1, an inducible enzyme that converts prostaglandin H2 (PGH2 to prostaglandin E2 (PGE2, plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1?/? mice exhibited more severe fibrotic lesions with a decrease in PGE2 content in lungs after bleomycin treatment when compared with wild type (mPGES-1+/+ mice. The mPGES-1 expression levels and PGE2 content were also decreased in bleomycin-treated mPGES-1+/+ mice compared to saline-treated mPGES-1+/+ mice. Moreover, in both mPGES-1?/? and mPGES-1+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2 and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5, siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-?1 (TGF-?1-induced ?-smooth muscle actin (?-SMA protein expression, and the increase was reversed by treatment of PGE2, selective EP2 agonist and focal adhesion kinase (FAK inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE2-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients.

Bo Wei

2014-04-01

150

SRT1720, a SIRT1 Activator, Aggravates Bleomycin-Induced Lung Injury in Mice  

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Diagnosis and management of interstitial lung diseases (ILDs), caused by lung epithelial injury followed by apoptosis, are often challenging. It has been controversial whether the SIRT1 protein, a principal modulator of longevity due to caloric restriction, ameliorates or aggravates ILD in animal models. Here we examined the effect of SRT1720, a syn- thetic activator of SIRT1, on bleomycin-induced lung injury in a mouse model and apoptosis in cultured epithelial cells. Oral intubation of SRT1...

Shingo Imanishi; Ryuji Hayashi; Tomomi Ichikawa; Kensuke Suzuki; Masakiyo Sasahara; Takashi Kondo; Hirofumi Ogawa; Kazuyuki Tobe

2012-01-01

151

Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin  

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Abstract Background Cluster of differentiation 69 (CD69), an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM)-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT) and CD69-deficient (CD69

Yamauchi Keita; Kasuya Yoshitoshi; Kuroda Fuminobu; Tanaka Kensuke; Tsuyusaki Junichi; Ishizaki Shunsuke; Matsunaga Hirofumi; Iwamura Chiaki; Nakayama Toshinori; Tatsumi Koichiro

2011-01-01

152

Combination therapy for advanced oral squamous cell carcinoma with radiation and bleomycin, 1  

International Nuclear Information System (INIS)

Twenty-five patients of advanced oral cancers (squamous cell carcinoma) were treated with combination of radiation and bleomycin in the first course of treatment, and then treated with either Ra needle or 198Au grain implantation, 2 to 3 weeks after the first course of treatment for severe mucositis. The treatments were performed during 1975 to 1977. In the combination therapy, external irradiation (daily 250 rad) of Telecobalt ?-ray or Betatron electron beam was given by 4 fractionations per week during 2.5 to 3 weeks (2,500 to 3,000 rad). Bleomycin (5 mg) was injected intramuscularly about 30 min before the irradiation, giving a total of 50 to 60 mg during therapy. In the second course of therapy, Ra needle or 198Au grain implants were employed in 14 cases and further external irradiation was given for the remaining cases except one which had two primary origins of cancer in the tongue and liver. As a result of the combination therapy, 12 primary tumors out of 25 cases markedly regressed (more than 50% regression) and by subsequent radiotherapy, 11 primary tumors out of 24 were completely controlled during more than 14 months of follow-up observation. The tongue cancer in one exceptional case was controlled by the combination of radiation (3,000 rad) and bleomycin (60 mg) alone. Fifteen of 25 patients are still alive, while 10 patients died of cancer. This therapy of combined irradiation and bleomycin seems to be effective on advanced oral cancers because the local tumor control rate increased markedly. (author)

1980-01-01

153

Low dose irradiation, tegafur and bleomycin in oil for rectal cancer  

International Nuclear Information System (INIS)

A histopathological survey of surgical materials from 143 patients with rectal carcinoma subjected to chemotherapy or to low-dose radiotherapy combined with tegafur and bleomycin in oil was carried out. The radiotherapy brought about better results than chemotherapy alone. In 4 out of the 58 patients treated with the radiochemotherapy, no cancer cells could be found. Exfoliation of cohorts of cancer cells may occur into the rectal lumina in selected cases of rectal carcinoma thus treated, resulting in cancer cell elimination. (author)

1984-01-01

154

The counter regulatory response induced by CpG oligonucleotides prevents bleomycin induced pneumopathy  

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Abstract Bleomycin (BLM) induces life-threatening pneumonitis and pulmonary fibrosis in 20% of patients, limiting its use as a chemotherapeutic agent. Oligonucleotides expressing immunostimulatory CpG motifs (CpG ODN) stimulate cells that express Toll-like receptor 9 to initiate an inflammatory response. This short-lived inflammation is physiologically suppressed by a counter-regulatory process that peaks five days later. Using a murine model of BLM-induced lung injury, the effect o...

Kinjo Takeshi; Tomaru Koji; Haines Diana C; Klinman Dennis M

2012-01-01

155

Bleomicina: un modelo de fibrosis pulmonar / Bleomycin: a lung fibrosis animal model  

Scientific Electronic Library Online (English)

Full Text Available SciELO Mexico | Language: Spanish Abstract in spanish La bleomicina es un glicopéptido utilizado para el tratamiento del cáncer cuyo potencial terapéutico está limitado por su toxicidad pulmonar. El efecto citotóxico depende de la dosis e involucra el desarrollo de neumonitis que progresa a fibrosis; las células epiteliales alveolares son el blanco pri [...] ncipal del daño inducido por la bleomicina. Se considera que la muerte de células epiteliales alveolares por apoptosis es un evento clave en el inicio y la progresión de la fibrosis pulmonar (FP) que se caracteriza por el depósito excesivo de moléculas de la matriz extracelular, principalmente de colágenas fibrilares en el parénquima pulmonar. En la investigación básica de la FP, la bleomicina se ha utilizado como el principal agente fibrogénico en modelos animales. Durante los últimos años, el modelo de bleomicina desarrollado en ratones trasgénicos se ha empleado para elucidar in vivo el papel de un gran número de biomoléculas involucradas en la FP. Abstract in english Bleomycin is a glycopeptide used for cancer treatment, but the therapeutic potencial of this drug is limited by its lung toxicity. The cytotoxic effect of bleomycin is dose-dependent and involves pneumonitis that proceeds to lung fibrosis (LF). Alveolar epithelial cells are the main target of bleomy [...] cin induced injury. Alveolar epithelial cell death by apoptosis is considered as a key event in the initiation and progression of LF, that is characterized by excessive deposition of extracellular matrix, mainly fibrilar collagens in the lung parenchyma. Bleomycin has been used as the main fibrogenic agent in animal models in LF basic research; in recent years, a bleomycin model developed in transgenic mice has been used to elucidate the in vivo role of a great number of biomolecules involved in LF.

Sandra, Cabrera Benítez.

156

TGF? signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment  

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The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-? (TGF?) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGF? receptor 2 (TGF?R2) in lung epithelium were generated and crossed to cell fate reporter mice...

Degryse, Amber L.; Tanjore, Harikrishna; Xu, Xiaochuan C.; Polosukhin, Vasiliy V.; Jones, Brittany R.; Boomershine, Chad S.; Ortiz, Camila; Sherrill, Taylor P.; Mcmahon, Frank B.; Gleaves, Linda A.; Blackwell, Timothy S.; Lawson, William E.

2011-01-01

157

Protective Role of Andrographolide in Bleomycin-Induced Pulmonary Fibrosis in Mice  

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Idiopathic pulmonary fibrosis (IPF) is a chronic devastating disease with poor prognosis. Multiple pathological processes, including inflammation, epithelial mesenchymal transition (EMT), apoptosis, and oxidative stress, are involved in the pathogenesis of IPF. Recent findings suggested that nuclear factor-?B (NF-?B) is constitutively activated in IPF and acts as a central regulator in the pathogenesis of IPF. The aim of our study was to reveal the value of andrographolide on bleomycin-indu...

2013-01-01

158

Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice  

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Abstract Background Pulmonary fibrosis (PF) is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE) 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF. Methods PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by us...

2010-01-01

159

Microsomal prostaglandin E synthase-1 deficiency exacerbates pulmonary fibrosis induced by bleomycin in mice.  

Science.gov (United States)

Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), plays an important role in a variety of diseases. So far, the role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1-/-) mice exhibited more severe fibrotic lesions with a decrease in PGE2 content in lungs after bleomycin treatment when compared with wild type (mPGES-1+/+) mice. The mPGES-1 expression levels and PGE2 content were also decreased in bleomycin-treated mPGES-1+/+ mice compared to saline-treated mPGES-1+/+ mice. Moreover, in both mPGES-1-/- and mPGES-1+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2) and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5), siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-?1 (TGF-?1)-induced ?-smooth muscle actin (?-SMA) protein expression, and the increase was reversed by treatment of PGE2, selective EP2 agonist and focal adhesion kinase (FAK) inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE2-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients. PMID:24756129

Wei, Bo; Cai, Linhong; Sun, Dan; Wang, Yanhua; Wang, Cairui; Chai, Xiaoyu; Xie, Feng; Su, Ming; Ding, Fangrui; Liu, Jie; Yang, Jichun; Guan, Youfei; Liu, Xinmin

2014-01-01

160

Novel DNA photocleaving agents with high DNA sequence specificity related to the antibiotic bleomycin A2.  

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We have designed and synthesized a series of novel DNA photocleaving agents which break DNA with high sequence specificity. These compounds contain the non-diffusible photoactive p-nitrobenzoyl group covalently linked via a dimethylene (or tetramethylene) spacer to thiazole analogues of the DNA binding portion of the antibiotic bleomycin A2. By using a variety of 5' or 3' 32P-end labeled restriction fragments from plasmid pBR322 as substrate, we have shown that photoactive bithiazole compound...

Kuroda, R.; Satoh, H.; Shinomiya, M.; Watanabe, T.; Otsuka, M.

1995-01-01

 
 
 
 
161

Bleomycin delivery by osmotic minipump: similarity to human scleroderma interstitial lung disease.  

Science.gov (United States)

The interstitial lung diseases (ILD) include a large number of chronic, progressive, irreversible respiratory disorders involving pulmonary fibrosis, the most common of which are idiopathic pulmonary fibrosis and scleroderma lung disease (SSc ILD). Because bleomycin causes lung fibrosis when used in cancer chemotherapy, it is used to model human ILD in rodents. In most studies, bleomycin has been delivered directly into the lung by intratracheal or intraoral administration. Here we have compared the effects in mice of bleomycin delivered directly into the lungs (direct model) or systemically using osmotic minipumps (pump model) to determine which more closely resembles human ILD. The pump model is more similar to human SSc ILD in that: 1) lung injury/fibrosis is limited to the subpleural portion of the lung in the pump model and in SSc ILD, whereas the entire lung is affected in the direct model; 2) conversely, there is massive inflammation throughout the lung in the direct model, whereas inflammation is limited in the pump model and in SSc ILD; 3) hypertrophic type II alveolar epithelial cells are present at high levels in SSc ILD and in the pump model but not in the direct model; and 4) lung fibrosis is accompanied by dermal fibrosis. The pump model is also move convenient and humane than the direct model because there is less weight loss and mortality. PMID:24583879

Lee, Rebecca; Reese, Charles; Bonner, Michael; Tourkina, Elena; Hajdu, Zoltan; Riemer, Ellen C; Silver, Richard M; Visconti, Richard P; Hoffman, Stanley

2014-04-15

162

Pharmacokinetics of 57Co-bleomycin A5 in animals with different inoculated tumors  

International Nuclear Information System (INIS)

The examination of rats with different inoculated tumors rhabdomyosarcoma M-1 (RMS), sarcoma 45 (S-45), Pliss lymphosarcoma (PLS) and Walker carcinoma (WK) revealed, that the pharmacokinetics of 57Co-bleomycin in tumor-bearing animals did not essentially depend on the histological type of the tumor. The specific activity quotients in the tumors as well as in the muscle tissue did not show differences and had their maxima 3 h after application of the preparation (RMS = 11.7 +- 2.70; S-45 = 10.9 +- 2.05; PLS = 9.52 +- 1.14; WK = 9.16 +- 1.93). The storage maximum of 57Co-bleomycin A5 per g tumor tissue was for RMS and PLS after 5 min. (0.83 +- 0.10 and 0.71 +- 0.06 %, resp., of the applied activity), for S-45 and WK after one hour (0.87 +- 0.14 and 0.86 +- 0.15 %, resp.). The results of the kinetic distribution of the labelled bleomycin A5 showed that the moments of visualization of the tumors varied in the different inoculated tumors in intervals from 3 to 48 h after application. (author)

1983-01-01

163

Esophageal cancer treated by low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta  

International Nuclear Information System (INIS)

Eight patients with esophageal cancer were treated by a new treatment schedule consisting of low dose irradiation, crescendo cisplatin and bleomycin polyacrylate pasta. As monitored endoscopically, their therapeutic responses were satisfactory, and seven out of the eight survived for a range of 3 to 18 months and still active at work or ''cancer-free''. The seventh of the eight suffers from a second malignancy of adenocarcinoma of the cardia, different from the initial squamous cell carcinoma at the lower esophagus which had successfully been treated 3 months before. The present therapeutic design aims at treatment of lymphatic spreads in the adjacent structures as well as the original tumor in the esophagus and submucosal invasions. It is basically a consecutive, multimodal integration of selective concentration of therapeutic effects (extensive radiotherapy, topical application of bleomycin polyacrylate pasta, lymphatic chasing with colloidal bleomycin, and spatial concentration of cisplatin as the result of radiation-induced inflammations), perpetuation of the repairable DNA damage, and biological amplifications (protection against esophageal perforation with polyacrylate coating, and specific cancer cell recruitment). Application of the present therapeutic design is being expanded to treatment of cancer at other specific sites such as the head and neck tumors and rectal cancer with undeniable prospects. (author)

1982-01-01

164

Time course of matrix metalloproteases and tissue inhibitors in bleomycin-induced pulmonary fibrosis  

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Full Text Available To investigate simultaneously localization and relative activity of MMPs during extracellular matrix (ECM remodeling in bleomycin-induced pulmonary fibrosis in rat, we analyzed the time course of the expression, activity and/or concentration of gelatinases MMP-2 and MMP-9, collagenase MMP-1, matrylisin MMP-7, TIMP-1 and TIMP-2, both in alveolar space (cellular and extracellular compartments and in lung tissue. MMP and TIMP expression was detected (immunohistochemistry in lung tissue. MMP activity (zymography and TIMP concentration (ELISA were evaluated in lung tissue homogenate (LTH, BAL supernatant (BALs and BAL cell pellet (BALp 3, 7, 14, and 28 days after bleomycin intratracheal instillation. Immunohistochemistry showed an extensive MMP and TIMP expression from day 7 in a wide range of structural and inflammatory cells in treated rats. MMP-2 was present mainly in epithelia, MMP-9 in inflammatory cells. MMP-2 and MMP-9 activity was increased respectively in BAL fluid and BAL cells, with a peak at day 7. TIMP-1 and TIMP-2 concentration (ELISA enhancement was delayed at day 14. In conclusion gelatinases and their inhibitors are significantly activated during bleomycin-induced pulmonary fibrosis. Marked changes in gelatinases activity are observed early in the alveolar compartment, with a prevailing extracellular activity of MMP-2 and a predominant intracellular distribution of MMP-9, while enzyme activity changes in lung parenchyma were less evident. In the repairing phase the reduction of gelatinases activity is synchronous with a peak of alveolar concentration of their inhibitors.

C Fenoglio

2006-12-01

165

miR-29 inhibits bleomycin-induced pulmonary fibrosis in mice.  

Science.gov (United States)

Loss of microRNA-29 (miR-29) is known to be a mechanism of transforming growth factor-? (TGF-?)-mediated pulmonary fibrosis, but the therapeutic implication of miR-29 for pulmonary fibrosis remains unexplored. The present study investigated whether miR-29 had therapeutic potential for lung disease induced by bleomycin in mice. In addition, the signaling mechanisms that regulated miR-29 expression were investigated in vivo and in vitro. We found that miR-29 was a downstream target gene of Smad3 and negatively regulated by TGF-?/Smad signaling in fibrosis. This was evidenced by the findings that mice or pulmonary fibroblasts null for Smad3 were protected against bleomycin or TGF-?1-induced loss of miR-29 along with fibrosis in vivo and in vitro. Interestingly, overexpression of miR-29 could in turn negatively regulated TGF-? and connective tissue growth factor (CTGF) expression and Smad3 signaling. Therefore, Sleeping Beauty (SB)-mediated miR-29 gene transfer into normal and diseased lung tissues was capable of preventing and treating pulmonary fibrosis including inflammatory macrophage infiltration induced by bleomycin in mice. In conclusion, miR-29 is negatively regulated by TGF-?/Smad3 and has a therapeutic potential for pulmonary fibrosis. SB-mediated miR-29 gene therapy is a non-invasive therapeutic strategy for lung disease associated with fibrosis. PMID:22395530

Xiao, Jun; Meng, Xiao-Ming; Huang, Xiao R; Chung, Arthur Ck; Feng, Yu-Lin; Hui, David Sc; Yu, Cheuk-Man; Sung, Joseph Jy; Lan, Hui Y

2012-06-01

166

Mobile Internet Protocol Analysis.  

Science.gov (United States)

Mobile Internet Protocol (IP) is a proposed standard that builds on the current Internet Protocol by making the fact that a user is mobile transparent to applications and higher level protocols such as Transmission Control Protocol (TCP) and User Datagram...

L. J. Brachfeld

1999-01-01

167

Histology protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Tim D. Hewitson & Ian A. Darby (Eds Humana press, Totowa, New Jersey (USA Series: Springer Protocols Methods in Molecular Biology, Volume 611, 2010 Pages: 230; € 83.15 ISBN: 978-1-60327-344-2 Impressive as it can sounds in the era that Biology see a clear dominance of reductionism with the idea that complexity can be disentagled more and more thanks to the use of molecular tools, the reader will remain fascinated by this slim and agile volume devoted to bring together what apparently are two separeted words: molecular biology and histology. Simply remembering to the youngest scientists.....

CarloAlberto Redi

2010-06-01

168

Structure of the excited states of "1"1Be reached through the reaction d("1"0Be,p)"1"1Be  

International Nuclear Information System (INIS)

The one-neutron transfer reaction d("1"0Be,p)"1"1Be has been studied at 32 A.MeV at GANIL with a "1"0Be secondary beam. Protons were detected by the silicon strip array MUST. The ground state and excited states of "1"1Be at 0.32, 1.78 and 3.41 MeV were populated, demonstrating the feasibility of transfer reactions induced by radioactive beams leading to bound and unbound states. A DWBA (distorted wave born approximation) analysis indicates for the 3.41 MeV state spin and parity 3/2"+ or 5/2"+ and a spectroscopic factor of 0.18 or 0.11, respectively. A broad structure centered at 10 MeV is also observed and corresponds to transfer to the 1d sub-shells. If one assumes that only the 1d3/2 orbital contributes to this structure, the splitting of the 1d neutron states in "1"1Be is estimated to be 6.3 MeV. Using a 2-particle-RPA (random phase approximation) model, we have shown that neutron-neutron correlations play an important role in the inversion between the 2s1/2 and 1p1/2 neutron states in "1"1Be. (author)

2003-01-01

169

Comparing the Effect of Physical Modalities on Permeabilisation of Cells to Bleomycin in Balb/C Mice  

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Full Text Available Background: Some physical factors may facilitate the entry of chemotherapeutic drugs to the cells. In this study, permeability level of tumor cells of murine breast adenocarcinoma to Bleomycin was compared with 5 minutes ultrasonic exposure vs. magnetic field of 3.5 Tesla in Balb/c mice.Materials and Methods: In this experimental-applied study, 80 five-week female Balb/c mice were purchased from Pasteur Institute of Tehran. After 10 days, skin tumors of mice were induced through Homograft, and they were randomly classified after tumor reached a treatable size. In ultrasound combination group, intratumoral injection of bleomycin was performed on anesthetized mice and three minutes later, the mice, which were placed in the sonication chamber, were put in a water tank in the exposure position, and the tumor was exposed to ultrasound for 5 minutes. In the magnetic field group, mice were placed in a handmade chamber after intratumoral injection of bleomycin. Three minutes after injection of bleomycin, eight pulses of 3.5 Tesla magnetic fields with 1Hz frequency were applied to each one of the tumors.Results: It yield that, eight 3.5 Tesla pulses of magnetic field, was slightly more effective than 5 min ultrasonic irradiation in cells permeability to bleomycin, but these two physical factors had no statistically significant difference.Conclusion: Tests showed that these two physical factors have similar effects and use of each depends on the position of the patient and the medical center's facilities.

Bahram Yousefian

2012-07-01

170

Preparation of [66Ga]bleomycin complex as a possible PET radiopharmaceutical  

International Nuclear Information System (INIS)

Several radiolabeled bleomycin derivatives have been developed for imaging and/or therapy of neoplastic tissues. The most important imaging compounds contain indium-111, cobalt- 57, and rhodium-105. In our previous studies we have prepared radiolabeled bleomycin complexes such as gallium-67 as therapeutic and/or imaging agents. Our recent studies on the preparation and tumour imaging properties of [67Ga]bleomycin in normal and tumour-bearing mice showed a good tumour/blood and tumour/muscle ratio suggesting that it is an appropriate diagnostic agent. Due to the interesting properties and increasing importance of positron emission tomography, we investigated the possibility of incorporating 66Ga as a positron emitter with an antineoplastic compound, bleomycin, for use in tumour imaging. We optimized 66Ga complex formation conditions with bleomycin, to develop [66Ga]BLM. We hereby report the production of 66Ga, preparation, optimization, stability, and formulation studies of [66Ga]-bleomycin complex. Targetry: An electroplated 66Zn target on a copper backing plate was irradiated at an angle of 6 degrees toward the proton beam in order to achieve higher production yield. The target was cooled by a flow of 18 deg. C distilled water with a rate of 50 Lit/min. Chemical Separation: The irradiated target was dissolved by 10 N HCl (15 ml, H2O2 added) and the solution was passed through a cation exchange resin (Dowex 50 Wx8, H+ form) (h:10 cm, diameter:1 cm). The resulting high-purity [66Ga]GaCl3 solution was used directly in the labeling step. Labeling of bleomycin with [66Ga]GaCl3: [66Ga]GaCl3 (0.25-2.5 mCi) dissolved in acidic medium obtained above (0.5-2 ml) was transferred to a 2 ml-vial and pH was adjusted to various pHs (1-7) using 1M HCl and/or 1M NaOH. The mixture was evaporated by slight warming under a nitrogen flow. A mixture of BLM (0.25-2.5 mg) in normal saline (0.1 ml) was then added and was heated at different temperatures (25, 50, 80, and 100 deg. C) and was cooled in an ice bath, and rapidly sent for use. The active solution was checked for radiochemical purity by polymer-backed silica gel layer chromatography using a 1:1 mixture of 10% ammonium acetate and methanol as mobile phase. The final solution was then passed through a 0.22 ?m filter and pH was adjusted to 5-7 by the addition of 1 M sodium acetate buffer. Radionuclide purity: The gamma spectroscopy of the final sample was carried out by HPGe detector, and showed a radionuclidic purity higher than 99 % showing the presence of 511, 834, and 1039 keV gamma energies, all of which are resulted from 66Ga. [66Ga]BLM complex in final product: Stability studies were based on the previous studies performed for other radiolabeled bleomycins (5). A sample of [66Ga]BLM (0.5 mCi) was kept at room temperature for 5 hrs while checked by RTLC every half an hour. A micropipet sample (50 ?l) was taken from the shaking mixture and the ratio of free radiogallium to [66Ga]BLM was checked by radio thin layer chromatography (eluent: 10% NH4OAc buffer and methanol (1:1). Total labeling and formulation of [66Ga]BLM took about 60 min, with a yield of 97%. A suitable specific activity product was formed via insertion of [66Ga]gallium cation. No unlabelled and/or labeled by-products were observed upon RTLC analysis of the final preparations. The radio-labeled complex was stable in aqueous solutions for at least 24 h and no significant amount of other radioactive species were detected by HPLC 24 h after labeling. Trace amounts of [66Ga]gallium chloride (?2%) were detected by TLC. RTLC showed that radiochemical purity of the [66Ga]labeled components was higher than 98%. In contrast to other labeled bleomycins, [66Ga]bleomycin, is a PET radiotracer with a rather long half life, and the high chemical stability of this radiopharmaceutical makes it a very suitable diagnostic agent

2005-11-14

171

A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross.  

Science.gov (United States)

The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs) were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain. PMID:23226052

Gelinas, Richard; Chesler, Elissa J; Vasconcelos, Daphne; Miller, Darla R; Yuan, Yue; Wang, Kai; Galas, David

2011-01-01

172

The effect of AT1 receptor blockade on bax and bcl-2 expression in bleomycin-induced pulmonary fibrosis  

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Full Text Available ABSTRACT Background and the purpose of the study: Recent studies have indicated the role of apoptosis and angiotensin in the pathogenesis of bleomycin induced-pulmonary fibrosis. Losartan, an angiotensin type 1 receptor (AT1R antagonist, has ameliorated apoptosis and fibrosis from bleomycin. In this study, alterations in the expression of apoptosis-regulatory genes (bcl-2 and bax were investigated in different cells of lung tissue of mice treated with bleomycin in the presence of losartan. Methods: Losartan (10 mg/kg, i.p. was given to mice two days before administration of bleomycin (3 U/kg and throughout the test period. After two weeks, lung tissues of mice were evaluated for fibrosis by biochemical measurement of collagen deposition and semiquantitative analysis of pathological changes of the lung. The expression of bcl-2 and bax was assessed by immunohistochemical assay using biotin-streptavidin staining method on paraffin-embedded lung tissues. Results and major conclusion: Pre-treatment with losartan significantly (P < 0.05 reduced the increase in lung collagen content and also inhibited the histological changes induced by bleomycin. Immunohistochemical studies showed that losartan significantly (P < 0.05 reduced the bax/bcl-2 expression ratio in the alveolar epithelial cells, lymphocytes, macrophages and interstitial myofibroblasts. Losartan also inhibited the bcl-2 upregulation which was educed by bleomycin in neutrophils. By reduction of bax/bcl-2 ratio as a determinant of susceptibility of a cell to apoptosis, losartan exerted protective effects on the alveolar epithelial cells that may be important in the amelioration of pulmonary fibrosis. These results may help to better understanding of the role of angiotensin II and apoptosis in pulmonary fibrosis.

L Safaeian

2009-03-01

173

Tissue uptakes of 67 Ga-bleomycin and carrier free 67 Ga in fibrosarcoma-bearing mic  

International Nuclear Information System (INIS)

67Gallium-bleomycin complex was prepared using Thakour method. Radio-thin-layer-chromatography of prepared complex showed A2 and B2 radio peaks with Rf at 0.7 and 0.4 respectively with a purity of above % 95. Tissue uptake of 67 Gallium-bleomycin complex and 67GaCl3 in twelve tissues including tumor, blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content, bladder and the total body were counted by well counter at 1,2,4,24 and 48 hours post injection of radiopharmaceuticals. Uptakes of tissues are expressed as percent injected dose per gram of tissue. The clearance rate of 67 Gallium-bleomycin complex was 1.75 - 1.95 times faster than 67GaCl3 at all time intervals. Bladder uptakes of 67 Gallium-bleomycin complex were highest among twelve tissues at 1,2 and 4 hours after injection, then falling rapidly after 24 and 48 hours. Blood uptake of 67 Gallium-bleomycin complex was lower than 67GaCl3 in all time intervals. Colon content uptake of 67 Gallium-bleomycin complex was highest among twelve tissues at 2 and 4 hours post injection. Tumor to tissue activity ratios were also calculated, showing an increase of tumor to blood and muscle ratios. Tumor to blood ratio increased from 0.3 at 1 hour to 5.3 at 48 hours. Activity ratios of muscle increased from 0.5 at 1 hour to 5.5 at 48 hours. Whole body counting of animals showed that effective half lives of 67 Gallium-bleomycin complex and 67GaCl3 were about 1 and 15 hours respectively, which renders faster excretion of 67 Gallium-bleomycin complex. Biodistribution data clearly indicates that prepared complex in comparison with carrier free 67Ga (67GaCl3) has two main advantages: 1) high tumor to soft tissue uptake ratio that make it suitable for tumor imaging. 2) faster excretion specially at first three hours post injection.In addition complex is stable in vitro and in vivo

2004-01-01

174

Sensitivity to genotoxic effects of bleomycin of blood lymphocytes of people residing in villages of ChNPP exclusion zone  

International Nuclear Information System (INIS)

On purpose of comparative determination of cell repair system activity of people residing without permission in the villages of ChNPP exclusion zone and of Yahotyn district, Kiev region (control group) the chromosome sensitivity of peripheral blood lymphocytes to genotoxic effect of bleomycin in vitro was studied. Chromatid break frequency per cell was a criterium for the estimation. It was found a significantly higher sensitivity to bleomycin in ChNPP exclusion zone self-settlers' group due to cell reaction of people younger than 60. For the elderly people there was revealed no significant difference

2002-01-01

175

Monitoring of /sup 57/Co-bleomycin delivery to brain metastases and their tumors of origin  

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The concentration of cobalt-57 (/sup 57/Co)-labeled bleomycin delivered to three brain metastases and to their tumors of origin in the lungs was measured using a single-photon emission computerized tomography technique. In two brain metastases the /sup 57/Co-bleomycin concentration measured at different times after the intravenous injection was significantly lower than that in the originating lung tumors (p less than 0.01 and p less than 0.001). In these two patients, the tumor cumulative concentration (TCC) of drug in the brain neoplasm compared to the lung carcinoma was 12.92 versus 15.12 and 10.30 versus 19.74 micrograms/cc/min. In the third patient there was no significant difference in drug concentration between the tumor in the brain and in the lung (TCC 16.02 vs. 15.09 micrograms/cc/min). There was a significant difference in the drug TCC between the three brain metastases: the difference between the lowest and highest concentrations was more than 50% (10.3 vs. 16.02 micrograms/cc/min). When the concentration in the tumor over time (CT(t)) of the /sup 57/Co-bleomycin was compared in the brain and lung tumors, a good correlation was found in each of the three cases (r = 0.93, 0.99, and 0.97). This suggests that the difference in drug uptake between brain metastases and their originating lung tumor is a quantitative rather than a qualitative phenomenon. The results show that the amount of drug to which brain metastases are exposed varies and may be very low in some tumors; therefore, effectiveness of drug delivery may play a role in the nonresponsiveness of brain metastases to treatment.

Front, D.; Even-Sapir, E.; Iosilevsky, G.; Israel, O.; Frenkel, A.; Kolodny, G.M.; Feinsud, M.

1987-10-01

176

Protective effect of royal jelly on fertility and biochemical parameters in bleomycin-?induced male rats  

Science.gov (United States)

Background: Bleomycin (BL) is a glycopeptide antibiotic obtained from the bacterium Streptomyces verticillus which is routinely used for treatment of human cancers. Royal jelly (RJ) is a production from the hypo pharyngeal, mandibular and post cerebral glands of nurse bees. RJ consists of 66% water, 15% sugars, 5% lipids, and 13% proteins, essential amino acids and vitamins. Objective: The aim of present study was to evaluate protective effect of royal jelly on sperm parameters and malondialdehyde (MDA) production in rat. Materials and Methods: Forty adult male wistar rats (220±20gr) were randomly divided into 4 groups (n=10). Control group (CG) received normal saline 10 ml/kg twice a week with Intraperitoneal (I.P) for 48 days (0.3 ml/rat(. Royal Jelly group (RJG) received jelly (100 mg/kg daily) for 48 days orally. Bleomycin group (BLG) received BL (10 mg/kg twice a week) with I.P for 48 days. Royal Jelly+ Bleomycin group (RJ+BLG) received royal Jelly (100 mg/kg /day) orally concomitant with BL administration. Sperm count, motility, and viability were investigated and chromatin quality and DNA integrity were also analyzed. Serum testosterone and MDA concentrations were measured as well. Results: BL caused decline significantly (ptestosterone concentration compared to control group while significant (ptestosterone and MDA concentrations. Conclusion: The present results support the idea that BL adversely affects sperm parameters and MDA and the RJ with antioxidant properties has positive effects on these parameters. This article extracted from M.Sc. thesis. (Tayebeh amirshahi)

Amirshahi, Tayebeh; Najafi, Gholamreza; Nejati, Vahid

2014-01-01

177

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2, when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS...

1997-01-01

178

Modulation of the clastogenic activity of ionizing radiation and bleomycin by the aminothiol WR-1065  

International Nuclear Information System (INIS)

WR-1065 (2-[(aminopropyl)amino]ethanethiol) reduces the induction by ionizing radiation of genetic damage, including DNA single- and double-strand breaks, chromosomal aberrations, micronuclei, and hprt mutations in mammalian cells. The effectiveness of WR-1065 as a radioprotector is apparently enhanced by its tendency, a a cationic thiol, to concentrate near DNA. The authors have studied the modulation by WR-1065 of the induction of chromosome aberrations and micronuclei in G0 human lymphocytes by ionizing radiation and by the radiomimetic chemical bleomycin

1993-01-01

179

Tumor localization with gallium, radiolabeled bleomycin, thallium, selenium, carbon and nitrogen radionuclides. Oncology overview  

International Nuclear Information System (INIS)

Oncology Overviews are a service of the International Cancer Research Data Bank (ICRDB) Program of the National Cancer Institute, intended to facilitate and promote the exchange of information between cancer scientists by keeping them aware of literature related to their research being published by other laboratories throughout the world. Each Oncology Overview represents a survey of the literature associated with a selected area of cancer research. It contains abstracts of articles which have been selected and organized by researchers associated with the field. Contents: Gallium scans; Radiolabeled bleomycin scans; Thallium scans; Selenium scans; Carbon radionuclide scans; Nitrogen radionuclide scans; Multiagent studies

1981-01-01

180

Relative tissue concentrations and radiation dosimetry of 111In-bleomycin  

International Nuclear Information System (INIS)

The study was undertaken to determine relative tissue concentrations on postsurgical specimens and to collect sufficient patient data to make meaningful estimates of the absorbed radiation dose for patients undergoing diagnostic studies with 111In-bleomycin. The mean tumor-to-muscle ratios ranged from 6.78 to 16.05 for a variety of tumors. These values were slightly greater than those of tumor-to-blood. The ratios of tumor-to-fat and tumor-to-skin were lower since those tissues seemed to concentrate more activity

1974-02-12

 
 
 
 
181

Platinum complexes inhibit repair of potentially lethal damage following bleomycin treatment.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The SCC-25 cell line is a well-established line derived from a human squamous carcinoma of the head and neck. The capacity of this cell line for recovery from potentially lethal damage following X-ray treatment has been documented. The survival curve of stationary phase SCC-25 cells exposed to various concentrations of bleomycin is biphasic with an initial sensitive phase and a less sensitive second phase as is common for many cell lines. Stationary phase SCC-25 cells were exposed to 100 mU m...

1987-01-01

182

Platinum complexes inhibit repair of potentially lethal damage following bleomycin treatment.  

Science.gov (United States)

The SCC-25 cell line is a well-established line derived from a human squamous carcinoma of the head and neck. The capacity of this cell line for recovery from potentially lethal damage following X-ray treatment has been documented. The survival curve of stationary phase SCC-25 cells exposed to various concentrations of bleomycin is biphasic with an initial sensitive phase and a less sensitive second phase as is common for many cell lines. Stationary phase SCC-25 cells were exposed to 100 mU ml-1 of bleomycin for 1 h. The drug was removed and the cells were allowed various periods to recover from potentially lethal damage. After 24 h, the SCC-25 cells showed a recovery ratio (R/R0) of 7.0 which corresponded to an immediate survival at a drug level of 27 mU ml-1, a dose 3.7-fold less than the exposure concentration of 100 mU ml-1. Over the course of the first 4 h following bleomycin exposure, 0.5 microM CDDP was a very effective inhibitor of potentially lethal damage repair, giving a R/R0 of 1.1 or nearly complete inhibition of recovery. Between 2 and 4 h the R/R0 was 1.6-1.8 with CDDP and 4.1-5.3 without CDDP indicating appreciable inhibition of recovery. Plant (10 microM) and Plato (10 microM) produced potentially lethal damage recovery inhibition patterns very similar to that of CDDP. After 1 h the recovery ratios in the presence of Plant and Plato were 1.1-1.3. Between 2 and 4 h, Plato and Plant gave recovery ratios of 1.8-2.3 and 1.6-1.9, respectively. NIPt and Pt(terpy) were examined at both 10 microM and 25 microM for their ability to inhibit potentially lethal damage recovery after bleomycin treatment. After 1 h, NIPt gave a recovery ratio of 1.3-1.4, and after 2-4 h the recovery ratio was 1.7-2.6. Pt(terpy) gave recovery ratios of 1.3-1.6 after 1 h and 1.5-1.8 after 24 h. PMID:2436643

Holden, S A; Teicher, B A; Boeheim, K; Weichselbaum, R R; Ervin, T J

1987-03-01

183

Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.  

LENUS (Irish Health Repository)

The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

Quintyne, Keith Ian

2011-09-01

184

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: English Abstract in portuguese Antioxidantes de ocorrência natural têm sido exaustivamente estudados quanto a sua capacidade de proteger organimos e células contra danos oxidativos. Muitos constituintes das plantas, incluindo cúrcuma e curcumina, parecem ser potentes antimutágenos e antioxidantes. Os efeitos de cúrcuma e curcumin [...] a na freqüência de aberrações cromossômicas induzidas pelo agente radiomimético bleomicina (BLM) foram investigados em células do ovário de hamster chinês (CHO). Três concentrações de cada droga, cúrcuma (100, 250 e 500 mg/ml) e curcumina (2,5, 5,0 e 10 mg/ml), foram combinadas com BLM (10 mg/ml) em células CHO tratadas durante as fases G1/S, S ou G2/S do ciclo celular. Nem cúrcuma nem curcumina evitaram o dano cromossômico induzido pela BLM em fase alguma do ciclo celular. Ao contrário, a potenciação da clastogenicidade da BLM pelo curcumina foi nitidamente observada em células tratadas durante as fases S e G2/S. A curcumina também se mostrou clastogênica na dose de 10 mg/ml nos protocolos de tratamento de 9 e 13 h. Contudo, o mecanismo exato pelo qual a curcumina produziu efeitos potenciadores e clastogênicos permanece desconhecido. Abstract in english Naturally occurring antioxidants have been extensively studied for their capacity to protect organisms and cells from oxidative damage. Many plant constituents including turmeric and curcumin appear to be potent antimutagens and antioxidants. The effects of turmeric and curcumin on chromosomal aberr [...] ation frequencies induced by the radiomimetic agent bleomycin (BLM) were investigated in Chinese hamster ovary (CHO) cells. Three concentrations of each drug, turmeric (100, 250 and 500 mg/ml) and curcumin (2.5, 5 and 10 mg/ml), were combined with BLM (10 mg/ml) in CHO cells treated during the G1/S, S or G2/S phases of the cell cycle. Neither turmeric nor curcumin prevented BLM-induced chromosomal damage in any phases of the cell cycle. Conversely, a potentiation of the clastogenicity of BLM by curcumin was clearly observed in cells treated during the S and G2/S phases. Curcumin was also clastogenic by itself at 10 µg/ml in two protocols used. However, the exact mechanism by which curcumin produced clastogenic and potentiating effects remains unknown.

Araújo, Maria Cristina P.; Dias, Francisca da Luz; Kronka, Sergio N.; Takahashi, Catarina S..

185

The Effect of Bleomycin to the Mitotic Index who were Exposed to Radiation Chronically  

Directory of Open Access Journals (Sweden)

Full Text Available Beginning with the therapeutic dose and increasing three differentdoses and three different periods of time Bleomycin (Bleomycin 0.3 ?g/ml, 3?g/ml and 30 ?g/ml, 6, 24, 48 hours were added to blood which was beingcultured on 5 samples who were exposed to radiation chronically.The mitotic index in the lymphocyte culture was determined by means ofcounting 1000 cells from preparations belong to control and experimentgroups.The mitotic index was showed difference value to the differencebleomycin dose and the between difference samples. As the mitotic indexvalue (Per 1000 cell 10.86 for the control group, this value fall to 8.73 at0.3 ?g/ml, 5.0 at 3 ?g/ml and 3.93 at 30 ?g/ml. There were no significantdifferences between control group and 0.3 ?g/ml, 3 ?g/ml and 30 ?g/ml(P>0.05. An important fall was seen between control group and 3 ?g/mland 30 ?g/ml, 0.3 ?g/ml group and 3 ?g/ml, 30 ?g/ml (P<0.01.

Hilmi ?si

2004-01-01

186

Serum bleomycin-detectable iron in patients with thalassemia major with normal range of serum iron.  

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Full Text Available "Free" iron, a potentially radical-generating low mass iron, and not found in normal human blood, was increased in the serum of blood-transfused thalassemia major patients seen in the Yangon General Hospital, Yangon, Myanmar (Burma. The low mass iron was detected by the bleomycin assay. Fifty-one blood samples were analyzed (from 28 males and 23 females. High "free" iron was detected in 47 sera samples from thalassemia patients. Serum ferritin, which reflects the body store iron, was higher than the normal range (10-200 ng/ml in 49 patients. On the other hand, serum iron of 39 sera samples fell within the normal range (50-150 micrograms/dl. Four were less than 50 micrograms/dl and eight were more than 150 micrograms/dl. Almost all the patients' sera of normal or higher serum iron level contained "free" iron. Thus, almost all the sera from thalassemic patients from Myanmar contain bleomycin-detectable iron, even when serum iron is within the normal range. In developing countries where undernutrition is prevalent (serum albumin in these patients was 3.6 +/- 0.4 g/dl, P < 0.0001 vs. control value of 4.0 - 4.8 g/dl, normal serum iron does not preclude the presence of free iron in the serum.

Han,Khin Ei

1995-06-01

187

Povidone-iodine and bleomycin in the management of malignant pleural effusion.  

Science.gov (United States)

Malignant pleural effusion is a common complication in certain malignancies. Pleurodesis is the best option most of the time. The purpose of this study was to compare the choice of belomycin with povidone-iodine, which is not only determined by the efficacy of the agent but also by its cost, accessibility, safety, ease of administration and the number of administrations to achieve a complete response. We performed a randomized clinical trial on 39 patients presenting with symptomatic malignant pleural effusion. Patients were selected and randomly assigned to undergo chemical pleurodesis with either bleomycin or povidone-iodine. Primary characteristics of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. A complete response was obtained in 79% of belomycin group and 75% of povidone-iodine group which was not statistically significant. Patients on belomycin treatment had a significantly lower score for dyspnea in one month follow up. This was significant after controlling for age, pain score and dyspnea score after drainage, using general linear model. Due to similar effect and significant cost advantage between bleomycin and povidone-iodine, we conclude that povidone- iodine is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions. PMID:22052141

Alavi, Ali Asghar; Eshraghi, Mohsen; Rahim, Mohammad Bagher; Meysami, Ali Pasha; Morteza, Afsaneh; Hajian, Hanieh

2011-01-01

188

Povidone-Iodine and Bleomycin in the Management of Malignant Pleural Effusion  

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Full Text Available "nMalignant pleural effusion is a common complication in certain malignancies. Pleurodesis is the best option most of the time. The purpose of this study was to compare the choice of belomycin with povidone-iodine, which is not only determined by the efficacy of the agent but also by its cost, accessibility, safety, ease of administration and the number of administrations to achieve a complete response. We performed a randomized clinical trial on 39 patients presenting with symptomatic malignant pleural effusion. Patients were selected and randomly assigned to undergo chemical pleurodesis with either bleomycin or povidone-iodine. Primary characteristics of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. A complete response was obtained in 79% of belomycin group and 75% of povidone-iodine group which was not statistically significant. Patients on belomycin treatment had a significantly lower score for dyspnea in one month follow up. This was significant after controlling for age, pain score and dyspnea score after drainage, using general linear model. Due to similar effect and significant cost advantage between bleomycin and povidone-iodine, we conclude that povidone- iodine is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions.

Ali Asghar Alavi

2011-09-01

189

Effect of 0.25 ppm Ozone exposure on pulmonary damage induced by bleomycin  

Directory of Open Access Journals (Sweden)

Full Text Available To study the effect of ozone in a chronically damaged lung, we used a bleomycin (BLM induced pulmonary fibrosis model. Both endotracheal instillation of BLM and O3 exposure both produce lung inflammation and fibrosis. Oxidative stress would be a common mechanism of damage for both BLM and O3. Our aim was to assess lung injury induced by 5 and 60 days of intermittent exposure to 0.25 ppm O3 in rats with bleomycin-induced pulmonary fibrosis. Thirty-day-old Sprague Dawley rats were endotracheally instilled with BLM (1 U/100 g body weight and, 30 days later, exposed to 0.25 ppm O3 (0.25 ppm 4 h per day, 5 days a week. Histopatology controls were instilled with saline and breathing room air. Histopathological evaluation of lungs was done 5 and 60 days after O3 exposure. BLM-induced lung damage did not change after 60 days of intermittent O3 exposure. Five days of O3 exposure increased the mean score of BLM-induced pulmonary inflammation and fibrosis (p=0.06. Frequency of bronchopneumonia increased from 1/7 to 6/6 (p <0.001, suggesting that a short-term exposure to O3 in a previously damaged lung might be a risk factor for developing further lung injury

MANUEL OYARZÚN

2005-01-01

190

Hairpin DNA sequences bound strongly by bleomycin exhibit enhanced double-strand cleavage.  

Science.gov (United States)

Clinically used bleomycin A5 has been employed in a study of double-strand cleavage of a library of 10 hairpin DNAs originally selected on the basis of their strong binding to bleomycin. Each of the DNAs underwent double-strand cleavage at more than one site, and all of the cleavage sites were within, or in close proximity to, an eight-base-pair region of the duplex that had been randomized to create the original library. A total of 31 double-strand cleavage sites were identified on the 10 DNAs, and 14 of these sites were found to represent coupled cleavage sites, that is, events in which one of the two strands was always cleaved first, followed by the associated site on the opposite strand. Most of these coupled sites underwent cleavage by a mechanism described previously by the Povirk laboratory and afforded cleavage patterns entirely analogous to those reported. However, at least one coupled cleavage event was noted that did not conform to the pattern of those described previously. More surprisingly, 17 double-strand cleavages were found not to result from coupled double-strand cleavage, and we posit that these cleavages resulted from a new mechanism not previously described. Enhanced double-strand cleavages at these sites appear to be a consequence of the dynamic nature of the interaction of Fe·BLM A5 with the strongly bound hairpin DNAs. PMID:24548300

Roy, Basab; Hecht, Sidney M

2014-03-19

191

Response of radiation-sensitive mutants of Saccharomyces cerevisiae to lethal effects of bleomycin  

International Nuclear Information System (INIS)

Haploid and diploid strains of yeast containing genes conferring radiation-sensitivity were studied under growing and nongrowing experimental conditions for their relative sensitivities to growth-inhibitory effects of bleomycin (BM). The rad1, rad2, rad3, rad4, rad5 (and allelic rev2), rad7, rad10, rad11, rad12, rad14, rad15, rad16 and rev3 strains exhibited responses similar to normal (Rad+) yeast strains. It is concluded from these findings that the excision repair function deficient in several of these mutant strains is not important for repair of bleomycin-induced damages in yeast. The sensitive strains contained rad6, rad9, rad18, rad22, rad50, rad51, rad52, rad53, rad54, rad55, rad56, rad57 and rs1. Strains bearing rad8 or rad19 could not be classified unambiguously. With one exception, all rad mutants found very sensitive to BM were sensitive to X-rays, suggesting that some aspect of the repair of BM- and X-ray induced damages in yeast may be similar. Sensitivities to BM and radiation co-segregated in pedigrees following meiosis, and several BM-resistant revertants isolated from two rad6 mutant strains sensitive to BM, X-rays and UV were cross-resistant to all three agents. These results confirm that the rad mutants were responsible for the cross-sensitivities in the original strains. (Auth.)

1978-01-01

192

Hairpin DNA Sequences Bound Strongly by Bleomycin Exhibit Enhanced Double-Strand Cleavage  

Science.gov (United States)

Clinically used bleomycin A5 has been employed in a study of double-strand cleavage of a library of 10 hairpin DNAs originally selected on the basis of their strong binding to bleomycin. Each of the DNAs underwent double-strand cleavage at more than one site, and all of the cleavage sites were within, or in close proximity to, an eight-base-pair region of the duplex that had been randomized to create the original library. A total of 31 double-strand cleavage sites were identified on the 10 DNAs, and 14 of these sites were found to represent coupled cleavage sites, that is, events in which one of the two strands was always cleaved first, followed by the associated site on the opposite strand. Most of these coupled sites underwent cleavage by a mechanism described previously by the Povirk laboratory and afforded cleavage patterns entirely analogous to those reported. However, at least one coupled cleavage event was noted that did not conform to the pattern of those described previously. More surprisingly, 17 double-strand cleavages were found not to result from coupled double-strand cleavage, and we posit that these cleavages resulted from a new mechanism not previously described. Enhanced double-strand cleavages at these sites appear to be a consequence of the dynamic nature of the interaction of Fe·BLM A5 with the strongly bound hairpin DNAs.

2014-01-01

193

The LIM-Only Protein FHL2 Attenuates Lung Inflammation during Bleomycin-Induced Fibrosis  

Science.gov (United States)

Fibrogenesis is usually initiated when regenerative processes have failed and/or chronic inflammation occurs. It is characterised by the activation of tissue fibroblasts and dysregulated synthesis of extracellular matrix proteins. FHL2 (four-and-a-half LIM domain protein 2) is a scaffolding protein that interacts with numerous cellular proteins, regulating signalling cascades and gene transcription. It is involved in tissue remodelling and tumour progression. Recent data suggest that FHL2 might support fibrogenesis by maintaining the transcriptional expression of alpha smooth muscle actin and the excessive synthesis and assembly of matrix proteins in activated fibroblasts. Here, we present evidence that FHL2 does not promote bleomycin-induced lung fibrosis, but rather suppresses this process by attenuating lung inflammation. Loss of FHL2 results in increased expression of the pro-inflammatory matrix protein tenascin C and downregulation of the macrophage activating C-type lectin receptor DC-SIGN. Consequently, FHL2 knockout mice developed a severe and long-lasting lung pathology following bleomycin administration due to enhanced expression of tenascin C and impaired activation of inflammation-resolving macrophages.

Schied, Tanja; Chiquet-Ehrismann, Ruth; Loser, Karin; Vogl, Thomas; Ludwig, Stephan; Wixler, Viktor

2013-01-01

194

Carbon monoxide-bound hemoglobin-vesicles for the treatment of bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

Carbon monoxide (CO) has potent anti-inflammatory and anti-oxidant effects. We report herein on the preparation of a nanotechnology-based CO donor, CO-bound hemoglobin-vesicles (CO-HbV). We hypothesized that CO-HbV could have a therapeutic effect on idiopathic pulmonary fibrosis (IPF), an incurable lung fibrosis, that is thought to involve inflammation and the production of reactive oxygen species (ROS). Pulmonary fibril formation and respiratory function were quantitatively evaluated by measuring hydroxyproline levels and forced vital capacity, respectively, using a bleomycin-induced pulmonary fibrosis mice model. CO-HbV suppressed the progression of pulmonary fibril formation and improved respiratory function compared to saline and HbV. The suppressive effect of CO-HbV on pulmonary fibrosis can be attributed to a decrease in ROS generation by inflammatory cells, NADPH oxidase 4 and the production of inflammatory cells, cytokines and transforming growth factor-? in the lung. This is the first demonstration of the inhibitory effect of CO-HbV on the progression of pulmonary fibrosis via the anti-oxidative and anti-inflammatory effects of CO in the bleomycin-induced pulmonary fibrosis mice model. CO-HbV has the potential for use in the treatment of, not only IPF, but also a variety of other ROS and inflammation-related disorders. PMID:24811261

Nagao, Saori; Taguchi, Kazuaki; Sakai, Hiromi; Tanaka, Ryota; Horinouchi, Hirohisa; Watanabe, Hiroshi; Kobayashi, Koichi; Otagiri, Masaki; Maruyama, Toru

2014-08-01

195

Percutaneous sclerotherapy of massive macrocystic lymphatic malformations of the face and neck using fibrin glue with OK-432 and bleomycin.  

Science.gov (United States)

Picibanil (OK-432) and bleomycin have been used as alternative sclerosing agents for lymphatic malformations. This study evaluated the clinical curative effect of sclerotherapy using fibrin glue combined with OK-432 and bleomycin for the treatment of macrocystic lymphatic malformations of the face and neck. Fifteen paediatric patients (6 males; 9 females, aged 13 months to 14 years) who had received percutaneous sclerotherapy for massive macrocystic lymphatic malformations of the face and neck were retrospectively reviewed. Affected regions included the neck, parotid region and parapharynx, mouth floor, face and cheek, and orbital regions. All patients showed preoperative symptoms of space-occupying lesions between 4 cm × 5 cm and 12 cm × 16 cm in size. Fibrin glue with OK-432 and bleomycin was injected under general anaesthesia. All patients received preoperative and follow-up CT scans. Outcomes were assessed by three surgeons. All patients exhibited mid-facial swelling for 3-4 weeks after surgery, but no major complications. Follow-up periods ranged from 8 to 16 months. Eight lesions were completely involuted, five were mostly involuted, and two were partially involuted. Percutaneous sclerotherapy using fibrin glue with OK-432 and bleomycin provided a simple, safe, and reliable alternative treatment for massive macrocystic lymphatic malformations of the face and neck. PMID:21367582

Chen, W-l; Huang, Z-q; Chai, Q; Zhang, D-m; Wang, Y-y; Wang, H-j; Wang, L; Fan, S

2011-06-01

196

Radio-isotope scanning using labelled bleomycin in positive and differential diagnosis of primary and secondary malignant pulmonary lesions  

International Nuclear Information System (INIS)

A lung scan using bleomycin labelled with cobalt 57 was carried out in 308 patients representing 191 primary malignant tumours, 48 pulmonary metastases and 69 benign lesions. The primary and secondary malignant lesions always gave rise to a hyperactive focus except in 8 cases of primary lung tumour. The negative examination may be explained, either by the small size of the lesion or by radiotherapy in progress. Among the benign lesions, only advanced tuberculosis and very inflammatory lung diseases frequently took up labelled bleomycin (15 hyperactive foci out of 69 benign lesions). Quantitative measurements, i.e. ratio of the lesional activity/activity of healthy lung tissue, were carried out in all patients. The malignant lesions were usually more active than the benign lesions. There was no definite correlation between the uptake of labelled bleomycin and the histological nature of the lesion. However, undifferentiated and anaplastic carcinomas were often more active. One should emphasize that these results show that a hyperactive focus has a 94% chance of being a carcinoma. The absence of bleomycin uptake means that there is a 92% chance of a benign lesion

1975-01-01

197

Association of the emerging carbapenemase NDM-1 with a bleomycin resistance protein in Enterobacteriaceae and Acinetobacter baumannii.  

Science.gov (United States)

The carbapenemase NDM-1 has been identified recently in Enterobacteriaceae and Acinetobacter baumannii as a source of multidrug resistance, including resistance to carbapenems. By analyzing the immediate genetic environment of the bla(NDM-1) carbapenemase gene among a series of NDM-1-producing enterobacterial isolates, a novel gene (ble(MBL), for ble gene associated with the metallo-?-lactamase NDM-1) was identified. The ble(MBL) gene encodes a novel bleomycin resistance protein (BRP), named BRP(MBL), that shares weak similarities with known BRPs (less than 60% amino acid identity). The expression of BRP(MBL) conferred resistance to bleomycin and to bleomycin-like molecules in Enterobacteriaceae and A. baumannii. The bla(NDM-1) and ble(MBL) genes were coexpressed under the control of the same promoter, located upstream of the bla(NDM-1) gene and at the extremity of the insertion sequence ISAba125. Most of the NDM producers possessed the ble(MBL) gene. Although BRP(MBL) did not modify the growth or death rates of Escherichia coli under experimental conditions, it suppressed the mutation rate of hypermutable E. coli and therefore may stabilize the plasmid-borne bla(NDM-1) gene. This study suggests that the emerging carbapenemase NDM-1 is selected by bleomycin-like molecules, and that BRP(MBL) producers (and consequently NDM producers) are better suited to various environments. PMID:22290943

Dortet, Laurent; Nordmann, Patrice; Poirel, Laurent

2012-04-01

198

Further characterizations of bleomycin-sensitive (blm) mutants of Saccharomyces cerevisiae with implications for a radiomimetic model.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Direct selection for 12 mutations (blm) conferring hypersensitivities to lethal effects of bleomycins in Saccharomyces cerevisiae resulted in mutants exhibiting cross-hypersensitivity to ionizing radiation and hydrogen peroxide. Remaining mutations did not confer cross-hypersensitivity to radiation. All blm mutations were recessive, except codominant blm3-1, and were assigned to seven complementation groups.

Moore, C. W.

1991-01-01

199

The Role of Strain Variation in BAX and BCL-2 Expression in Murine Bleomycin-Induced Pulmonary Fibrosis  

Directory of Open Access Journals (Sweden)

Full Text Available This study hypothesized that the expression of apoptosis-regulatory genes, such as BCL-2 and BAX may be affected by genetic variation in bleomycin-induced pulmonary fibrosis in C57BL/6 and NMRI mice. Pulmonary fibrosis induced by single intratracheal dose of bleomycin (3 U kg-1. After 2 weeks, lung samples were analyzed for collagen deposition, pathological changes and expression of BCL-2 and BAX. The fibrotic lung changes were similar in both strains. The immunohistochemical assay using a biotin-streptavidin technique showed no significant difference in immunoreactivity for BCL-2 protein between the controls and bleomycin-treated C57BL/6 mice. However, in NMRI mice, the expression of BCL-2 was significantly (p<0.05 upregulated in myofibroblasts and neutrophils. The expression of BAX protein was significantly (p<0.05 upregulated in alveolar epithelial cells of both strains and downregulated in myofibroblasts and lymphocytes of the lung tissues of C57BL/6 mice and also in lymphocytes of NMRI mice at 2 weeks after bleomycin instillation. These results confirm the role of BCL-2 and BAX proteins in the pathogenesis of pulmonary fibrosis and suggest that the expression of apoptotic regulatory genes may be specific in different cell types in various strains.

L. Safaeian

2008-01-01

200

A genetic approach to the prediction of drug side effects: bleomycin induces concordant phenotypes in mice of the collaborative cross  

Directory of Open Access Journals (Sweden)

Full Text Available Richard Gelinas1,3, Elissa J Chesler2, Daphne Vasconcelos1, Darla R Miller2, Yue Yuan3, Kai Wang3, David Galas1,31Battelle Memorial Institute, Columbus, OH; 2Oak Ridge National Laboratory, Oak Ridge, TN; 3Institute for Systems Biology, Seattle, WA, USAAbstract: The antineoplastic drug bleomycin leads to the side effect of pulmonary fibrosis in both humans and mice. We challenged genetically diverse inbred lines of mice from the Collaborative Cross with bleomycin to determine the heritability of this phenotype. Sibling pairs of mice from 40 lines were treated with bleomycin. Lung disease was assessed by scoring lung pathology and by measuring soluble collagen levels in lavage fluid. Serum micro ribonucleic acids (miRNAs were also measured. Inbred sibling pairs of animals demonstrated high coinheritance of the phenotypes of disease susceptibility or disease resistance. The plasma levels of one miRNA were clearly correlated in sibling mice. The results showed that, as in humans, the lines that comprise the Collaborative Cross exhibited wide genetic variation in response to this drug. This finding suggests that the genetically diverse Collaborative Cross animals may reveal drug effects that might be missed if a study were based on a conventional mouse strain.Keywords: collaborative cross, drug side effects, genetic diversity, disease susceptibility, disease resistance, bleomycin, lung disease

Gelinas R

2011-07-01

 
 
 
 
201

Targeting the hedgehog-glioma-associated oncogene homolog pathway inhibits bleomycin-induced lung fibrosis in mice.  

Science.gov (United States)

Idiopathic pulmonary fibrosis has been associated with the reactivation of developmental pathways, notably the Hedgehog-Glioma-associated oncogene homolog (GLI) pathway. In this study, we determined whether the Hedgehog pathway was activated in bleomycin-induced lung injury in mice, and whether targeting the Hedgehog-Gli pathway could decrease bleomycin-induced lung fibrosis. After intratracheal injection of bleomycin on Day 0, C57Bl6 mice received GDC-0449 (an inhibitor of Smoothened, the transducer of the pathway), or 2,2'-[[Dihydro-2-(4-pyridinyl)-1,3(2H,4H)-pyrimidinediyl]bis(methylene)]bis[N,N dimethylbenzenamine (GANT61; an inhibitor of GLI transcription factors in the nucleus), from Day 7 to Day 13. At Day 14, whole-lung homogenates were obtained for morphological analysis, assessment of cell apoptosis and proliferation, collagen quantification, and evaluation of profibrotic (transforming growth factor-?, connective tissue growth factor, plasminogen activator inhibitor 1, vascular endothelial growth factor-A) and proinflammatory mediators (IL-1?) expression. We showed that the Hedgehog pathway was activated in bleomycin-induced lung fibrosis on Day 14 after injury, with an increased lung expression of the ligand, Sonic Hedgehog, and with increased messenger RNA expression and nuclear localization of GLI1 and GLI2. Inhibition of Smoothened with GDC-0449 did not influence the development of bleomycin-induced lung fibrosis. By contrast, the inhibition of GLI activity with GANT61 decreased lung fibrosis and lung collagen accumulation, and promoted an antifibrotic and anti-inflammatory environment. Our results identify the hedgehog-Gli pathway as a profibrotic pathway in experimental fibrosis. Inhibition of the Hedgehog-Gli pathway at the level of GLI transcriptional activity could be a therapeutic option in fibrotic lung diseases. PMID:24450438

Moshai, Elika Farrokhi; Wémeau-Stervinou, Lidwine; Cigna, Natacha; Brayer, Stephanie; Sommé, Joëlle Marchal; Crestani, Bruno; Mailleux, Arnaud A

2014-07-01

202

Early diagnosis of malignant diseases with 111-In-bleomycin and evaluation of their response to radiotherapy and chemotherapy  

International Nuclear Information System (INIS)

A comparative evaluation of "1"1"1In-Bleomycin and "6"7Ga-Citrate, in 92 patients with malignant pulmonary conditions and in 15 with benign, was carried out. In addition sup(99m)Tc-Citrate was also evaluated in 47 patients with malignant and in 10 with benign diseases. Our results indicate superior performance of "6"7Ga-Citrate with 79% true positive examinations for malignant lesions as compared with 65% for "1"1"1In-Bleomycin and 45,6% for sup(99m)Tc-Citrate. It should be stressed that in no case a data processing device was used with any of these agents. In no case sup(99m)Tc-Citrate gave positive results in benign pulmonary diseases. On the contrary "1"1"1In-Bleomycin gave false positive results in 5% of benign disorders as compared with 20% of "6"7Ga-Citrate. We conclude that in the case of benign pulmonary disease the possibility to obtain false positive results is 0% with sup(99m)Tc-Citrate, 5% with "1"1"1In-Bleomycin and 20% with "6"7Ga-Citrate. In the case of malignant pulmonary lesions, on the other hand, the possibility of true positive examinations is 79% for gallium citrate, 65% for "1"1"1In-Bleomycin and 45% for sup(99m)Tc-Citrate. In addition the examination with the "6"7Ga-Citrate gives higher percentages of 3+ score in malignant conditions

1978-01-01

203

In vivo measurements of the fraction of dose of bleomycin labeled with cobalt 57 delivered to human tumors  

International Nuclear Information System (INIS)

Concentrations of bleomycin labeled with cobalt 57 (Co-bleo) over time were measured in vivo in 17 patients with 32 sites of lymphoma and 18 patients with lung tumors after administration of the same dose of bleomycin. There were marked variations in individual tumor drug concentrations even among tumors with the same histologic type, indicating that the tumor concentration of this drug in individuals cannot be predicted from the administered dose. Also, tumor concentration could not be predicted from the area under the concentration over time curve (AUC) of Co-bleo in the blood; there was no correlation (r = 0.53) between the AUC and the concentration in the tumor at any point in time between 30 minutes and 8 hours after injection. There was no significant difference in the percent of the injected dose per milliliter (%ID/ml) which was delivered to the tumor when low and high amounts of bleomycin were administered to the same patient. Also, a good correlation (r = 0.88) between the %ID/ml over time was found when injection of low and high doses of bleomycin were compared. The results indicate that using quantitative single photon emission computed tomography (SPECT) and a labeled tracer dose it is possible to predict what fraction of the dose of a chemotherapeutic drug will concentrate in an individual patient's tumor in vivo. They also show that, for bleomycin, escalation of dose will result in a proportional increase of tumor concentration. This increase depends on individual properties of tumors which can be measured quantitatively in vivo by SPECT and are expressed as percent of %ID/ml of tumor tissue

1991-05-15

204

Transport Protocol Throughput Fairness  

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Interest continues to grow in alternative transport protocols to the Transmission Control Protocol (TCP). These alternatives include protocols designed to give greater efficiency in high-speed, high-delay environments (so-called high-speed TCP variants), and protocols that provide congestion contro...

Saleem Bhatti; Martin Bateman

2009-01-01

205

Protocol Implementation Generator  

DEFF Research Database (Denmark)

Users expect communication systems to guarantee, amongst others, privacy and integrity of their data. These can be ensured by using well-established protocols; the best protocol, however, is useless if not all parties involved in a communication have a correct implementation of the protocol and all necessary tools. In this paper, we present the Protocol Implementation Generator (PiG), a framework that can be used to add protocol generation to protocol negotiation, or to easily share and implement new protocols throughout a network. PiG enables the sharing, verification, and translation of communication protocols. With it, partners can suggest a new protocol by sending its specification. After formally verifying the specification, each partner generates an implementation, which can then be used for establishing communication. We also present a practical realisation of the Protocol Implementation Generator framework based on the LySatool and a translator from the LySa language into C or Java.

Carvalho Quaresma, Jose Nuno; Probst, Christian W.

2010-01-01

206

Some transplantable substance in spent medium obtained from the plateau culture of HeLa cells affecting the sensitivity to bleomycin  

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The cytotoxic effect of bleomycin (BLM) on HeLa cells grown at plateau phase was investigated and compared with that at exponential phase. Cells were cultured in F10 medium supplemented 10% calf serum and antibiotics before exposure to BLM. Results show that the sensitivity seen at low dose and short time exposures was extended in the spent medium. It is suggested that there is some unknown substance in the spent medium that enhances cell killing by bleomycin.

Miyamoto, T.; Terasima, T.

1986-05-01

207

Treatment Outcomes of AIDS-Associated Kaposi's Sarcoma under a Routine Antiretroviral Therapy Program in Lilongwe, Malawi: Bleomycin/Vincristine Compared to Vincristine Monotherapy  

Science.gov (United States)

Purpose Despite Kaposi's sarcoma (KS) being the most prevalent AIDS-associated cancer in resource limited settings, optimal treatment options remain unknown. We assessed whether bleomycin/vincristine compared to vincristine monotherapy was associated with improved treatment outcomes for AIDS-associated KS among patients initiating combination antiretroviral therapy (cART) in Malawi. Methods All patients initiating cART and chemotherapy for AIDS-related KS were identified from an electronic data system from the HIV Lighthouse Clinic from 2002 to 2011. Treatment responses were compared between patients receiving vincristine monotherapy and vincristine/bleomycin. Binomial regression models were implemented to assess probability of tumor improvement for patients receiving vincristine/bleomycin compared to vincristine monotherapy after a complete cycle of chemotherapy (9–10 months). A chi-squared test was used to compare changes in CD4 count after six months of chemotherapy. Results Of 449 patients with AIDS-associated KS on chemotherapy, 94% received vincristine monotherapy and 6% received bleomycin/vincristine. Distribution of treatment outcomes was different: 29% of patients on vincristine experienced tumor improvement compared to 53% of patients on bleomycin/vincristine. Patients receiving bleomycin/vincristine were 2.25 (95% CI: 1.47, 3.44) times as likely to experience tumor improvement as to those on vincristine monotherapy. This value changed little after adjustment for age and baseline CD4 count: 2.46 (95% CI: 1.57, 3.86). Change in CD4 count was similar for patients receiving vincristine monotherapy and bleomycin/vincristine (p?=?0.6). Conclusion Bleomycin/vincristine for the treatment of AIDS-associated KS was associated with better tumor response compared to vincristine monotherapy without impairing CD4 count recovery. Replication in larger datasets and randomized controlled trials is necessary.

Mwafongo, Albert A.; Rosenberg, Nora E.; Ng'ambi, Wingston; Werner, Alexandra B.; Garneau, William M.; Gumulira, Joe; Phiri, Sam; Hosseinipour, Mina C.

2014-01-01

208

Upregulation of the Saccharomyces cerevisiae efflux pump Tpo1 rescues an Imp2 transcription factor-deficient mutant from bleomycin toxicity.  

Science.gov (United States)

Yeast mutants lacking the transcriptional co-activator Imp2 are hypersensitive to the anticancer drug bleomycin, although the gene targets involved in this process remain elusive. A search for multicopy suppressors that rescue the imp2? mutant from bleomycin toxicity revealed the transcriptional activator Yap1, which can turn on many target genes such as transporters involved in regulating drug resistance. We show that YAP1 overexpression stimulated the expression of the TPO1 gene encoding a polyamine efflux pump, and that Yap1 failed to rescue the imp2? mutant from bleomycin toxicity in the absence of the TPO1 gene. Moreover, TPO1 overexpression, and not the related transporter gene QDR3, conferred upon the tpo1? imp2? double mutant parental resistance to bleomycin. We conclude that YAP1 overexpression rescues the imp2? mutant from bleomycin toxicity by triggering Tpo1 expression to expel the drug. Our data provide the first evidence that bleomycin could be a substrate for the Tpo1 efflux pump. Environ. Mol. Mutagen. 55:518-524, 2014. © 2014 Wiley Periodicals, Inc. PMID:24599794

Berra, Siham; Ayachi, Sami; Ramotar, Dindial

2014-07-01

209

Combined treatment of cervical cancer with bleomycin and high-dose rate intercavitary irradiation  

International Nuclear Information System (INIS)

Five of stage IIb 22 of stage IIIb and 9 of stage IV of cervical cancer patients, were treated with bleomycin (BLM) and irradiation. Of stage IIb and IV patients, there were no clinically significant differences between those treated by BLM and irradiation and by irradiation alone. Patients with stage IIIb cervical cancer who were treated with BLM and irradiation had better response to irradiation and longer remission period than those treated with irradiation alone. However, there was no difference in 5- years survival rate between these two groups. Patients with combined therapy had higher incidence rate of late intestinal complications by irradiation. The reason why many patients given combined therapy have late intestinal complication is discussed. (author)

1979-01-01

210

Effects of conformation radiotherapy combined with daily intramuscular injection of bleomycin for uterine cervical cancer  

International Nuclear Information System (INIS)

During the period 1970-1978, 112 fresh cervical cancer patients were treated with conformation radiotherapy (60Co ?-ray). Since 1973, 2mg of Bleomycin was injected intramuscularly about 30 minutes before the irradiation in 30 cases of them (i.e. BR-therapy). The comparative prognosis for each treatment method was investigated and the following results were obtained. 1) In Stage II and III cases the incidence of the local recurrence was reduced from 32.6% with conformation radiotherapy alone to 16.7% by BR-therapy. 2) The 5 year crude survival rate for Stage III patients was 31.8% in the former group and 50.0% in the latter group. This evidence supports the view that BR-therapy is an effective treatment for the carcinoma of the cervix. (author)

1980-01-01

211

"5"7Co-labelled bleomycin scintigraphy for the detection of lung cancer  

International Nuclear Information System (INIS)

The sensitivity and specificity of scanning with "5"7Co-labelled bleomycin for the diagnosis of lung cancer were determined from a prospective study involving a large group of patients with an abnormal chest roentgenogram. A semi-quantitative analysis of the scintigram was obtained by defining an index in terms of the excess isotope uptake within the tumour. Malignant pulmonary lesions were found in 121/175 patients and 113 had a positive scan. Benign pulmonary disorders were found in 54 patients, 45 of whom had a negative scan. The sensitivity and specificity were therefore 93% and 83% respectively. Bayes' theorem was then used to determine the predictive value of this test, either positive or negative, when the prevalence of disease varied from 10 to 90%. A receiver operating characteristic curve permits the choice of an appropriate value of the tumor uptake index to minimize the false positive fraction without classifying too many true positives as false negatives. (author)

1985-01-01

212

Effects of matrine on JAK-STAT signaling transduction pathways in bleomycin-induced pulmonary fibrosis.  

Science.gov (United States)

The current study aims to investigate the effects of matrine on the JAK-STAT signaling transduction pathways in bleomycin (BLM)-induced pulmonary fibrosis (PF) and to explore its action mechanism. A total of 72 male C57BL/6 mice were randomized into the control, model, and treatment groups. PF models were established by instilling BLM intratracheally. The treatment group was given daily matrine through gastric lavage. Six mice were sacrificed in each group at 3, 7, 14, and 28 days. The lung tissues were observed using hematoxylin-eosin staining. The expression of JAK, STAT1, and STAT3 was observed using immunohistochemistry and then determined using real-time polymerase chain reaction. Alveolitis and PF significantly improved in the treatment group compared with the model group (P Matrine exerts an anti-PF effect by inhibiting the JAK-STAT signaling transduction pathways. PMID:24146473

Ma, Xiuqin; Chen, Ruhua; Liu, Xiufang; Xie, Jin; Si, Keyun; Duan, Lirong

2013-01-01

213

EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-? signaling in lung fibroblasts  

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Full Text Available Abstract Background Fourteen-membered ring macrolides have been effective in reducing chronic airway inflammation and also preventing lung injury and fibrosis in bleomycin-challenged mice via anti-inflammatory effects. EM703 is a new derivative of erythromycin (EM without the bactericidal effects. We investigated the anti-inflammatory and antifibrotic effects of EM703 in an experimental model of bleomycin-induced lung injury and subsequent fibrosis in mice. Methods Seven-week-old male ICR mice were used. All experiments used eight mice/group, unless otherwise noted in the figure legends. Bleomycin was administered intravenously to the mice on day 0. EM703 was orally administered daily to mice. All groups were examined for cell populations in the bronchoalveolar lavage (BAL fluid and for induction of messenger RNA (mRNA of Smad3 and Smad4 in the lung tissues by reverse transcriptase (RT-polymerase chainreaction (PCR on day 7. Fibroblastic foci were assessed histologically, and the hydroxyproline content was chemically determined in the lung tissues on day 28. We performed assay of proliferation and soluble collagen production, and examined the induction of mRNA of Smad3 and Smad4 by RT-PCR in murine lung fibroblast cell line MLg2908. We also examined Smad3, Smad4 and phosphorylated Smad2/3 (p-Smad2/3 protein assay by western blotting in MLg2908. Results Bleomycin-induced lung fibrosis, and the infiltration of macrophages and neutrophils into the airspace were inhibited by EM703. The expression of Smad3 and Smad4 mRNA was clearly attenuated by bleomycin, but was recovered by EM703. EM703 also inhibited fibroblast proliferation and the collagen production in lung fibroblasts induced by Transforming growth factor-beta (TGF-?. The expression of Smad3 and Smad4 mRNA in murine lung fibroblasts disappeared due to TGF-?, but was recovered by EM703. EM703 inhibited the expression of p-Smad2/3 and Smad4 protein in murine lung fibroblasts induced by TGF-?. Conclusion These findings suggest that EM703 improves bleomycin-induced pulmonary fibrosis in mice by actions of anti-inflammation and regulation of TGF-? signaling in lung fibroblasts.

Inagaki Hirofumi

2006-01-01

214

Mineralocorticoid receptor antagonists attenuate pulmonary inflammation and bleomycin-evoked fibrosis in rodent models.  

Science.gov (United States)

Accumulating evidence indicates protective actions of mineralocorticoid antagonists (MR antagonists) on cardiovascular pathology, which includes blunting vascular inflammation and myocardial fibrosis. We examined the anti-inflammatory and anti-fibrotic potential of MR antagonists in rodent respiratory models. In an ovalbumin allergic and challenged Brown Norway rat model, the total cell count in nasal lavage was 29,348 ± 5451, which was blocked by spironolactone (0.3-60 mg/kg, p.o.) and eplerenone (0.3-30 mg/kg, p.o.). We also found that MR antagonists attenuated pulmonary inflammation in the Brown Norway rat. A series of experiments were conducted to determine the actions of MR blockade in acute/chronic lung injury models. (1) Ex vivo lung slice rat experiments found that eplerenone (0.01 and 10 µM) and spironolactone (10 µM) diminished lung hydroxyproline concentrations by 55 ± 5, 122 ± 9, and 83 ± 8%. (2) In in vivo studies, MR antagonists attenuated the increases in bronchioalveolar lavage (BAL) neutrophils and macrophages caused by lung bleomycin exposure. In separate studies, bleomycin (4.0 U/kg, i.t.) increased lung levels of hydroxyproline by approximately 155%, which was blocked by spironolactone (10-60 mg/kg, p.o.). In a rat Lipopolysaccharide (LPS) model, spironolactone inhibited acute increases in BAL cytokines with moderate effects on neutrophils. Finally, we found that chronic LPS exposure significantly increased end expiratory lung and decreased lung elastance in the mouse. These functional effects of chronic LPS were improved by MR antagonists. Our results demonstrate that MR antagonists have significant pharmacological actions in the respiratory system. PMID:24012780

Lieber, Gissela B; Fernandez, Xiomara; Mingo, Garfield G; Jia, Yanlin; Caniga, Michael; Gil, Malgorzata A; Keshwani, Shanil; Woodhouse, Janice D; Cicmil, Milenko; Moy, Lily Y; Kelly, Nancy; Jimenez, Johanna; Crawley, Yvette; Anthes, John C; Klappenbach, Joel; Ma, Yu-Lu; McLeod, Robbie L

2013-10-15

215

Protective effect of dexpanthenol on bleomycin-induced pulmonary fibrosis in rats.  

Science.gov (United States)

Despite extensive studies, there is no effective treatment currently available other than pirfenidone for idiopathic pulmonary fibrosis. A protective effect of pantothenic acid and its derivatives on cell damage produced by oxygen radicals has been reported, but it has not been tested in bleomycin (BLM)--induced pulmonary fibrosis in rats. Therefore, we aimed to investigate the preventive effect of dexpanthenol (Dxp) on pulmonary fibrosis. Thirty-two rats were assigned to four groups as follows: (1) control group, (2) dexpanthenol (Dxp) group; 500 mg/kg Dxp continued intraperitoneally for 14 days, (3) bleomycin (BLM) group; a single intratracheal injection of BLM (2.5 mg/kg body weight in 0.25-ml phosphate buffered saline), and (4) BLM + Dxp-treated group; 500 mg/kg Dxp was administered 1 h before the intratracheal BLM injection and continued for 14 days i.p. The histopathological grades of lung inflammation and collagen deposition, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and myeloperoxidase (MPO) were measured. BLM provoked inflammation and collagen deposition (p BLM reduced tissue activities of SOD, GPx, and CAT compared to controls (p = 0.01, 0.03, 0.009). MDA was increased with BLM (p = 0.003). SOD (p = 0.001) and MDA (p = 0.016) levels were improved in group 4. The CAT levels in the BLM + Dxp group were close to those in the control group (p > 0.05). We showed that Dxp significantly prevents BLM-induced lung fibrosis in rats. Further studies are required to evaluate the role of Dxp in the treatment of lung fibrosis. PMID:23995256

Ermis, Hilal; Parlakpinar, Hakan; Gulbas, Gazi; Vardi, Nigar; Polat, Alaadin; Cetin, Asli; Kilic, Talat; Aytemur, Zeynep Ayfer

2013-12-01

216

Discovery in PET/CT of an acute pulmonary toxicity with rapidly fatal bleomycin; Decouverte en TEP/TDM d'une toxicite pulmonaire aigue a la bleomycine rapidement fatale  

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Purpose: we report the case of a patient treated by chemotherapy for a Hodgkin disease showing after treatment an important pulmonary uptake that appears bilateral and symmetric on PET in connection with an acute toxicity at the preclinical stage. Conclusions: an intense and diffuse pulmonary uptake of the {sup 18}F.D.G. during the chemotherapy, including particularly the bleomycin, can reveal an acute serious pulmonary toxicity and potentially deadly at the pre-symptomatic stage. (N.C.)

Le Dortz, L.; Ben Fredj, M.; Lenoir, L.; Bahri, H.; Devillers, A.; Garin, E. [Centre Eugene-Marquis, Service de medecine nucleaire, 35 - Rennes (France)

2010-07-01

217

Assessment of the tumourigenic and metastatic properties of SK-MEL28 melanoma cells surviving electrochemotherapy with bleomycin  

Science.gov (United States)

Background Electrochemotherapy is a local treatment combining chemotherapy and electroporation and is highly effective treatment approach for subcutaneous tumours of various histologies. Contrary to surgery and radiation, the effect of electrochemotherapy on metastatic potential of tumour cells has not been extensively studied. The aim of the study was to evaluate the effect of electrochemotherapy with bleomycin on the metastatic potential of human melanoma cells in vitro. Materials and methods Viable cells 48 hours after electrochemotherapy were tested for their ability to migrate and invade through Matrigel coated porous membrane. In addition, microarray analysis and quantitative Real-Time PCR were used to detect changes in gene expression after electrochemotherapy. Results Cell migration and invasion were not changed in melanoma cells surviving electrochemotherapy. Interestingly, only a low number of tumourigenesis related genes was differentially expressed after electrochemotherapy. Conclusions Our data suggest that metastatic potential of human melanoma cells is not affected by electrochemotherapy with bleomycin, confirming safe role of electrochemotherapy in the clinics.

Todorovic, Vesna; Sersa, Gregor; Mlakar, Vid; Glavac, Damjan; Cemazar, Maja

2012-01-01

218

Nucleobase-Based Barbiturates: Their Protective Effect against DNA Damage Induced by Bleomycin-Iron, Antioxidant, and Lymphocyte Transformation Assay.  

Science.gov (United States)

A number of nucleobase-based barbiturates have been synthesized by combination of nucleic acid bases and heterocyclic amines and barbituric acid derivatives through green and efficient multicomponent route and one pot reaction. This approach was accomplished efficiently using aqueous medium to give the corresponding products in high yield. The newly synthesized compounds were characterized by spectral analysis (FT-IR, (1)H NMR, (13)C NMR, HMBC, and UV spectroscopy) and elemental analysis. Representative of all synthesized compounds was tested and evaluated for antioxidant, bleomycin-dependent DNA damage, and Lymphocyte Transformation studies. Compounds TBC > TBA > TBG showed highest lymphocyte transformation assay, TBC > TBA > BG showed inhibitory antioxidant activity using ABTS methods, and TBC > BPA > BAMT > TBA > 1, 3 -TBA manifested the best protective effect against DNA damage induced by bleomycin. PMID:24900997

Dhorajiya, Bhaveshkumar D; Dholakiya, Bharatkumar Z; Ibrahim, Ahmed S; Badria, Farid A

2014-01-01

219

Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores  

International Nuclear Information System (INIS)

Peroxisome proliferator-activated receptor-? (PPAR?) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPAR? agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

2012-08-01

220

Chemical activity of anticancer compounds : computational studies on the mechanism of bleomycin and the recognition of flavonoids  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The thesis is focused on the DNA-cleaving antibiotic bleomycin that is successfully used in the chemotherapy against several types of cancer like head and neck cancer or certain lymphomas and testicular cancer. Although it has been in use for more than two decades, the mechanism of its action is not known. Thus the harmful side effects are difficult to eliminate. On the other hand the process of design or improvement of pharmaceuticals is extremely complex and expensive. Therefore a new trend...

Karawajczyk, Anna

2007-01-01

 
 
 
 
221

Bleomycin Hydrolase Is Regulated Biphasically in a Differentiation- and Cytokine-dependent Manner: RELEVANCE TO ATOPIC DERMATITIS  

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Loss-of-function mutation in the profilaggrin gene is a major risk factor for atopic dermatitis (AD). Previously, we showed that a neutral cysteine protease, bleomycin hydrolase (BH), has a role in generating natural moisturizing factors, and calpain I is an upstream protease in the filaggrin degradation pathway. Here, we investigated the transcriptional regulatory mechanisms of BH and the relevance of BH to AD. First, we cloned the 5?-flanking region of BH. Deletion analyses identified a c...

2011-01-01

222

Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene.  

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Impaired fibrinolytic activity within the lung is a common manifestation of acute and chronic inflammatory lung diseases. Because the fibrinolytic system is active during repair processes that restore injured tissues to normal, reduced fibrinolytic activity may contribute to the subsequent development of pulmonary fibrosis. To examine the relationship between the fibrinolytic system and pulmonary fibrosis, lung inflammation was induced by bleomycin in transgenic mice that either overexpressed...

Eitzman, D. T.; Mccoy, R. D.; Zheng, X.; Fay, W. P.; Shen, T.; Ginsburg, D.; Simon, R. H.

1996-01-01

223

Mechanistic studies on bleomycin-mediated DNA damage: multiple binding modes can result in double-stranded DNA cleavage  

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The bleomycins (BLMs) are a family of natural glycopeptides used clinically as antitumor agents. In the presence of required cofactors (Fe2+ and O2), BLM causes both single-stranded (ss) and double-stranded (ds) DNA damage with the latter thought to be the major source of cytotoxicity. Previous biochemical and structural studies have demonstrated that BLM can mediate ss cleavage through multiple binding modes. However, our studies have suggested that ds cleavage occurs by partial intercalatio...

Chen, Jingyang; Ghorai, Manas K.; Kenney, Grace; Stubbe, Joanne

2008-01-01

224

Bleomycin exerts ambivalent antitumor immune effect by triggering both immunogenic cell death and proliferation of regulatory T cells.  

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Bleomycin (BLM) is an anticancer drug currently used for the treatment of testis cancer and Hodgkin lymphoma. This drug triggers cancer cell death via its capacity to generate radical oxygen species (ROS). However, the putative contribution of anticancer immune responses to the efficacy of BLM has not been evaluated. We make here the observation that BLM induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surfac...

Bugaut, He?le?ne; Bruchard, Me?lanie; Berger, He?le?ne; Derange?re, Valentin; Odoul, Ludivine; Euvrard, Romain; Ladoire, Sylvain; Chalmin, Fanny; Ve?gran, Fre?de?rique; Re?be?, Ce?dric; Apetoh, Lionel; Ghiringhelli, Franc?ois; Mignot, Gre?goire

2013-01-01

225

Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumour cells: I. In vitro cytotoxicity.  

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Evidence in the literature suggests that hyperthermia (HT) or inhibitors of calmodulin can increase the sensitivity of rodent cells to bleomycin (BLM) by interfering with DNA repair functions. In an attempt to explore methods of improving the efficacy of thermochemotherapy we have investigated the individual and combined effects of HT (44 degrees C) and the calmodulin inhibitor trifluoperazine (TFP, 30 micrograms ml-1) on early plateau phase monolayer cultures of mouse EMT6 tumour cells for s...

Mircheva, J.; Smith, P. J.; Bleehen, N. M.

1986-01-01

226

Bleomycin Exerts Ambivalent Antitumor Immune Effect by Triggering Both Immunogenic Cell Death and Proliferation of Regulatory T Cells  

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Bleomycin (BLM) is an anticancer drug currently used for the treatment of testis cancer and Hodgkin lymphoma. This drug triggers cancer cell death via its capacity to generate radical oxygen species (ROS). However, the putative contribution of anticancer immune responses to the efficacy of BLM has not been evaluated. We make here the observation that BLM induces immunogenic cell death. In particular, BLM is able to induce ROS-mediated reticulum stress and autophagy, which result in the surfac...

Bugaut, He?le?ne; Bruchard, Me?lanie; Berger, He?le?ne; Derange?re, Valentin; Odoul, Ludivine; Euvrard, Romain; Ladoire, Sylvain; Chalmin, Fanny; Ve?gran, Fre?de?rique; Re?be?, Ce?dric; Apetoh, Lionel; Ghiringhelli, Franc?ois; Mignot, Gre?goire

2013-01-01

227

Calcium electroporation in three cell lines; a comparison of bleomycin and calcium, calcium compounds, and pulsing conditions  

DEFF Research Database (Denmark)

Electroporation with calcium (calcium electroporation) can induce ATP depletion-associated cellular death. In the clinical setting, the cytotoxic drug bleomycin is currently used with electroporation (electrochemotherapy) for palliative treatment of tumors. Calcium electroporation offers several advantages over standard treatment options: calcium is inexpensive and may readily be applied without special precautions, as is the case with cytostatic drugs. Therefore, details on the use of calcium electroporation are essential for carrying out clinical trials comparing calcium electroporation and electrochemotherapy.

Frandsen, Stine Krog; Gissel, Hanne

2013-01-01

228

Boswellic acids extract attenuates pulmonary fibrosis induced by bleomycin and oxidative stress from gamma irradiation in rats  

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Abstract Background Interstitial pulmonary fibrosis is characterized by an altered cellular composition of the alveolar region with excessive deposition of collagen. Lung inflammation is also common in pulmonary fibrosis. This study aims to test the inhibition of 5-lipooxygenase (5-LOX) by boswellic acid (BA) extract in an experimental model of pulmonary fibrosis using bleomycin (BL). Methods Boswellic acid extract (1 g/kg) was force-fed to rats seven days prior...

Ali Eman; Mansour Somaya

2011-01-01

229

Diethylpyrocarbonate and permanganate provide evidence for an unusual DNA conformation induced by binding of the antitumour antibiotics bleomycin and phleomycin.  

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DNA structural changes induced by bleomycin have been investigated using diethylpyrocarbonate and permanganate as probes under conditions in which the antibiotic binds to, but does not cut the DNA. Diethyl-pyrocarbonate shows an enhanced reaction with adenines in the presence of the antibiotic in the sequences GTA greater than GCA greater than GAA, on the 3' side of the drug cutting site (GPy). Permanganate ions display an enhanced reactivity at the second pyrimidine of the sequence GPyPy. Th...

Fox, K. R.; Grigg, G. W.

1988-01-01

230

The Biosynthetic Gene Cluster of Zorbamycin, a Member of the Bleomycin Family of Antitumor Antibiotics, from Streptomyces flavoviridis ATCC 21892  

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The biosynthetic gene cluster for the glycopeptide-derived antitumor antibiotic zorbamycin (ZBM) was cloned by screening a cosmid library of Streptomyces flavoviridis ATCC 21892. Sequence analysis revealed 40 ORFs belonging to the ZBM biosynthetic gene cluster. However, only 23 and 22 ORFs showed striking similarities to the biosynthetic gene clusters for the bleomycins (BLMs) and tallysomycins (TLMs), respectively; the remaining ORFs do not show significant homology to ORFs from the related ...

2009-01-01

231

Sprague Dawley response to the cyclophosphamide and bleomycin in the alkaline comet assay of peripheral blood leukocytes  

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Full Text Available In this article we decide to evaluate genotoxic effect of the cyclophosphamide and bleomycin in the individual cells by means of alkaline comet assay using the Sprague Dawley rats in both sexes as experimental biomodel. Which were formed 5 experimental groups per sex, the first administered with NaCl 0,9 % by intraperitoneal (i.p route, the second and third groups were administered with cyclophosphamide by i.p route, with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 40 mg/kg. At the end of the experience bigger induction of damage was obtained with the use of the cyclophosphamide and bleomycin, both in the design of 48 and 24 hours administration before the sacrifice. This constitutes under our experimental conditions the two better experimental designs to induce the strand breaks (SB or alkali-labile sites formation on DNA, increasing considerably the frequency spontaneous present in this species of rat, being useful in studies of drugs evaluation that they have not been explored in to the in vivo antigenotoxicity and genotoxicity environment.

Daniel Francisco Arencibia Arrebola

2010-06-01

232

Place occupied by gallium 67 citrate and 57Co-bleomycine scintigraphy in the evaluation and supervision of cancers  

International Nuclear Information System (INIS)

This work attempts to situate 57Co-bleomycine and gallium67 citrate scintigraphy in pre-treatment evaluation and supervision of solid tumours or malignant lymphomas. The results given by these two radiopharmaceuticals are compared for a series of 136 patients and a bibliograhical survey covering more than 3.000 cases is compiled. The purpose of the study is to establish the diagnostic capacity of each of these two tumoral tracers, according to the nature and location of the lesions, and, on this basis, to try to estimate the position it occupies as well as its indications and limits. The following are dealt with successively: - the biological properties, development of labelling techniques and tumoral fixation mechanisms of 57Co-bleomycine and 67Ga citrate reviewed historically. - The physical and technological foundations of the scintigraphic methods used. - The results obtained with 57Co bleomycine and 67Ga citrate in patients carrying solid tumours and malignant lymphomas. In the discussion these two radiotracers are compared as a function of the histological nature and location of the lesions. Finally these two isotopic methods are situated with respect to other complementary examinations and from this their indications and limits are inferred

1978-01-01

233

Adaptation of TURN protocol to SIP protocol  

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Full Text Available Today, SIP is a protocol par Excellence in the field of communication over Internet. But, the fact that it belongs to the application layer constitutes a weakness vis-a-vis the NAT traversal. This weakness is due to the way in which the server replies to the requests of clients on the one hand. On the other, it is caused by the dynamic allocation of UDP ports for emission and reception of packets RTP/RTCP. The TURN Protocol may face this weakness. However, its use requires a certain number of exchanges between the clients and a TURN server before establishing the multimedia sessions and this increase the latent time. In this article, we propose to adapt TURN protocol for applications based on SIP protocol such as telephony over Internet, conference video, etc. This adaptation optimises the establishment of multimedia sessions by integrating a manager of TCP connections and multimedia flow controller into SIP Proxy server.

Mokhtar Keche

2010-01-01

234

Adaptation of TURN protocol to SIP protocol  

CERN Multimedia

Today, SIP is a protocol par Excellence in the field of communication over Internet. But, the fact that it belongs to the application layer constitutes a weakness vis-a-vis the NAT traversal. This weakness is due to the way in which the server replies to the requests of clients on the one hand. On the other, it is caused by the dynamic allocation of UDP ports for emission and reception of packets RTP/RTCP. The TURN Protocol may face this weakness. However, its use requires a certain number of exchanges between the clients and a TURN server before establishing the multimedia sessions and this increase the latent time. In this article, we propose to adapt TURN protocol for applications based on SIP protocol such as telephony over Internet, conference video, etc. This adaptation optimises the establishment of multimedia sessions by integrating a manager of TCP connections and multimedia flow controller into SIP Proxy server.

Guezouri, Mustapha; Keche, Mokhtar

2010-01-01

235

Modeling Transport Layer Protocols  

Science.gov (United States)

In a layered communication architecture, transport layer protocols handle the data exchange between processes on different hosts over potentially lossy communication channels. Typically, transport layer protocols are either connection-oriented or are based on the transmission of individual datagrams. Well known transport protocols are the connection-oriented Transmission Control Protocol (TCP) [372] and the User Datagram Protocol (UDP) [370] as well as the Stream Control Transmission Protocol (SCTP) [340] and DCCP, the Datagram Congestion Control Protocol [259]. In this chapter, we focus on the modeling process of the transport layer. While we mostly use TCP and UDP as a base of comparison from this point, we emphasize that the methodologies discussed further on are conferrable to virtually any transport layer in any layered communication architecture.

Sasnauskas, Raimondas; Weingaertner, Elias

236

A young male with shortness of breath  

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Full Text Available We report a case of primary mediastinal seminoma, which presented initially with shortness of breath and a swelling in upper part of anterior chest wall. The diagnosis of primary mediastinal seminoma was established on the basis of histologic findings and was confirmed by immunohistochemical analysis. Abdominal, pelvis and cerebral CT scan, testicular ultrasound and TC-99 MDP bone scintigraphy were negative. Chemotherapy was initiated with B.E.P. protocol (Bleomycin, Etoposide, Cisplatinum; the patient received four cycles of chemotherapy. After 8 months, the patient was seen in the clinic; he was well.

Khan Fahmi

2008-01-01

237

Effects of phosphodiesterase 4 inhibition on bleomycin-induced pulmonary fibrosis in mice  

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Full Text Available Abstract Background Pulmonary fibrosis (PF is a group of devastating and largely irreversible diseases. Phosphodiesterase (PDE 4 is involved in the processes of remodeling and inflammation, which play key role in tissue fibrosis. The aim of the study was, therefore, to investigate the effect of PDE4 inhibition in experimental model of PF. Methods PF was induced in C57BL/6N mice by instillation of bleomycin. Pharmacological inhibition of PDE4 was achieved by using cilomilast, a selective PDE4 inhibitor. Changes in either lung inflammation or remodeling were evaluated at different stages of experimental PF. Lung inflammation was assessed by bronchoalveolar lavage fluid (BALF differential cell count and reverse transcription quantitative polymerase chain reaction (RT-qPCR for inflammatory cytokines. Changes in tissue remodeling were evaluated by pulmonary compliance measurement, quantified pathological examination, measurement of collagen deposition and RT-qPCR for late remodeling markers. Survival in all groups was analyzed as well. Results PDE4 inhibition significantly reduced the total number of alveolar inflammatory cells in BALF of mice with bleomycin-induced PF at early fibrosis stage (days 4 and 7. Number of macrophages and lymphocytes, but not neutrophils, was significantly reduced as well. Treatment decreased lung tumor necrosis factor (TNF-? mRNA level and increased mRNA level of interleukin (IL-6 but did not influence IL-1?. At later stage (days 14 and 24 cilomilast improved lung function, which was shown by increase in lung compliance. It also lowered fibrosis degree, as was shown by quantified pathological examination of Hematoxilin-Eosin stained lung sections. Cilomilast had no significant effect on the expression of late remodeling markers such as transforming growth factor (TGF-?1 and collagen type Ia1 (COL(I?1. However, it tended to restore the level of lung collagen, assessed by SIRCOL assay and Masson's trichrome staining, and to improve the overall survival. Conclusions Selective PDE4 inhibition suppresses early inflammatory stage and attenuates the late stage of experimental pulmonary fibrosis.

Ghofrani Hossein A

2010-05-01

238

Pulmonary fate of [3H]bleomycin A2 in mice  

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The pulmonary fate of radiolabeled bleomycin [S-methyl-3H]bleomycin A2 ([3H]BLM A2) was studied in mice after intratracheal (i.t.) or s.c. injection. The loss of radioactivity from the lungs followed apparent first-order kinetics during the first 3 hr after i.t. drug instillation with a half-time of removal of 32 min. In addition, the initial pulmonary removal was linear with instilled doses ranging from 0.02 to 2.2 mg/kg. Radioactivity was detected in liver, kidneys, spleen and serum 1 hr after i.t. administration. Approximately 1% of the i.t. administered dose was detected in the lungs after 24 hr, indicating that the rate of removal of radioactivity slowed between 3 and 24 hr after i.t. drug instillation. Eighty percent of the radioactivity found in the lungs 1 hr after i.t. instillation was unmetabolized [3H]BLM A2, but by 24 hr less than 25% was unmetabolized drug and almost 40% was the nonfibrogenic metabolite, desamidobleomycin A2. After s.c. administration of 10 mg/kg of [3H]BLM A2, peak pulmonary levels were observed between 45 and 60 min and were less than 1% of the injected dose. Pulmonary levels comparable to those seen with a single fibrogenic i.t. dose (2.2 mg/kg) could not be obtained after a s.c. injection even with a toxic dose of the drug (100 mg/kg). In addition, twice weekly s.c. injections of unlabeled BLM A2 (10 mg/kg) for 5 weeks did not alter the amount of radioactivity seen in the lungs after a s.c. injection of [3H]BLM A2. Thus, the pulmonary fibrosis seen with i.t. BLM administration may reflect the high initial content of unmetabolized drug achieved in the lungs

1984-01-01

239

CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin-induced scleroderma.  

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Mice subcutaneously injected with bleomycin, in an experimental model of human systemic sclerosis, develop cutaneous and lung fibrosis with autoantibody production. CD19 is a general "rheostat" that defines signaling thresholds critical for humoral immune responses, autoimmunity, and cytokine production. To determine the role of CD19 in the bleomycin-induced systemic sclerosis model, we investigated the development of fibrosis and autoimmunity in CD19-deficient mice. Bleomycin-treated wild-type mice exhibited dermal and lung fibrosis, hyper-gamma-globulinemia, autoantibody production, and enhanced serum and skin expression of various cytokines, including fibrogenic interleukin-4, interleukin-6, and transforming growth factor-beta1, all of which were inhibited by CD19 deficiency. Bleomycin treatment enhanced hyaluronan production in the skin, lung, and sera. Addition of hyaluronan, an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4, stimulated B cells to produce various cytokines, primarily through TLR4; CD19 deficiency suppressed this stimulation. These results suggest that bleomycin induces fibrosis by enhancing hyaluronan production, which activates B cells to produce fibrogenic cytokines mainly via TLR4 and induce autoantibody production, and that CD19 deficiency suppresses fibrosis and autoantibody production by inhibiting TLR4 signals. PMID:18467694

Yoshizaki, Ayumi; Iwata, Yohei; Komura, Kazuhiro; Ogawa, Fumihide; Hara, Toshihide; Muroi, Eiji; Takenaka, Motoi; Shimizu, Kazuhiro; Hasegawa, Minoru; Fujimoto, Manabu; Tedder, Thomas F; Sato, Shinichi

2008-06-01

240

Radiotherapy and bleomycin-containing chemotherapy in the treatment of advanced head and neck cancer: report of six patients and review of the literature  

International Nuclear Information System (INIS)

In an effort to improve the complete remission rate achievable with bleomycin and cisplatin, administered prior to radiotherapy in previously untreated patients with unresectable epidermoid carcinoma of the head and neck, we initiated a pilot study employing simultaneous chemotherapy and radiotherapy. Six patients were treated with bleomycin (B) 15 mg i.m. t.i.w. 30-60 minutes prior to radiotherapy (RT) treatment with conventional fractionation, 180-200 rad/fx, 5 fx/week. During interruptions in B + RT for healing of mucocutaneous reactions, patients received cisplatin 40 mg/mg m2 once weekly. Toxicity included severe mucositis within the radiation port in all patients, three episodes of infection, and significant myelosuppression in one patient. Transient mild serum creatinine elevation occurred in four patients. Three patients did not complete treatment because of severity of toxicity. Response was: primary--4/6CR, 1/6 PR; regional nodes--1/5 CR, 4/5 PR. Review of the literature of concurrent bleomycin and radiotherapy trials in head and neck cancer indicates that other investigators have encountered severe toxicity using bleomycin dose and radiation fractionation schedules similar to ours. Toxicity may be reduced when lower doses of concurrent bleomycin and/or alternative radiation fractionation schedules are employed. Although results of uncontrolled trials suggest a possible therapeutic advantage to treatment with the combination compared to radiotherapy alone, this has not clearly been established in the four randomized trials reviewed

1981-01-01

 
 
 
 
241

Point- To- Point Protocol  

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Full Text Available The telephone line provides a physical link, but to control and manage the transfer of data, there is a need for point-to-point connection. The first protocol devised for this purpose was serial line internet protocol (SLIP. However, SLIP has some deficiencies: it does not support protocols other than internet protocol (IP. It does not allow the IP addresses to be assigned dynamically, and it does not support authentication of the user. The POINT-TO-POINT (PPP is a protocol designed to respond to respond to the deficiencies. Today the PPP protocol standard finds wide use in asynchronous and synchronous connections between computers, bridges, routers and other intermediate devices.PPP is gaining acceptance as a standard for Integrated Services Digital Network(ISDN, and many implementations of X.25 also support PPP connection.

Immadisetty L V Chandrika,

2012-11-01

242

Security of RFID protocols  

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Radio-frequency identification (RFID) is a technology that uses radio waves to exchange data between RFID readers and tags. The low manufacturing costs and small size and the lack of need of a power source make RFID tags useful in many applications, but also impose a strong need for secure RFID protocols. The first part of this thesis considers the analysis of untraceability of RFID protocols. We start by designing a formal syntax and semantics for security protocols. We define untraceab...

Deursen, Ton

2011-01-01

243

Malformaciones linfáticas: tratamiento percutáneo con bleomicina / Lymphatic malformations: percutaneus treatment with bleomycin  

Scientific Electronic Library Online (English)

Full Text Available SciELO Argentina | Language: Spanish Abstract in spanish Las malformaciones linfáticas son anomalías del desarrollo del sistema linfático que tienden a sufrir complicaciones en su evolución. En la última década, la terapia con agentes esclerosantes ha ido ganando popularidad sobre la cirugía, por su eficacia, sus menores complicaciones y sus excelentes re [...] sultados estéticos. Presentamos una serie de 24 pacientes tratados mediante esclerosis percutánea con bleomicina. Los resultados fueron excelentes (reducción de volumen ? 95% y asintomáticos) en 12 pacientes, buenos (reducción de volumen entre 50% y 95% y asintomáticos) en 5 pacientes, regulares (reducción de volumen Abstract in english Lymphatic malformations are developmental abnormalities of the lymphatic system, which tend to complicate during their evolution. In the last decade, therapy with sclerosing agents has gained popularity over surgery due to its effectiveness, fewer complications, and excellent cosmetic results. We pr [...] esent a series of 24 patients treated with percutaneous bleomycin injection. Results were excellent (volume reduction ? 95%, without symptoms) in 12 patients, good (volume reduction between 50% and 95%, without symptoms) in 5 patients, fair (volume reduction

José Luis, Cuervo; Eduardo, Galli; Guillermo, Eisele; Erica, Johannes; Alejandro, Fainboim; Silvia, Tonini; Walter, Joaquin; Bettina, Viola; Miguel, Nazar.

244

Bleomycin-induced apoptosis of alveolar epithelial cells requires angiotensin synthesis de novo.  

Science.gov (United States)

Primary cultures of rat type II alveolar epithelial cells (AECs) or human AEC-derived A549 cells, when exposed to bleomycin (Bleo), exhibited concentration-dependent apoptosis detected by altered nuclear morphology, fragmentation of DNA, activation of caspase-3, and net cell loss over time. In both cell culture models, exposure to Bleo caused time-dependent increases in angiotensinogen (ANGEN) mRNA. Antisense oligonucleotides against ANGEN mRNA inhibited Bleo-induced apoptosis of rat AEC or A549 cells by 83 and 84%, respectively (P < 0.01 and P < 0.05), and prevented Bleo-induced net cell loss. Apoptosis of rat AECs or A549 cells in response to Bleo was inhibited 91% by the ANG-converting enzyme inhibitor captopril or 82%, respectively, by neutralizing antibodies specific for ANG II (both P < 0.01). Antagonists of ANG receptor AT(1) (losartan, L-158809, or saralasin), but not an AT(2)-selective blocker (PD-123319), inhibited Bleo-induced apoptosis of either rat AECs (79%, P < 0.01) or A549 cells (83%, P < 0.01) and also reduced the activity of caspase-3 by 52% (P < 0.05). These data indicate that Bleo, like Fas(L) or TNF-alpha, induces transactivation of ANG synthesis de novo that is required for AEC apoptosis. They also support the theory that ANG system antagonists have potential for the blockade of AEC apoptosis in situ. PMID:12573988

Li, Xiaopeng; Zhang, Huiying; Soledad-Conrad, Valerie; Zhuang, Jiaju; Uhal, Bruce D

2003-03-01

245

Characterization of the bleomycin resistance determinant encoded on the transposon Tn5.  

Science.gov (United States)

The transposon Tn5 carries a gene, ble, which confers resistance to bleomycin (Bm) and gives a survival advantage to its host cell. We found that the ble gene product, designated BLMT, is a binding protein with a strong affinity for Bm. BLMT quenched both the antibacterial and DNA-cleaving activities of Bm, when incubated with the antibiotic. An electron spin resonance spin-trapping analysis showed that BLMT inhibits the generation of Bm-induced hydroxyl radical, by trapping Bm but not the hydroxyl radical. Western blot analysis using an anti-BLMT monoclonal antibody revealed that BLMT is immunologically distinct from Bm-binding proteins from Streptomyces verticillus, Staphylococcus aureus and Streptoalloteichus hindustanus. Escherichia coli, transformed with a mutant ble having leucine instead of proline at N-terminal amino acid position 7, lost resistance to Bm, although the cell maintained the survival benefit. This suggests that the Bm resistance mediated by ble is independent of its ability to give a survival advantage to the host bacterium. PMID:9923599

Kumagai, T; Nakano, T; Maruyama, M; Mochizuki, H; Sugiyama, M

1999-01-01

246

Cytotoxic activity, tumor accumulation, and tissue distribution of ruthenium-103-labeled bleomycin  

International Nuclear Information System (INIS)

Bleomycin (BLM) was labeled with gamma-emitting 103Ru. Yields of 103Ru-labeled BLM as high as 50.6% were attained. 103Ru-labeled BLM was stable in vitro and the 103ru label was not displaced by large excesses of Cu (II) and Co (II) or Fe (III). Chromatography of the urine following 103Ru-labeled BLM injection indicated no in vivo decomposition. Pharmacokinetic studies in healthy inbred SD and tumor-bearing inbred BUF rats demonstrated tumor accumulations, tissue distributions, and clearance nearly identical with those reported for 3H-labeled BLM. Cytotoxicity studies on a WI-L2 human B-cell line showed that BLM labeled with nonradioactive Ru retained 100% of the activity demonstrated by native BLM. Thus BLM may be labeled with isotopes of Ru to form stable complexes by a simple, rapid reaction without loss of its chemotherapeutic properties or variations in its in vivo distribution. BLM labeled with the proper Ru isotope should prove useful as a gamma-emitting tracer for BLM or a beta-emitting compound capable of providing combination chemotherapy and radiotherapy of tumors

1981-01-01

247

Attenuation of lung inflammation and fibrosis in CD69-deficient mice after intratracheal bleomycin  

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Full Text Available Abstract Background Cluster of differentiation 69 (CD69, an early activation marker antigen on T and B cells, is also expressed on activated macrophages and neutrophils, suggesting that CD69 may play a role in inflammatory diseases. To determine the effect of CD69 deficiency on bleomycin(BLM-induced lung injury, we evaluated the inflammatory response following intratracheal BLM administration and the subsequent fibrotic changes in wild type (WT and CD69-deficient (CD69-/- mice. Methods The mice received a single dose of 3 mg/kg body weight of BLM and were sacrificed at 7 or 14 days post-instillation (dpi. Lung inflammation in the acute phase (7 dpi was investigated by differential cell counts and cytokine array analyses of bronchoalveolar lavage fluid. In addition, lung fibrotic changes were evaluated at 14 dpi by histopathology and collagen assays. We also used reverse transcription polymerase chain reaction to measure the mRNA expression level of transforming growth factor ?1 (TGF-?1 in the lungs of BLM-treated mice. Results CD69-/- mice exhibited less lung damage than WT mice, as shown by reductions in the following indices: (1 loss of body weight, (2 wet/dry ratio of lung, (3 cytokine levels in BALF, (4 histological evidence of lung injury, (5 lung collagen deposition, and (6 TGF-?1 mRNA expression in the lung. Conclusion The present study clearly demonstrates that CD69 plays an important role in the progression of lung injury induced by BLM.

Matsunaga Hirofumi

2011-10-01

248

Blockade of advanced glycation end product formation attenuates bleomycin-induced pulmonary fibrosis in rats  

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Full Text Available Abstract Background Advanced glycation end products (AGEs have been proposed to be involved in pulmonary fibrosis, but its role in this process has not been fully understood. To investigate the role of AGE formation in pulmonary fibrosis, we used a bleomycin (BLM-stimulated rat model treated with aminoguanidine (AG, a crosslink inhibitor of AGE formation. Methods Rats were intratracheally instilled with BLM (5 mg/kg and orally administered with AG (40, 80, 120 mg/kg once daily for two weeks. AGEs level in lung tissue was determined by ELISA and pulmonary fibrosis was evaluated by Ashcroft score and hydroxyproline assay. The expression of heat shock protein 47 (HSP47, a collagen specific molecular chaperone, was measured with RT-PCR and Western blot. Moreover, TGF?1 and its downstream Smad proteins were analyzed by Western blot. Results AGEs level in rat lungs, as well as lung hydroxyproline content and Ashcroft score, was significantly enhanced by BLM stimulation, which was abrogated by AG treatment. BLM significantly increased the expression of HSP47 mRNA and protein in lung tissues, and AG treatment markedly decreased BLM-induced HSP47 expression in a dose-dependent manner (p Conclusion These findings suggest AGE formation may participate in the process of BLM-induced pulmonary fibrosis, and blockade of AGE formation by AG treatment attenuates BLM-induced pulmonary fibrosis in rats, which is implicated in inhibition of HSP47 expression and TGF?/Smads signaling.

Liu Dai-Shun

2009-06-01

249

Vesnarinone Represses the Fibrotic Changes in Murine Lung Injury Induced by Bleomycin  

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Full Text Available We investigated the potential usefulness of vesnarinone, a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM-induced pulmonary fibrosis. Mice were fed a control diet (n=42, or a diet containing low (n=42 or high (n=42 dose of vesnarinone. Dietary intake of vesnarinone minimized the BLM toxicity as reflected by significant decreases in numbers of inflammatory cells, KC, and soluble TNF receptors in the bronchoalveolar lavage fluid. A quantitative evaluation of histology demonstrated significantly mild lung parenchymal lesions in BLM-treated mice fed with diet containing high dose of vesnarinone than in the control diet group. Consistent with the histopathology, hydroxyproline levels in lung tissue from BLM-treated mice fed with diet containing vesnarinone were significantly lower than that from mice fed with control diet. We concluded that vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase.

Minoru Inage, Hidenori Nakamura, Hiroshi Saito, Shuichi Abe, Toshihiko Hino, Noriaki Takabatake, Kyoko Terashita, Manabu Ogura, Shuichi Kato, Tetsumi Hosokawa, Makoto Sata, Hitonobu Tomoike

2009-01-01

250

Treatment of orbital venous malformations with intralesional injection of bleomycin lipiodol emulsion  

International Nuclear Information System (INIS)

Objective: To evaluate the efficacy and safety of intralesional injection with bleomycin lipiodol emulsion (BLE) for the treatment of orbital venous malformation (OVM). Methods: There were 15 cases with left- sided OVM (n=9 ) and right- sided OVM (n=6). All patients had proptosis. The pr optosis was less than 5 mm in 11 cases, >5 mm and ?8 mm in 4 cases. The mean value was 4.2 mm. Four patients noticed reduction in their vision and two had diplopia. Those patients were examined by CT or MR. Direct venography was performed in each patient. After the diagnosis of OVM was confirmed, intralesional injection of BLE was performed. The efficacy of the treatment and complications were observed during the following 8 to 42 months (mean 23 months). Results: The BLE were successfully injected in all the patients. All patients had resolution of proptosis and diplopia. Three patients gained improvement of visual acuity. The periorbital swelling occurred in all patients after operation and resolved within 1 week without special treatment. Other complications, such as orbital hemorrhage and periorbital scar, were not observed during following-up. Conclusion: Intralesional injection with BLE is convenient, safe and efficient for the treatment of OVM. (authors)

2007-10-01

251

Combined cytogenotoxic effects of bee venom and bleomycin on rat lymphocytes: an in vitro study.  

Science.gov (United States)

This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV) and/or the chemotherapeutic agent bleomycin (BLM) on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20 ?g/mL respectively for 24 and 72 hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2). The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity. PMID:24822179

Abd-Elhakim, Yasmina M; Khalil, Samah R; Awad, Ashraf; Al-Ayadhi, Laila Y

2014-01-01

252

Effects of combined treatment with radiation and bleomycin on the oral carcinoma involving the mandible  

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The effect of concurrent combined treatment with 22.5 Gy of radiation and 110 mg of bleomycin or 55 mg of peplomycin on oral carcinoma involving the mandible was examined histologically. In 14 of 18 patients who had mandibles resected after this combined treatment, bone invasion by carcinoma was observed histologically. According to Shimosato's classification of histological effects, 3 belonged to Grade III/IV, 4 to IIb, 3 to IIa and 4 to I. The formation of new bone that was considered to be reparable was observed in the marked effective patients. In 4 patients the Grade IIb, residual surviving cancer cells were observed in the mandible. Accordingly, excision was needed in the area of radiologic features of mandibular infiltration. But it is considered that although the excision scope for the patient who has received the preoperative treatment is the same as that for the patient who has not, it is advantageous for the former patient that a wider safety region is obtained.

Okamoto, Manabu; Ozeki, Satoru; Higuchi, Yoshinori; Tashiro, Hideo

1988-07-01

253

Combined Cytogenotoxic Effects of Bee Venom and Bleomycin on Rat Lymphocytes: An In Vitro Study  

Science.gov (United States)

This study was carried out to determine the cytotoxic and genotoxic effects of bee venom (BV) and/or the chemotherapeutic agent bleomycin (BLM) on healthy isolated rat lymphocytes utilizing morphometric and molecular techniques. Using the Ficoll-Histopaque density gradient centrifugation technique, lymphocytes were isolated, divided into groups, and subjected to BV and/or BLM at incubation medium concentrations of 10 or 20??g/mL respectively for 24 and 72?hrs. An MTT assay and fluorescent microscopy examinations were used to assess the cytotoxic effects. To determine the predominant type of BV and/or BLM-induced cell death, LDH release assay was employed beside quantitative expression analyses of the apoptosis-related genes (Caspase-3 and Bcl-2). The genotoxic effects of the tested compounds were evaluated via DNA fragmentation assay. The results of these assays demonstrated that BV potentiates BLM-induced cytotoxicity through increased LDH release and diminished cell viability. Nevertheless, BV significantly inhibited the BLM-induced DNA damage. The results verify that BV significantly attenuates the genotoxic effects of BLM on noncancerous isolated rat lymphocytes but does not diminish BLM cytotoxicity.

Abd-Elhakim, Yasmina M.; Khalil, Samah R.; Awad, Ashraf; AL-Ayadhi, Laila Y.

2014-01-01

254

Angiotensin II type 2 receptor antagonist reduces bleomycin-induced pulmonary fibrosis in mice  

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Full Text Available Abstract Background The role of angiotensin II type 2 receptor (AT2 in pulmonary fibrosis is unknown. To evaluate the influence of angiotensin II type 1 receptor (AT1 and AT2 antagonists in a mouse model of bleomycin (BLM-induced pulmonary fibrosis. Methods We examined effects of the AT1 antagonist (AT1A olmesartan medoxomil (olmesartan and the AT2 antagonist (AT2A PD-123319 on BLM-induced pulmonary fibrosis, which was evaluated by Ashcroft's pathological scoring and hydroxyproline content of lungs. We also analyzed the cellular composition and cytokine levels in bronchoalveolar lavage fluid (BALF. Results With olmesartan, the lung fibrosis score and hydroxyproline level were significantly reduced, and lymphocyte and neutrophil counts and tumor necrosis factor (TNF-? levels in BALF were reduced on day 7. On day 14, macrophage and lymphocyte counts in BALF were reduced, accompanied by a reduction in the level of transforming growth factor (TGF-?1. With PD-123319, the lung fibrosis score and hydroxyproline level were reduced. On day 7, macrophage, lymphocyte, and neutrophil counts in BALF were reduced, accompanied by reductions in TNF-? and monocyte chemoattractant protein (MCP-1 levels. On day 14, macrophage, lymphocyte, and neutrophil counts in BALF were also reduced, accompanied by a reduction in the level of macrophage inflammatory protein (MIP-2 level but not TGF-?1. Conclusion Both AT1 and AT2 are involved in promoting interstitial pneumonia and pulmonary fibrosis via different mechanisms of action.

Tagami Atsuro

2008-05-01

255

Role in cancer therapy of inhibiting recovery from PLD induced by radiation or bleomycin  

International Nuclear Information System (INIS)

Effects on survival of allowing and inhibiting potentially lethal damage recovery (PLDR) after x ray or bleomycin (bleo) exposure, especially at clinically applicable doses, were examined in plateau phase Chinese hamster ovary (CHO) cells. Dose modifying factors (DMF's) at doses used clinically (1-4 Gy) were more than 2.0, suggesting its importance in radiotherapy of cancers. Among the inhibitors tested, 3'-deoxyguanosine at 3.7 mM and caffeine at 10.3 mM inhibited x and bleo PLDR (DMF of 1.0-1.2) when trypsinized 24 hours after treatment. However, interestingly, 3 aminobenzamide, a specific inhibitor of poly (ADP) ribose synthesis, even at 14.7 or 29.4 mM, was not as effective in suppressing both x and bleo PLDR, suggesting the role of repair processes independent of poly (ADP) ribose levels in PLDR in plateau phase cultures. Possibilities of clinical application of PLDR inhibitors as radio- and chemosensitizers are discussed

1984-01-01

256

Intratumoral injection of 5-fluorouracil and bleomycin for inoperable cancer in the cardioesophageal region  

International Nuclear Information System (INIS)

The methods and results of combined therapy (drugs+radiation+intratumoral injection of 5-fluorouracil and chemoimmunotherapy+intratumoral injection of blemycin) were compared with the standard procedure (chemotherapy+radiation) for treating inoperable cancer in the cardioesophageal region. The study group included 47 patients aged 32-79. Tumors were inoperable due to considerable expansion in 32 and remote metastases in 15 patients. The single dose of 5-flyorouracil injected into tumor via a fibroendoscope at the start of chemoradiation treatment ranged 750-1000 mg (course dose of the drug - 2.75-4.25 g, total focal dose of radiation - 24-36 Gy). The single intratumoral dose of bleomycin injected prior to total polychemotherapy (vinblastin, ftorafur, cyclophosphamide) was 10-15 mg. In the control group receiving standard combined therapy, the total focal dose was 60-62 Gy and course dose of 5-fluorouracil - 5-7 g. Objective improvement was observed in 63.6% matched by a mean survival time of 14.6 months after combined therapy given in conjunction with supporting chemoimmunotherapy. This showed an improvement on the results of standard combination therapy which were 58.3% and 9.3 months, respectively

1985-01-01

257

Development of an in vivo radionuclide generator by labeling bleomycin with 191Os  

International Nuclear Information System (INIS)

Bleomycin (BLM) has been labeled with various radioisotopes and widely used in therapy and diagnosis. 191Os is a parent radionuclide with 15.4 day half-life and decays by beta emission to 191mIr, which is a radionuclide with 4.96 s half-life. BLM was labeled with 191Os-hexachloro-osmate and its distribution and stability in wild-type mice was determined. The complex was obtained at the pH 2 in normal saline at 90 deg C in 48 h. Radio-TLC showed an overall radiochemical yield of 93-97%, radio-chemical purity > 97%. The biodistribution study for 191Os-hexachloro-osmate and 191Os-BLM were carried in wild type-mice up to 14 days. Lungs, liver and spleen uptake increased 24-72 h after administration of 1910s-BLM. 24 h after administration, the radioactivity of the kidney increased and remained constant. (author)

2011-12-01

258

Mutagenicity of bleomycin and cross-adaptation with alkylating agents in Crepis capillaris  

Energy Technology Data Exchange (ETDEWEB)

The radiomimetic effect of bleomycin (BLM) at concentrations of 5 and 10 mg/l on root meristem cells was studied. The roots of germinating seeds of Crepis capillaris were exposed to BLM 16 h after the seeds were soaked. At this time, the root meristem cells were at the S or late G{sub 1} phase of the cell cycle. The mutagenic effect of BLM was found when the cells were fixed at the 29th, 32nd, 39th, 42nd, or 45th hour (i.e., the early germinating fraction). The aberrations induced included chromosome and chromatid rearrangements. At late fixations cells were observed which had, in addition to definite double-hit aberrations, multiple chromosomal breaks and pronounced chromosomal fragmentation. A hypothesis is advanced that BLM causes inducible repair that is similar to SOS-repair. This repair is prone to DNA synthesis errors, which account for the increase in the number of aberrations at late fixation times. Pretreatment with 1 {mu}g/ml of mitomycin C, an alkylating agent, before the exposure to 10 mg/l BLM, resulted in cross-adaptation, which drastically reduced the number of BLM-induced aberrations. This was especially evident for the number of aberrations and the number of cells affected at late fixations. 36 refs., 5 figs.

Dubinina, L.G. [Vavilov Institute of General Genetics, Moscow (Russian Federation)

1995-05-01

259

Cultured mouse SR-1 cells exposed to low dose of ?-rays become less susceptible to the induction of mutagenesis by radiation as well as bleomycin  

International Nuclear Information System (INIS)

The effect of pre-exposure of cultured mouse SR-1 cells to a low dose of ?-rays on the induction of mutations at the hprt locus by subsequent high dose radiation or bleomycin was studied. When cells were pre-exposed to 0.01 Gy ?-rays, the induction of mutations by a 3 Gy ?-ray dose given 18 or 24 h later was significantly reduced as compared with those which did not receive the low dose pre-exposure. When cells were challenged with 5 or 10 ?g/ml bleomycin for 12 h, which can produce double strand breaks in DNA, instead of 3 Gy ?-rays, a similar mutagenetic adaptive response was observed. The authors conclude that this resistance to radiation- or bleomycin-induced mutation is attributed to the induction of a DNA double-strand break repair mechanism. (Author)

1993-03-01

260

The combined effect of bleomycin and irradiation on mouse lip mucosa. 1. Influence of timing, sequence and mode of drug administration with single dose irradiation  

International Nuclear Information System (INIS)

The effect of the combination of single dose irradiation and bleomycin on the mucosa of the mouse lip was investigated. Bleomycin was administered either by IP injection or by subcutaneous continuous infusion. With the combined treatment an increased effect was observed compared to irradiation alone. The effect was drug-dose dependent in the range of doses used and was similar for both ways of drug administration. There was only a limited influence of timing and sequence of the two agents within a period of 4 days. Since the dose-response curves were shifted in a parallel way, a constant cell killing effect by bleomycin is suggested for all irradiation doses used. This could be due to independent cell kill by the drug, although some mechanism of interaction, such as interference with accumulation of sublethal radiation damage or a true dose modification can not be excluded. (Auth.)

1986-06-01

 
 
 
 
261

Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats  

International Nuclear Information System (INIS)

Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and inflammatory response during bleomycin-induced pulmonary fibrosis. Male Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3 times a week for 4 weeks) and/or thymoquinone (5 mg/kg/day, 1 week before and until the end of the experiment). Bleomycin significantly increased lung weight and the levels of Lactate dehydrogenase, total leucocytic count, total protein and mucin in bronchoalveolar lavage and these effects were significantly ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease in the antioxidant enzyme activity of superoxide dismutase and glutathione transferase. TQ treatment restored these markers toward normal values. TQ also counteracted emphysema in air alveoli, inflammatory cell infiltration, lymphoid hyperplastic cells activation surrounding the bronchioles and the over expression of activated form of nuclear factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was assessed by measuring hydroxyproline content, which increased markedly in the bleomycin group and significantly reduced by concurrent treatment with TQ. Furthermore, histopathological examination confirmed the antifibrotic effect of TQ. Collectively these findings indicate that TQ has potential antifibrotic effect beside its antioxidant activity that could be through NF-?B inhibition.

2012-12-16

262

Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats.  

Science.gov (United States)

Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and inflammatory response during bleomycin-induced pulmonary fibrosis. Male Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3 times a week for 4 weeks) and/or thymoquinone (5mg/kg/day, 1 week before and until the end of the experiment). Bleomycin significantly increased lung weight and the levels of Lactate dehydrogenase, total leucocytic count, total protein and mucin in bronchoalveolar lavage and these effects were significantly ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease in the antioxidant enzyme activity of superoxide dismutase and glutathione transferase. TQ treatment restored these markers toward normal values. TQ also counteracted emphysema in air alveoli, inflammatory cell infiltration, lymphoid hyperplastic cells activation surrounding the bronchioles and the over expression of activated form of nuclear factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was assessed by measuring hydroxyproline content, which increased markedly in the bleomycin group and significantly reduced by concurrent treatment with TQ. Furthermore, histopathological examination confirmed the antifibrotic effect of TQ. Collectively these findings indicate that TQ has potential antifibrotic effect beside its antioxidant activity that could be through NF-?B inhibition. PMID:22982510

El-Khouly, Dalia; El-Bakly, Wesam M; Awad, Azza S; El-Mesallamy, Hala O; El-Demerdash, Ebtehal

2012-12-16

263

Thymosin ?4 reduces IL-17-producing cells and IL-17 expression, and protects lungs from damage in bleomycin-treated mice.  

Science.gov (United States)

Thymosin ?4 (T?4) is a highly conserved peptide with immunomodulatory properties. In this research we investigated the effects of T?4 on the bleomycin-induced lung damage in CD-1 mice and the changes in the number of IL-17-producing cells as well as the IL-17 expression in the lung. Male CD-1 mice were treated with bleomycin (1mg/kg) in the absence or the presence of T?4 (6mg/kg delivered intra-peritoneally on the day of bleomycin treatment and for 2 additional doses). After sacrifice one week later, lung histology, measurement of collagen content of the lung, Broncho Alveolar Lavage Fluid (BALF) analysis, evaluation of IL17-producing cells in the blood as well as RT-PCR and IHC in the lung tissue were performed. As expected, bleomycin-induced inflammation and lung damage were substantially reduced by T?4 treatment in CD-1 mice, as shown by the significant reduction of (i) leukocytes in BALF, (ii) histological evidence of the lung damage, and (iii) total collagen content in the lung. Importantly, the bleomycin-induced increase in the number of IL17-producing cells in the blood was significantly blocked by T?4. Accordingly, IHC and RT-PCR results demonstrated that T?4 substantially inhibited bleomycin-induced IL-17 over-expression in the lung tissue. This is the first report showing that a decreased amount of IL17-producing cells and inhibited IL-17 expression in the lung with T?4 treatment correlate with its anti-inflammatory and anti-fibrotic effects. PMID:24613476

Conte, Enrico; Iemmolo, Maria; Fagone, Evelina; Gili, Elisa; Fruciano, Mary; Genovese, Tiziana; Esposito, Emanuela; Cuzzocrea, Salvatore; Vancheri, Carlo

2014-06-01

264

Induced pluripotent stem cells mediate the release of interferon gamma-induced protein 10 and alleviate bleomycin-induced lung inflammation and fibrosis.  

Science.gov (United States)

Chronic lung diseases cause serious morbidity and mortality, and effective treatments are limited. Induced pluripotent stem cells (iPSCs) lacking the reprogramming factor c-Myc (3-gene iPSCs) can be used as ideal tools for cell-based therapy because of their low level of tumorigenicity. In this study, we investigated whether 3-gene iPSC transplantation could rescue bleomycin-induced pulmonary fibrosis. After the induction of pulmonary inflammation and fibrosis via intratracheal delivery of bleomycin sulfate, mice were i.v. injected with 3-gene iPSCs or conditioned medium (iPSC-CM) at 24 h after bleomycin treatment. Administration of either 3-gene iPSCs or iPSC-CM significantly attenuated collagen content and myeloperoxidase activity, diminished neutrophil accumulation, and rescued pulmonary function and recipient survival after bleomycin treatment. Notably, both treatments reduced the levels of inflammatory cytokines and chemokines, including interleukin 1 (IL-1), IL-2, IL-10, tumor necrosis factor-?, and monocyte chemotactic protein 1 yet increased the production of the antifibrotic chemokine interferon-?-induced protein 10 (IP-10) in bleomycin-injured lungs. Furthermore, IP-10 neutralization via treatment with IP-10-neutralizing antibodies ameliorated the reparative effect of either 3-gene iPSCs or iPSC-CM on collagen content, neutrophil and monocyte accumulation, pulmonary fibrosis, and recipient survival. Intravenous delivery of 3-gene iPSCs/iPSC-CM alleviated the severity of histopathologic and physiologic impairment in bleomycin-induced lung fibrosis. The protective mechanism was partially mediated by the early moderation of inflammation, reduced levels of cytokines and chemokines that mediate inflammation and fibrosis, and an increased production of antifibrotic IP-10 in the injured lungs. PMID:23364435

How, Chorng-Kuang; Chien, Yueh; Yang, Kuang-Yao; Shih, Hsin-Chin; Juan, Chi-Chang; Yang, Yi-Ping; Chiou, Guang-Yuh; Huang, Pin-I; Chang, Yuh-Lih; Chen, Liang-Kung; Wang, Chien-Ying; Hsu, Han-Shui; Chiou, Shih-Hwa; Lee, Chen-Hsen

2013-03-01

265

National Sample Assessment Protocols  

Science.gov (United States)

These protocols represent a working guide for planning and implementing national sample assessments in connection with the national Key Performance Measures (KPMs). The protocols are intended for agencies involved in planning or conducting national sample assessments and personnel responsible for administering associated tenders or contracts,…

Ministerial Council on Education, Employment, Training and Youth Affairs (NJ1), 2012

2012-01-01

266

Transport Protocol Throughput Fairness  

Directory of Open Access Journals (Sweden)

Full Text Available Interest continues to grow in alternative transport protocols to the Transmission Control Protocol (TCP. These alternatives include protocols designed to give greater efficiency in high-speed, high-delay environments (so-called high-speed TCP variants, and protocols that provide congestion control without reliability. For the former category, along with the deployed base of ‘vanilla’ TCP – TCP NewReno – the TCP variants BIC and CUBIC are widely used within Linux: for the latter category, the Datagram Congestion Control Protocol (DCCP is currently on the IETF Standards Track. It is clear that future traffic patterns will consist of a mix of flows from these protocols (and others. So, it is important for users and network operators to be aware of the impact that these protocols may have on users. We show the measurement of fairness in throughput performance of DCCP Congestion Control ID 2 (CCID2 relative to TCP NewReno, and variants Binary Increase Congestion control (BIC, CUBIC and Compound, all in “out-of-the box” configurations. We use a testbed and endto- end measurements to assess overall throughput, and also to assess fairness – how well these protocols might respond to each other when operating over the same end-to-end network path. We find that, in our testbed, DCCP CCID2 shows good fairness with NewReno, while BIC, CUBIC and Compound show unfairness above round-trip times of 25ms.

Martin Bateman

2009-11-01

267

Comparative study of fixation of Co57 labelled bleomycin, labelled gallium citrate and Hg197 labelled mercury chloride, benign or malignant pulmonary lesions  

International Nuclear Information System (INIS)

Over the last ten years, numerous labelled molecules have been used in lung diseases, in order to attempt definite localisation of primary or secondary carcinoma. Three of these substances are now used: cobalt 57-labelled bleomycin, Hg197Cl2 and Ga67 citrate. A study of 34 patient with malignant or tuberculous lung disease with definite diagnosis, permitted demonstration of the fact that the highest uptake, or the best images, were obtained with labelled bleomycin. However, the long period of Co57 limits its indications in young subjects and, in these cases, HgCl2 is indicated

1975-01-01

268

Coded Splitting Tree Protocols  

DEFF Research Database (Denmark)

This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main design problem is determining the order of splitting, which enables successful decoding as early as possible. Evaluations show that the proposed protocol provides considerable gains over the standard tree splitting protocol applying SIC. The improvement comes at the expense of an increased feedback and receiver complexity.

Sørensen, Jesper Hemming; Stefanovic, Cedomir

2013-01-01

269

The effects of combined radiation and bleomycin therapy on the cervical lymph nodes metastasized with oral cancer  

International Nuclear Information System (INIS)

Effects of the concomitantly combined therapy of radiation and Bleomycin (60Co : 22.5 Gy and Bleomycin : 110 mg, i.m.) on the metastatic lymph nodes of cervical region in carcinoma of the oral cavity were examined histologically. The specimens studied were 44 metastatic lymph nodes obtained from 19 patients. Thirty six of the 44 metastatic lymph nodes were within irradiated field and they could be classified by Shimosato's grading system into 5 as Grade IV (no tumor cells remain), 11 as Grade III (non viable tumor cells only remain), 8 as Grade IIb (viable cells are few in number), 6 as Grade IIa (destruction of tumor structure is mild) and 6 as Grade I, 0 (no effects). Marked effects were noted in 16 lymph nodes (44.4 %) out of 36 irradiated metastatic lymph nodes, but there were no observable effects on the 8 lymph nodes which had not been included in the irradiated field. Marked effects were selectively in the superior internal jugular nodes, while the effect on the submandibular nodes was poor. Although the therapeutic potentiality was not affected by the size of the lymph nodes, histological features of the large metastatic nodes were not uniform but various in degenerative changes of the tumor cells within the same metastatic focus. The effectiveness of this combined therapy on the primary lesion and the metastatic foci, as evaluated by the histological examination, was almost parallel. Radiation dose of the present combination therapy in 50 % tumor disappearance rate was 7.7 Gy less than that of the radiation only. Accordingly, it was considered that the effect of one course of this combination therapy with 60Co 22.5 Gy and Bleomycin 110 mg on the metastatic lymph nodes corresponded to 60Co 30 Gy of single irradiation. (author)

1986-01-01

270

Distinct Roles of Ape1 Protein in the Repair of DNA Damage Induced by Ionizing Radiation or Bleomycin*  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Ionizing radiation (IR) and bleomycin (BLM) are used to treat various types of cancers. Both agents generate cytotoxic double strand breaks (DSB) and abasic (apurinic/apyrimidinic (AP)) sites in DNA. The human AP endonuclease Ape1 acts on abasic or 3?-blocking DNA lesions such as those generated by IR or BLM. We examined the effect of siRNA-mediated Ape1 suppression on DNA repair and cellular resistance to IR or BLM in human B-lymphoblastoid TK6 cells and HCT116 colon tumor cells. Partial A...

Fung, Hua; Demple, Bruce

2011-01-01

271

Bleomycin-resistance gene derived from the transposon Tn5 confers selective advantage to Escherichia coli K-12.  

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The plasmid pRAB2 contains a silent operon derived from the transposon Tn5 and carrying the gene neo for neomycin-kanamycin resistance and a truncated ble gene (ble333) for bleomycin resistance. Spontaneous mutants that express the two resistances provide Escherichia coli cells an improved fitness during the phase of decline in the absence of the antibiotics. It is shown that the ble333 gene product is responsible for this better fitness. These results can explain a previously described selec...

1991-01-01

272

Comprehensive microRNA analysis in bleomycin-induced pulmonary fibrosis identifies multiple sites of molecular regulation  

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The molecular mechanisms of lung injury and fibrosis are incompletely understood. MicroRNAs (miRNAs) are crucial biological regulators that act by suppressing their target genes and are involved in a variety of pathophysiological processes. To gain insight into miRNAs in the regulation of lung fibrosis, total RNA was isolated from mouse lungs harvested at different days after bleomycin treatment, and miRNA array with 1,810 miRNA probes was performed thereafter. MiRNAs expressed in lungs with ...

Xie, Ting; Liang, Jiurong; Guo, Rishu; Liu, Ningshan; Noble, Paul W.; Jiang, Dianhua

2011-01-01

273

Potentiation of mitomycin C, 6-mercaptopurine, bleomycin, cis-diamminedichloroplatinum and 5-fluorouracil by mycotrienins and mycotrienols.  

Science.gov (United States)

Mycotrienins I and II and mycotrienols I and II are ansamycin antibiotics containing a triene structure, isolated from Streptomyces rishiriensis. An amphotericin B-resistant clone (AMBR-1) derived from cultured Chinese hamster V79 cells was cross-resistant to mycotrienins I and II, but not to mycotrienol I or II. These four ansamycin antibiotics were found to potentiate significantly the action of some anti-cancer agents including 5-fluorouracil, cis-diamminedichloroplatinum, bleomycin, mitomycin C and 6-mercaptopurine against cultured V79 cells. The action of adriamycin was not potentiated. These four ansamycin antibiotics showed a synergism spectrum similar to that of smaller polyene antibiotics. PMID:6196249

Kuwano, M; Ikezaki, K; Mamizuka, K; Komiyama, S; Seto, H; Otake, N; Sugita, M; Yamaguchi, T; Kishiye, T; Fukawa, H

1983-10-01

274

Tissue uptakes of 67Ga-bleomycin and carrier free 67Ga in fibrosarcoma-bearing mice  

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67Gallium-bleomycin complex (67Ga-BLM) was prepared using Thakour method. Radio-thin-layer-chromatography of prepared complex showed A2 and B2 radiopeaks with Rf at 0.7 and 0.4 respectively with a purity of above % 95. Tissue uptake of 67Ga-BLM and 67GaCl3 in twelve tissues including tumor, blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content ,bladder and the total body were counted by well counter at 1, 2, 4, 24 and 48 hours post injection of radiopharmaceuticals. Up...

2004-01-01

275

Bleomycin sulfate-induced micronuclei in human, rat, and mouse peripheral blood lymphocytes.  

Science.gov (United States)

The sensitivity to micronucleus (MN) induction of human, mouse, and rat peripheral blood lymphocytes (PBLs) exposed to bleomycin sulfate (BLM) in vitro was compared in cytochalasin B-induced binucleated (BN) cells. For the PBLs of each species, either 0, 5, 10, 20, 40, 60, 80, or 160 micrograms/ml BLM was added to 5 ml aliquots of whole blood for 4 hr at 37 degrees C in a 5% CO2 atmosphere. Leukocytes were isolated on a density gradient and cultured in the presence of phytohemagglutinin to stimulate blastogenesis, and cytochalasin B was added to each culture at 21 hr postinitiation to prevent cytokinesis. A total of 4,000 BNs/concentration/species was analyzed for MN in two independent experiments. In addition, multiple-MN-BNs were quantitated, and the nucleation index was determined. Significant increases both in total MN-BNs and multiple-MN-BNs were observed at all concentrations in all species. All three species' concentration-response curves gave good fits (r2 values from 0.87 to 0.95) to either a linear or a square root model (y = mx + b or y = m[x]0.5 + b, respectively; where y = the percentage of MN-BN, m is the slope, and b is the y-intercept). The MN induction in the human and rat PBLs was not statistically different, but both were significantly less sensitive than the response shown by the BLM-exposed mouse PBLs. This difference in MN susceptibility was observed only at BLM test concentrations > or = 20 micrograms/ml. The nucleation index was significantly decreased in all species at either 80 or 160 micrograms/ml. PMID:7533077

Erexson, G L; Bryant, M F; Kwanyuen, P; Kligerman, A D

1995-01-01

276

Nucleosome rearrangement in human cells following short patch repair of DNA damaged by bleomycin  

Energy Technology Data Exchange (ETDEWEB)

We have examined the structure of newly repaired regions of chromatin in intact and permeabilized human cells following exposure to bleomycin (BLM). The average repair patch size (in permeabilized cells) was six to nine bases, following doses of 1-25 micrograms/mL BLM, and greater than 80% of the total repair synthesis was resistant to aphidicolin. In both intact and permeabilized cells, nascent repair patches were initially very sensitive to staphylococcal nuclease, analogous to repair induced by long patch agents, and are nearly absent from isolated nucleosome core DNA. Unlike long patch repair, however, the loss of nuclease sensitivity during subsequent chase periods was very slow in intact cells, or in permeabilized cells treated with a low dose of BLM (1 microgram/mL), and was abolished by treatment with hydroxyurea (HU) or aphidicolin (APC). The rate of repair patch ligation did not correlate with this slow rate of chromatin rearrangement since greater than 95% of the patches were ligated within 6 h after incorporation (even in the presence of HU or APC). In permeabilized cells, repair patches induced by either 5 or 25 micrograms/mL BLM, where significant levels of strand breaks occur in compact regions of chromatin, lost the enhanced nuclease sensitivity at a rate similar to that observed following long patch repair. This rapid rate of rearrangement was not affected by APC. These results indicate that short patch repair in linker regions of nucleosomes, and/or open regions of chromatin, involves much less nucleosome rearrangement than long patch repair or short patch repair in condensed chromatin domains.

Sidik, K.; Smerdon, M.J. (Washington State Univ., Pullman (USA))

1990-08-14

277

Bleomycin sulphate loaded nanostructured lipid particles augment oral bioavailability, cytotoxicity and apoptosis in cervical cancer cells.  

Science.gov (United States)

In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4±5.4nm and 45.3±3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH?6.8±0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (?5.6 fold lower IC50), improved intracellular concentration (?4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (PBLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (PBLM solution (19.56±0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings. PMID:24732397

Saini, Jyoti; Bansal, Vikas; Chandra, Ankush; Madan, Jitender; Jain, Upendra Kumar; Chandra, Ramesh; Jain, Sarvesh Malviya

2014-06-01

278

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats  

Directory of Open Access Journals (Sweden)

Full Text Available Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1 intratracheal (IT phosphate-buffered saline (PBS + intraperitoneal (IP PBS (n=7; (2 IT BLM + IP PBS (n=8; (3 IT BLM + low dose (LD simvastatin (1 mg/kg daily, n=8; (4 IT BLM + high dose (HD simvastatin (5 mg/kg daily, n=8. Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-?, TGF-p1 levels in bronchoalveolar lavage (BAL fluid and lung tissue hydroxyproline (HPL content and by histopathological examination (Ashcroft score. BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all. While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05 and TGF-?1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05. Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.

Baykal Tulek

2012-01-01

279

Ultrastructural changes of human esophageal carcinoma induced by preoperative treatments with bleomycin and/or radiation  

International Nuclear Information System (INIS)

In the present study, 44 cases of esophageal carcinoma were electron-microscopically examined. Nuclear bodies of various types observed in carcinoma cells or in normal mucosa of the esophagus treated by bleomycin and radiation, single or combined (BLM/R), were classified into seven types. Types A and B were observed in carcinoma cells of both conditions of untreated or treated with BLM/R. Types C, D and E were specific findings in squamous carcinoma cells after BLM/R treatment. Types F and G were considered to be far advanced in terms of other nuclear bodies and were observed in strongly affected carcinoma cells. These nucleolar changes were considered to be specific alterations induced by BLM in esophageal carcinoma cells. The appearance of various nuclear bodies and a series of nucleolar segregation after BLM/R treatments were confirmed as well in metastatic lesions of abdominal lymph nodes that may be affected only with minimal or disregardable scattered radiation, if any, giving no sifnificant influence to cell activity. This fact has suggested that types C, D and E nuclear bodies and nucleolar segregation are changes specific to BLM/R treatments, some solely to BLM. Other nuclear changes consisted in the appearance of fibrillar structures of three different types that were considered to have been produced by disturbed ribosomal activity in the nuclei. On the basis of results in the present study, BLM apparently showed serious evidence of remarkable influences or effects, although not constantly and generally available, on certain squamous carcinoma cells of the esophagus. Some of the evidence was represented by nucleolar segregation and characteristic nuclear bodies of different types, particularly of types C, D and E. (J.P.N.)

1982-01-01

280

Effect of time intervals between bleomycin and irradiation on cell lethality  

International Nuclear Information System (INIS)

Experiments have been carried out to determine the effect on the cell survivals of different time intervals between bleomycin (BLM) and irradiation in either in vivo or in vitro system. When BLM (100 mg/kg) was given between 24 and 0 hours before a dose of 13.5 Gy, an enhancement by BLM of the response of the intestinal epithelial cells to irradiation was found. Especially, when BLM was given 2 hours before irradiation, the maximum enhancement was observed with the dose modifying factor of 1.4. When 8 mm FSa tumor in the right thighs were treated by combination of BLM (50 mg/kg) and irradiation (20 Gy), the different time intervals between the two agents did not modify tumor growth. The same results were observed with 4-days old lung micrometastases. V79 cells both in the exponentially growing phase and is the plateau phase (more than 80 % of cells were in G1-like stage in the cell cycle) were treated with BLM with/without irradiation. The cells in the plateau phase were more sensitive to the drug than those in the proliferative phase. When BLM (30 ug/ml) was combined with irradiation (7.5 Gy) at the different time intervals, a significant enhancement of the response by BLM was found in the cells in the plateau phase, and BLM, given 1 hour before irradiation, gave the least survival rate with the dose-modifying factor of 1.4. These results suggest that the plateau phase cells show the very similar response as the intestinal epithelial cells, when they were treated by BLM combined with irradiation. We think that the plateau phase cells are suitable to expect the in vivo damage of the normal tissue from in vitro experiments. (author)

1987-01-01

 
 
 
 
281

Preventive and therapeutic effects of physical exercise on bleomycin-induced lung injury and oxidative stress  

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Full Text Available Studies have shown that regular physical exercise of moderate intensity is an important tool for the control of pulmonary oxidative stress. The objective of this study was to examine the preventive and therapeutic effect of physical exercise on oxidative stress in the lungs of mice exposed to bleomycin (BLM. Thirty-six male mice (CF1, 30-35 g received a single endotracheal dose of BLM (2.5 U/kg body weight dissolved in 0.25 mL 0.9% NaCl or saline (0.9% NaCl and were divided into six groups (n=6: untrained saline or BLM, preventive training saline or BLM, and therapeutic training saline or BLM. The trained groups underwent a program of progressive exercise on a treadmill for 8 weeks (up to 17 m.min-1, 50 min.day-1. The preventive group started the exercise program 62 days before the administration of BLM and the therapeutic group 62 days after the administration of BLM. All animals were killed by decapitation 48 hours after the experimental period, and the right lung was surgically removed for the determination of biochemical parameters. Hydroxyproline content, TBARS level, protein carbonylation, and superoxide dismutase (SOD and catalase (CAT activities were analyzed. The results showed that preventive and therapeutic training led to a significant reduction in hydroxyproline content and inhibited the increase in oxidative damage to lipids and proteins. However, only therapeutic training decreased SOD and CAT activities in mice exposed to BLM. The results suggest that preventive and therapeutic physical exercise is able to minimize pulmonary oxidative stress induced by BLM.

Ricardo Aurino Pinho

2009-09-01

282

Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis  

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Full Text Available Abstract Background The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1 is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases. Results Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e.g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i the degree of inflammation at day 7; and ii indexes of fibrosis (assessed by deposition of hydroxyproline in the lung at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF-?1, IFN-? and TNF-? generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21 or therapeutically (from day 14 onward, ameliorated both signs of inflammation and fibrosis. Conclusion Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis.

Flower Roderick J

2011-10-01

283

Effects of combined treatment with radiation and bleomycin on the primary oral carcinoma  

Energy Technology Data Exchange (ETDEWEB)

Eighty-two previously untreated patients with squamous cell carcinoma arising from the oral mucosa were treated by concurrent combined treatment with 22.5 Gy of radiation and 110 mg of bleomycin or 55 mg of peplomycin at our department from 1976 to 1985. Therapeutic effects were examined clinically and histologically, and the role as a preoperative treatment was discussed. Moreover, a statistical analysis was performed to determine the factors related to the histological effects. 1. The ratio of complete response was 42.7 % and the ratio of partial response was 89.0 %. 2. 59 patients had subsequent treatment with surgery. Step sections were prepared from surgically resected specimens and examined microscopically. 1) According to Shimosato's classification of histological effects, 19 belonged to Grade III/IV, 15 to IIb, 13 to IIa and 12 to I/0. 2) In 7 of 15 Grade IIb patients, residual survival cancer cells were not observed at the margin of the area previously occupied by tumor at the beginning of treatment. Accordingly, 44.1 % (7 with IIb and 19 with III/IV) of 59 patients may be controlled by the more conservative surgery. 3. 18 patients with CR received additional combined therapy alone without any further treatment. Local control rate of these patients was 66.7 %. Therefore, 31 patients (these 12 patients and 19 of Grade III/IV) could be controlled by this therapy alone. 4. The histological effects significantly depended on the following factors of tumors; size, growth pattern, and degree of histologic differentiation. 82.2 % of 73 patients could be classified into good effective group or poor group accurately by the quantification theory Type II of Hayashi. It is considered that this method is useful for predicting the effects of this combined treatment. (author) 57 refs.

Okamoto, Manabu

1988-07-01

284

Histopathologic observation of anti-tumor effect of bleomycin and irradiation on cancers of tongue  

Energy Technology Data Exchange (ETDEWEB)

Nine cases of squamous cell carcinoma of the tongue were treated by either intramuscular or local injections of total 60 to 200 mg of Bleomycin (BLM), and 7 cases by total doses of 1,200 to 5,320 rads of irradiation, followed by surgical removal of primary neoplasm. The histologic examination was done focussing on the antitumor effect of both treatments. In the cases with keratinizing component more than 25 % in the biopsy specimens, the earliest change due to BLM was vacuolar degeneration of proliferating cells either at the base of superficial cancer epithelia or at the periphery of invading cancer foci. When the proliferating cancer cells disappeared, an appearance of invading cancer foci resembled that of ectopic islands of normal squamous epithelium. These foci of differentiated squamous cell carcinoma gradually underwent morphological change into the so-called cancer pearls. Finally, the cancer pearls degenerated, leaving foreign bodies consisting of concreted keratin. The stromal reaction was characterized by the formation of granulation tissues accompanying significant numbers of foreign body giant cells. In the cases of lingual carcinoma with poor squamous differentiation, these processes were indistinct. Instead, the proliferating anaplastic cancer cells were markedly reduced and the remaining cancer cells transformed into large bizarre cells, probably at degenerative stage. On the histologic level, irradiation showed essentially similar antitumor effect to BLM, except for the rapid formation of concreted keratin bodies accompanying more abundant foreign body giant cells and the presence of irregular granulation tissues at different stages. We concluded that both BLM and irradiation had a powerful antitumor action on squamous cell carcinoma of the tongue.

Kohmura, Yuji (Aichi-Gakuin Univ., Nagoya (Japan). School of Dentistry); Hosoda, Syun; Kawabe, Yoshitaka; Isojima, Genzo

1983-05-01

285

Bleomycin hydrolase and hyperhomocysteinemia modulate the expression of mouse proteins involved in liver homeostasis.  

Science.gov (United States)

The liver is the major contributor to homocysteine (Hcy) metabolism and fatty liver disease is associated with hyperhomocysteinemia. Bleomycin hydrolase (Blmh) is an aminohydrolase that also participates in Hcy metabolism by hydrolyzing Hcy-thiolactone. To gain insight into hepatic functions of Blmh, we analyzed the liver proteome of Blmh(-/-) and Blmh(+/+) mice in the absence and presence of diet-induced (high methionine) hyperhomocysteinemia using 2D IEF/SDS-PAGE gel electrophoresis and MALDI-TOF mass spectrometry. We identified eleven liver proteins whose expression was significantly altered as a result of the Blmh gene inactivation. The differential expression (Blmh(-/-) vs. Blmh(+/+)) of four liver proteins was lower, of two proteins was higher, and was further modified in mice fed with a hyperhomocysteinemic high-Met diet. The down-regulated proteins are involved in lipoprotein metabolism (ApoA1, ApoE), antigen processing (Psme1), energy metabolism (Atp5h, Gamt), methylglyoxal detoxification (Glo1), oxidative stress response (Sod1), and inactivation of catecholamine neurotransmitters (Comt). The two up-regulated proteins are involved in nitric oxide generation (Ddah1) and xenobiotic detoxification (Sult1c1). We also found that livers of Blmh(-/-) mice expressed a novel variant of glyoxalase domain-containing protein 4 (Glod4) by a post-transcriptional mechanism. Our findings suggest that Blmh interacts with diverse cellular processes-from lipoprotein metabolism, nitric oxide regulation, antigen processing, and energy metabolism to detoxification and antioxidant defenses-that are essential for liver homeostasis and that modulation of these interactions by hyperhomocysteinemia underlies the involvement of Hcy in fatty liver disease. PMID:24633403

Suszy?ska-Zajczyk, Joanna; Wróblewski, Jacek; Utyro, Olga; Luczak, Magdalena; Marczak, Lukasz; Jakubowski, Hieronim

2014-06-01

286

Bleomycin effect on L5178Y cells; Dzialanie bleomycyny na komorki podlinii L5178Y  

Energy Technology Data Exchange (ETDEWEB)

We analyzed the effects of treatment with bleomycin (BLM) in 2 sublines of L5178Y (LY) murine lymphoma, LY-R, radioresistant, and LY-S, radiosensitive. LY-S cells were 2 times more sensitive to BLM than LY-R cells, similarly as in the case of X rays. Since there was no difference in the activity of drug transport system, this different susceptibility to BLM probably was due to the DNA repair defect in LY-S cells. Growth was impaired proportionally to the lethal effect and continued (days 3-6 after treatment with 50 microM BLM) until the elimination of dead cells from the cell population; 24 h after treatment cell cycle distributions indicated the presence of block in S phase (proportional to the dose of BLM). Contrarily to X or gamma-irradiation, BLM did not induce any block in the G2 phase. Initial DNA damage, estimated by the single cell gel electrophoresis, was linearly related to the dose of BLM in LY-S cells; in LY-R cells the damage level was significantly higher than in LY-S cells. In the higher (>10 microM BLM) dose range both dose - effect curves became identical. In gamma-irradiated LY-R and LY-S cells the dose - effect curves were identical. DNA damage distribution in BLM treated LY cells was much less uniform than in the gamma-irradiated ones; it indicated the presence of heavily damaged cells, a feature typical for BLM action. (author). 29 refs, 28 figs.

Zaim, J.; Kruszewski, M.; Gradzka, I. [Institute of Nuclear Chemistry and Technology, Warsaw (Poland)

1997-08-01

287

Protective and therapeutic effect of molsidomine on bleomycin-induced lung fibrosis in rats.  

Science.gov (United States)

We aimed to investigate the preventive and treatment effect of molsidomine (MOL) on bleomycin (BLC)-induced lung injury in rats. Rats were assigned into groups as follows: control group; MOL group, 10 mg/kg MOL was continued orally for 29 day; BLC group, a single intratracheal injection of BLC (2.5 mg/kg), MOL+BLC-preventive group, 10 mg/kg MOL was administered 1 day before the intratracheal BLC injection and continued for 14 days; BLC+MOL-treatment group 10 mg/kg MOL was given on 14th day after the intratracheal BLC injection and continued until sacrifice. All animals were sacrificed on 29th day after BLC administration. The semiquantitative histopathological assessment, tissue levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), myeloperoxidase (MPO), and oxidative stress index (OSI) were measured. BLC-provoked histological changes were significantly detected compared to the control group. MOL restored these histological damages in different quantity in the treatment and preventive groups. BLC administration significantly decreased levels of GSH and TAS when compared to controls and these reductions was significantly ameliorated by MOL given prophylactic setting. However, therapeutic MOL administration significantly increased the TAS level decreased by BLC. The levels of MDA, MPO, and TOS were significantly increased with BLM, and these augmentations of MDA and TOS were significantly reduced by MOL given prophylactic setting. Furthermore, the OSI was higher in the BLC group, and this increase was reversed by the MOL administration before and after BLC treatment. In this study, both protective and therapeutic effects of MOL against BLC-induced lung fibrosis were demonstrated for the first time. PMID:24526289

Kilic, Talat; Parlakpinar, Hakan; Polat, Alaadin; Taslidere, Elif; Vardi, Nigar; Sarihan, Ediz; Ermis, Hilal; Tanbag, Kevser

2014-08-01

288

CTEP & CC Protocols - Credit Report  

Science.gov (United States)

CTEP & CC Protocols - Credit Report Community Clinical Oncology Program Research Base Protocol Credit Assignment Approved, Active, and Closed Protocols Research Base Cancer and Leukemia Group B (CALGB) qry_Credit_Report_Output_HTML_CALGB

289

The Singapore protocol  

International Nuclear Information System (INIS)

Full text: We present a new qubit protocol for quantum key distribution which exploits the potential of minimal state tomography and proves to be more efficient than other tomographic protocols. Under ideal circumstances the efficiency is 0.415 key-bits per qubit sent 25 % higher than the efficiency of 0.333 for the standard 6-state protocol of BB84 type. We describe a simple two-way communication scheme that extracts 0.4 key bits per qubit and thus gets close to the information theoretical limit and report noise thresholds for secure key bit generation in the presence of unbiased noise under various eavesdropping attacks. (author)

2005-05-20

290

Timed Analysis of Security Protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

We propose a method for engineering security protocols that are aware of timing aspects. We study a simplified version of the well-known Needham Schroeder protocol and the complete Yahalom protocol, where timing information allows the study of different attack scenarios. We model check the protocols using UPPAAL. Further, a taxonomy is obtained by studying and categorising protocols from the well known Clark Jacob library and the Security Protocol Open Repository (SPORE) lib...

Corin, R.; Etalle, S.; Hartel, P. H.; Mader, A.

2005-01-01

291

Timed Analysis of Security Protocols  

CERN Document Server

We propose a method for engineering security protocols that are aware of timing aspects. We study a simplified version of the well-known Needham Schroeder protocol and the complete Yahalom protocol, where timing information allows the study of different attack scenarios. We model check the protocols using UPPAAL. Further, a taxonomy is obtained by studying and categorising protocols from the well known Clark Jacob library and the Security Protocol Open Repository (SPORE) library. Finally, we present some new challenges and threats that arise when considering time in the analysis, by providing a novel protocol that uses time challenges and exposing a timing attack over an implementation of an existing security protocol.

Corin, R; Hartel, P H; Mader, A

2005-01-01

292

Neck Injury Assessment Protocol.  

Science.gov (United States)

The report is a protocol of suggested autopsy procedures based upon an autopsy examination and study of twenty-two motor vehicular deaths, studied at the Department of Chief Medical Examiner-Coroner, County of Los Angeles, California.

G. Hieshima H. H. Itabashi I. Rehman T. T. Noguchi V. S. Grinnell

1978-01-01

293

Asset Maintenance Protocol  

The Environment Agency's approach to maintaining flood and coastal risk management assets in England. The Asset Maintenance Protocol describes how we decide which assets we maintain and how we work with those affected by our decisions.

294

Quantum deniable authentication protocol  

Science.gov (United States)

The proposed quantum identity authentication schemes only involved authentication between two communicators, but communications with deniability capability are often desired in electronic applications such as online negotiation and electronic voting. In this paper, we proposed a quantum deniable authentication protocol. According to the property of unitary transformation and quantum one-way function, this protocol can provide that only the specified receiver can identify the true source of a given message and the specified receiver cannot prove the source of the message to a third party by a transcript simulation algorithm. Moreover, the quantum key distribution and quantum encryption algorithm guarantee the unconditional security of this scheme. Security analysis results show that this protocol satisfies the basic security requirements of deniable authentication protocol such as completeness and deniability and can withstand the forgery attack, impersonation attack, inter-resend attack.

Shi, Wei-Min; Zhou, Yi-Hua; Yang, Yu-Guang

2014-07-01

295

Verifying authentication protocol implementations  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Formal methods for verifying authentication protocols tend to assume an idealised, perfect form of encryption. This approach has been spectacularly successful in finding flaws, but when we aim for proofs of correctness then we need to consider this assumption more carefully, and perhaps to weaken it to reflect properties of real cryptographic mechanisms. This paper reviews the existing CSP approach to verifying protocols, and considers how algebraic properties of real cryptographic mecha...

Schneider, Steve A.

2002-01-01

296

The Effect of Bleomycin to the Satellite Association who were Exposed to Radiation (X-Ray Chronically  

Directory of Open Access Journals (Sweden)

Full Text Available Beginning with the therapeutic dose and increasing three differentdoses and three different periods of time Bleomycin (Bleomycin 0.3 ?g/ml, 3?g/ml and 30 ?g/ml, 6,24, 48 hours were added to blood which was beingcultured on 5 samples who were exposed to radiation (x-ray chronically.The satellite association was evaluated in 2639 metaphases frompreparations belong to control and experiment groups.The satellite association was showed difference value to the differencebleomycin dose and the between difference samples. As the satelliteassociation 31.7% for the control group, this value fall to 30.9% at 0.3?g/ml, 27.2% at 3 ?g/ml and 19.7% at 30 ?g/ml. Statistically; there were nosignificant differences between in the 6 hour control group and dose groups(P>0.05. There were significant differences between in the 24 hour controlgroup and 30 ?g/ml dose groups (P<0.05. There were significantdifferences between in the 48 hour control group and 3 ?g/ml and 30 ?g/mldose groups (P<0.01.

Hilmi ?si

2004-01-01

297

The Sprague Dawley rats as biomodel in the induction of micronuclei in bone marrow cells by cyclophosphamide and bleomycin  

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Full Text Available The micronuclei assay in bone marrow is easily to reproduce and its offer clear information on the cellular proliferation in bone marrow. This system allow registering in vivo the capacity of the chemical substances to induce chromosomics ruptures to interfere or the chromosomes metaphases migration during the mitosis of the somatic cells. In this article wedecide to evaluate the Sprague Dawley rats in both sexes as biomodel in the induction of micronuclei in bone marrow cells by cyclophosphamide and bleomycin. Which were formed 5 experimental groups per sex, the first administered with NaCl 0,9 % by intraperitoneal (i.p route, the second and third groups were administered with cyclophosphamide by i.p route,with designs of different treatments at doses of 50 mg/kg. The fourth and fifth groups were administered with bleomycin by i.p route, equally in two designs of different treatments at doses of 40 mg/kg. At the end of the experience obtained higher results of the micronucleis inductions with the use of cyclophosphamide was administered 48 and 24 hours beforesacrifice in SD rats of both sexes. That which constitutes in our experimental conditions the best experimental design to induce the micronucleis formation in bone marrow cells of rodents, increasing considerably the spontaneous frequency to present in this species of rat, useful in evaluation studies on in vivo antigenotoxic drugs effects.

Daniel Francisco Arencibia Arrebola

2010-04-01

298

Genetic ablation of mast cells redefines the role of mast cells in skin wound healing and bleomycin-induced fibrosis.  

Science.gov (United States)

Conclusive evidence for the impact of mast cells (MCs) in skin repair is still lacking. Studies in mice examining the role of MC function in the physiology and pathology of skin regenerative processes have obtained contradictory results. To clarify the specific role of MCs in regenerative conditions, here we used a recently developed genetic mouse model that allows conditional MC ablation to examine MC-specific functions in skin. This mouse model is based on the cell type-specific expression of Cre recombinase in connective tissue-type MCs under control of the Mcpt5 promoter and the Cre-inducible diphtheria toxin receptor-mediated cell lineage ablation by diphtheria toxin. In response to excisional skin injury, genetic ablation of MCs did not affect the kinetics of reepithelialization, the formation of vascularized granulation tissue, or scar formation. Furthermore, genetic ablation of MCs failed to prevent the development of skin fibrosis upon bleomycin challenge. The amount of deposited collagen and the biochemistry of collagen fibril crosslinks within fibrotic lesions were comparable in MC-depleted and control mice. Collectively, our findings strongly suggest that significant reduction of MC numbers does not affect skin wound healing and bleomycin-induced fibrosis in mice, and provide to our knowledge previously unreported insight in the long-debated contribution of MCs in skin regenerative processes. PMID:24406680

Willenborg, Sebastian; Eckes, Beate; Brinckmann, Jürgen; Krieg, Thomas; Waisman, Ari; Hartmann, Karin; Roers, Axel; Eming, Sabine A

2014-07-01

299

Definition of the intermediates and mechanism of the anticancer drug bleomycin using nuclear resonance vibrational spectroscopy and related methods.  

Energy Technology Data Exchange (ETDEWEB)

Bleomycin (BLM) is a glycopeptide anticancer drug capable of effecting single- and double-strand DNA cleavage. The last detectable intermediate prior to DNA cleavage is a low spin Fe{sup III} peroxy level species, termed activated bleomycin (ABLM). DNA strand scission is initiated through the abstraction of the C-4{prime} hydrogen atom of the deoxyribose sugar unit. Nuclear resonance vibrational spectroscopy (NRVS) aided by extended X-ray absorption fine structure spectroscopy and density functional theory (DFT) calculations are applied to define the natures of Fe{sup III}BLM and ABLM as (BLM)Fe{sup III}-OH and (BLM)Fe{sup III}({eta}{sup 1}-OOH) species, respectively. The NRVS spectra of Fe{sup III}BLM and ABLM are strikingly different because in ABLM the {delta}Fe-O-O bending mode mixes with, and energetically splits, the doubly degenerate, intense O-Fe-N{sub ax} transaxial bends. DFT calculations of the reaction of ABLM with DNA, based on the species defined by the NRVS data, show that the direct H-atom abstraction by ABLM is thermodynamically favored over other proposed reaction pathways.

Liu, L. V.; Bell, C. B., III; Wong, S. D.; Wilson, S. A.; Kwak, Y.; Chow, M.S.; Zhao, J.; Hodgson, K.O.; Hedman, B.; Solomon, E.I. (X-Ray Science Division); (Stanford Univ.); (SLAC)

2010-12-28

300

Low-magnification image analysis of Giemsa stained, electroporation and bleomycin treated endothelial monolayers provides reliable monolayer integrity data.  

Science.gov (United States)

The aim of this study was to develop an in vitro cell model for studying the in vivo observed vascular effect, induced by exposing blood vessels to changing electric field strengths. Human microvascular endothelial cells (HMEC-1) were cultured as monolayers on 8 chamber glass slides as a model of capillary wall. Exposed to electric pulses alone, or in the presence of bleomycin (electrochemotherapy), monolayers were incubated with culture medium, fixed with methanol, stained with Giemsa, and photographed. Images of high-contrast low-magnification monolayers made under identical optimal light exposure were converted to greyscale, and the use of a threshold tool yielded a binary distribution, from which we determined two parameters of monolayer integrity: the covered surface area and the number of cells. We show that this low-magnification image analysis method for attached endothelial cells provides reliable control parameters of monolayer integrity, representing capillary wall. Besides, already within 2h post-treatment the data show distinct effects in the monolayer integrity parameters for electric pulses alone, or in the presence of bleomycin. The present method can be readily introduced to short and long-term toxicity assays with a variety of treatment conditions. PMID:24412537

Meulenberg, Cécil J W; Cemazar, Maja

2014-06-01

 
 
 
 
301

Interaction of the antiemetics ondansetron and granisetron with the cytotoxicity induced by irradiation, epirubicin, bleomycin, estramustine, and cisplatin in vitro  

Energy Technology Data Exchange (ETDEWEB)

At cancer treatment, the use of antiemetics are often needed due to induction of nausea and vomiting. Some antiemetics have been shown to interact with the direct cytotoxic effects. The newly developed antiemetics have, so far as we know, not been studied in this respect. In the present study, the effects of the 5-HT{sub 3} receptor antagonists ondansetron and granisetron were evaluated on the cytotoxicity, induced by irradiation, bleomycin, epirubicin, estramustine, and cisplatin using fibroblasts (V79) and lung cancer cells (P31) in vitro. Ondansetron or granisetron (10{sup -5} mol/l) had no effect on the survival of irradiated cells. Granisetron (10{sup -5} mol/l) significantly potentiated cytoxocity of 2.5 mg/l epirubicin on fibroblasts whereas the effect of granisetron (10{sup -7} mol/l) on the cytotoxic effect of 25 mg/l bleomycin, and estramustine (80 mg/l) seemed additive to lung cancer cells. Ondansetron was non-interactive with the cytotoxicity induced by any of the anti-cancer drugs. Although the encountered observation with an enhancing effect of granisetron on the epirubicin-induced cytotoxicity is seen in a specific experimental situation in vitro, the fact that 5-HT{sub 3} receptor antagonists are routinely used during cancer treatment indicate that attention should be given to a possible interaction with the antineoplastic action of cancer treatment. (orig.).

Behnam Motlagh, P. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Henriksson, R. [Dept. of Oncology, Umeaa Univ. Hospital (Sweden); Grankvist, K. [Dept. of Clinical Chemistry, Umeaa Univ. Hospital (Sweden)

1995-12-31

302

Atorvastatin Attenuates Bleomycin-Induced Pulmonary Fibrosis via Suppressing iNOS Expression and the CTGF (CCN2/ERK Signaling Pathway  

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Full Text Available Pulmonary fibrosis is a progressive and fatal lung disorder with high mortality rate. To date, despite the fact that extensive research trials are ongoing, pulmonary fibrosis continues to have a poor response to available medical therapy. Statins, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known for its broad pharmacological activities, remains a remedy against multiple diseases. The present study investigated the antifibrotic potential of atorvastatin against bleomycin-induced lung fibrosis and to further explore the possible underlying mechanisms. Our results showed that atorvastatin administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. Atorvastatin reduced malondialdehyde (MDA level and lung indices. Atorvastatin also markedly decreased the expression of inducible nitric oxide synthase (iNOS in lung tissues and, thus, prevented nitric oxide (NO release in response to bleomycin challenge. Furthermore, atorvastatin exhibited target down-regulation of connective tissue growth factor (CTGF (CCN2 and phosphorylation extracellular regulated protein kinases (p-ERK expression. Taken together, atorvastatin significantly ameliorated bleomycin-induced pulmonary fibrosis in rats, via the inhibition of iNOS expression and the CTGF (CCN2/ERK signaling pathway. The present study provides evidence that atorvastatin may be a potential therapeutic reagent for the treatment of lung fibrosis.

Bo Zhu

2013-12-01

303

Automated Composition of Security Protocols  

CERN Document Server

Determining if two protocols can be securely composed requires analyzing not only their additive properties but also their destructive properties. In this paper we propose a new composition method for constructing protocols based on existing ones found in the literature that can be fully automatized. The additive properties of the composed protocols are ensured by the composition of protocol preconditions and effects, denoting, respectively, the conditions that must hold for protocols to be executed and the conditions that hold after executing the protocols. The non-destructive property of the final composed protocol is verified by analyzing the independence of the involved protocols, a method proposed by the authors in their previous work. The fully automatized property is ensured by constructing a rich protocol model that contains explicit description of protocol preconditions, effects, generated terms and exchanged messages. The proposed method is validated by composing 17 protocol pairs and by verifying t...

Genge, Bela; Haller, Piroska

2009-01-01

304

Optimal Protocols for Nonlocality Distillation  

CERN Multimedia

Forster, Winkler, and Wolf recently showed that weak nonlocality can be amplified by giving the first protocol that distills a class of nonlocal boxes (NLBs) [Phys. Rev. Lett. 102, 120401 (2009)]. We first show that their protocol is optimal among all non-adaptive protocols. We next consider adaptive protocols. We show that the depth 2 protocol of Allcock et al. [Phys. Rev. A 80, 062107, (2009)] performs better than previously known adaptive depth 2 protocols for all symmetric NLBs. We present a new depth 3 protocol that extends the known region of distillable NLBs. We give examples of NLBs for which each of Forster et al.'s, Allcock et al.'s, and our protocol performs best. The new understanding we develop is that there is no single optimal protocol for NLB distillation. The choice of which protocol to use depends on the noise parameters for the NLB.

Hoyer, Peter

2010-01-01

305

Holistic analysis of mix protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Security protocols are often analysed in isolation as academic challenges. However, the real world can require various combinations of them, such as a certified email protocol executed over a resilient channel, or the key registration protocol to precede the purchase protocols of Secure Electronic Transactions (SET). We develop what appears to be the first scalable approach to specifying and analysing mix protocols. It expands on the Inductive Method by exploiting the simplicity with...

Bella, Giampaolo; Butin, Denis Fre?de?ric; Gray, David

2011-01-01

306

Blind Cognitive MAC Protocols  

CERN Document Server

We consider the design of cognitive Medium Access Control (MAC) protocols enabling an unlicensed (secondary) transmitter-receiver pair to communicate over the idle periods of a set of licensed channels, i.e., the primary network. The objective is to maximize data throughput while maintaining the synchronization between secondary users and avoiding interference with licensed (primary) users. No statistical information about the primary traffic is assumed to be available a-priori to the secondary user. We investigate two distinct sensing scenarios. In the first, the secondary transmitter is capable of sensing all the primary channels, whereas it senses one channel only in the second scenario. In both cases, we propose MAC protocols that efficiently learn the statistics of the primary traffic online. Our simulation results demonstrate that the proposed blind protocols asymptotically achieve the throughput obtained when prior knowledge of primary traffic statistics is available.

Mehanna, Omar; Gamal, Hesham El

2008-01-01

307

Rejoining of double strand breaks in normal human and ataxia-telangiectasia fibroblasts after exposure to "6"0Co ?-rays, "2"4"1Am ?-particles or bleomycin  

International Nuclear Information System (INIS)

The rejoining of DNA double strand breaks (dsb) induced by "6"0Co ?-rays, "2"4"1Am ?-particles or bleomycin was measured by neutral filter elution. In agreement with their colony-forming ability, ataxia-telangiectasia cells (AT2BE) and normal fibroblasts exhibited similar dsb rejoining capacity following ?-irradiation, but showed marked differences in the rejoining kinetics of dsb induced by ?-rays or bleomycin. (author)

1987-01-01

308

Security Protocol Design: A Case Study Using Key Distribution Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Nowadays security protocols are a key component in providing security services for fixed and mobile networks. These services include data confidentiality, radio link encryption, message integrity, mobile subscriber authentication, electronic payment, certified e-mail, contract signing and nonrepudiation. This paper is concerned with design of effective security protocols. Security protocols are introduced and some common attacks against security protocols are discussed. The vulnerabilities that lead to theattacks are analyzed and guidelines for effective security protocol design are proposed. The presented guidelines are applied to the Andrew Secure RPC protocol and its adapted versions. It is demonstrated that compliance with the guidelines successfully avoidsfreshness and parallel session attacks.

Reiner Dojen

2009-10-01

309

The use of bleomycin labelled with sup(99m)Tc in the diagnosis of neoplasms of the visual system  

International Nuclear Information System (INIS)

The authors report their preliminary experiences in the following case: choroid malignant melanoma, retinoblastoma, metastatic carcinoma of the iris and retina, and pseudotumour of the orbit. Significant differences were found in accumulation of BLEO sup(99m)Tc between the healthy eye and the eye with malignant melanoma and retinoblastoma, and metastatic carcinoma of the iris. In the investigations with the use of sodium pertechnate such differences were found only in retinoblastoma. In orbital pseudotumour and in metastatic retinal tumour no differences in radioactivity levels were found between the orbits after treatment with cytostatic drugs. Differences were demonstrated between radioactivity distributions in scintigrams of both orbits in cases of very small neoplasms. The method with bleomycin labelled with sup(99m)Tc used for diagnostic purposes was found to be very useful. (author)

1980-01-01

310

Crystallization and preliminary X-ray diffraction studies of bleomycin-binding protein encoded on the transposon Tn5.  

Science.gov (United States)

A bleomycin-binding protein, designated BLMT, encoded on the transposon Tn5 was crystallized using the vapour-diffusion method in a form suitable for X-ray diffraction analysis. Crystals were grown at pH 6.5 in 0.1 M sodium cacodylate and 0.2 M calcium acetate, using 25% PEG 6000 as a precipitant. They belong to the orthorhombic system, space group C2221, with unit-cell dimensions a = 81.56, b = 85.25, c = 78.91 A and one dimer in the asymmetric unit. The diffraction intensity data were collected on beamline 18B of the Photon Factory to 2.0 A resolution with a merging R value of 0.052. The diffraction data set is 91% complete. PMID:10216317

Kumagai, T; Maruyama, M; Matoba, Y; Kawano, Y; Sugiyama, M

1999-05-01

311

Distribution of 67Ga-Bleomycin complex in normal rats and comparison with 67Ga-Cl3  

International Nuclear Information System (INIS)

67Ga- chloride was prepared in Cyclotron Department of Nuclear Research Center of Agriculture and Medicine, then Bleomycin was labeled with 67Ga-Chloride according to the general procedure, but some factors were modified. Distribution of 67 Ca-Bleomycin and 67 Ga-Chloride in 12 tissue of normal rats was studied 1,2, 4, 24 and 48 hours after injection, percent of injection dose per gram of tissue (%ID/g. tissue) in all of 12 normal rats for 67 Ga-Cl3 was lesser than 67Ga-Bl 1,2 and 4 hours after injection, About 67Ga-Bl %ID/g, tissues for bladder was high, because it goes out of body by urine, and there was a high %ID/g, tissue in lung after 1, 2 and 4 hours. About 67GaCl3 likes 67Ga-Bl there was a high %ID/g tissue for bladder, after that was high %ID/g tissue in lung and kidney, too. Also 48 hours after injection, clearance of 67Ga-Bl from blood was 2.64 times that of 67Ga-Cl3 in normal rats and the clearance of 607Ga-Bl in blood from 1 hour till 48 hours after injection to the clearance of 67GaCl3 in blood for above times is about 7 times. They can be reasons that 67Ga does not isolated from 67Ga-Bl complex and not attach to plasma proteins

2002-10-19

312

A family of quantum protocols  

CERN Multimedia

We introduce two dual, purely quantum protocols: for entanglement distillation assisted by quantum communication (``mother'' protocol) and for entanglement assisted quantum communication (``father'' protocol). We show how a large class of ``children'' protocols (including many previously known ones) can be derived from the two by direct application of teleportation or super-dense coding. Furthermore, the parent may be recovered from most of the children protocols by making them ``coherent''. We also summarize the various resource trade-offs these protocols give rise to.

Devetak, I; Winter, A

2003-01-01

313

Bart's Cookbook and Lab Protocols  

Science.gov (United States)

An index of protein biochemistry laboratory protocols and tissue culture techniques. Included are protocols for Immunoprecipitation (IP), Westerns, Angiotensin Protein Kinase Assay, Two Dimensional Peptide Mapping, Phosphaminoacid Analysis, CNBr Mapping, V8 Partial Proteolytic Mapping, Biosynthetic Labeling, Autoradiography, and Fluorography.

2011-06-20

314

Determination of hidden chromosome instability in persons suffered from the action of factors of the Chernobyl accident by the modified 'G2 bleomycin sensitivity assay'  

International Nuclear Information System (INIS)

With the help of the modified 'G2-bleomycin sensitivity assay' the voluntary investigation of hidden chromosome instability in 53 persons with different radiation exposures had been fulfilled. In all examined groups, the individual levels of chromosome injuries under identical bleomycin exposure varied in a wide range and didn't depend on their initial values in intact cultures. Among control donors and individuals with low radiation exposure, ? 33 % hypertensive persons had been identified that can be considered as a genetically caused phenomenon. In patients recovered from acute radiation, 57.9 % persons expressed the hidden chromosome instability. The data obtained allow us to assume that high doses of ionizing radiation can modify the inherited susceptibility of human chromosomes to a mutagen exposure.

2009-01-01

315

Influence of radiotherapy upon tumor accumulation and organ distribution of 57Co-bleomycin in mice with chemically induced squamous cell carcinoma  

International Nuclear Information System (INIS)

Squamous cell carcinoma was induced in male 6 to 8-week old NMRI-mice by application of 9,10-dimethyl-1,2-benzanthracene on the skin. 15 weeks later macroscopically visible skin tumors are developed. Then organ distribution and tumor accumulation of 57Co-Bleomycin (spec. activity 1 mCi/3.3 mg) were studied 1 to 48 hours after injection. In squamous cell carcinoma a high uptake of this tumor-seeking agent can be demonstrated (n = 46). After radiotherapy (100 kV; 1.7 mm Al-filter; 18.8 Gy)(n=26), however, a significantly reduced uptake of 57Co-Bleomycin in tumor tissue is observed. Possible consequences from these animal studies for tumor scintigraphy with this radiopharmaceutical in man are discussed. (orig.)

1979-11-01

316

Mitosis Methods & Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Mitosis Methods & Protocols Andrew D. McAinsh (Edt Humana press, Totowa, New Jersey (USA Series: Springer Protocols Methods in Molecular Biology, Volume 545, 2009 ISBN: 978-1-60327-992-5   It is quite clear from the contents of this book that the remarkably fascinating phenomenon of mitosis (that captured, and still is capturing, the attention of entire generations of scientists is still open to research. This is mainly due to our lack of knowledge of so many multifaced events of this extraordinarly complex process. The reader giving a glace through the Contents and Contributors sections is speechless: All of the first-class models (i.e., budding yeast, Caenorabditis, Drosophila, Xenopus and Human are presented..... 

CarloAlberto Redi

2010-06-01

317

Protocols for distributive scheduling  

Science.gov (United States)

The increasing complexity of space operations and the inclusion of interorganizational and international groups in the planning and control of space missions lead to requirements for greater communication, coordination, and cooperation among mission schedulers. These schedulers must jointly allocate scarce shared resources among the various operational and mission oriented activities while adhering to all constraints. This scheduling environment is complicated by such factors as the presence of varying perspectives and conflicting objectives among the schedulers, the need for different schedulers to work in parallel, and limited communication among schedulers. Smooth interaction among schedulers requires the use of protocols that govern such issues as resource sharing, authority to update the schedule, and communication of updates. This paper addresses the development and characteristics of such protocols and their use in a distributed scheduling environment that incorporates computer-aided scheduling tools. An example problem is drawn from the domain of space shuttle mission planning.

Richards, Stephen F.; Fox, Barry

1993-01-01

318

Peptidomics - Methods and protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Nearly ten years ago the scientific community added another discipline to the big –omics family, peptidomics, i.e., “the study of the complement of peptides from a cell, organelle, tissue or organism”. This fact derives from the exceptional capacity to produce data by high-throughput techniques and machines that allow us to pass from proteomics analysis of complex biological systems to the capacity to resolve their peptides content even at the single cell level. Thus, the time is set to have this Peptidomics: Methods and protocols edited by Mikhail Soloviev. I think the editor did a great job; I was reading a very usefull book, a great collection of protocols (that widely range as for the organisms studied, from Bacteria to Man ! both for those are newcomer potential users, as I am, and for those are already acquiented to .....

CarloAlberto Redi

2010-09-01

319

Password Guessing Resistant Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available Attacks on passwords are increasing day by day. Brute force attack and dictionary attacks are the well known attacks. Automated Turing Test is effective approach to minimize such attacks and identify malicious logins. But sometimes it may create inconvenience to the authorized user as the user always has to cross or go through the ATTs. So to avoid such inconvenience, a new technique called Password Guessing Resistant Protocol (PGRP is introduced. It overcomes the drawbacks of existing protocols like Pinkas and Sander. PGRP limit the total number of login attempts from unknown source IP address as low as three attempts and the user can make five failed login from the known and frequently used system. CAPTCHA, used is text based, logical and can also be image based. This could make the password guessing more difficult by the automated programs. Multiple ATTs are used to increase the security.

Arya Kumar

2014-02-01

320

Effects of four chemotherapeutic agents, bleomycin, Etoposide, Cisplatin, and cyclophosphamide, on DNA damage and telomeres in a mouse spermatogonial cell line.  

Science.gov (United States)

Treatment with chemotherapeutics agents may induce persistent DNA damage in male germ cells with the possibility of long-term consequences on fertility and progeny outcome. Telomeres, specialized structures at the physical ends of chromosomes, play an important role in the maintenance of genetic stability and in the response of somatic cells to anticancer drugs. Our objective was to test the hypothesis that exposure to bleomycin, etoposide, or cisplatin (the drugs used to treat testicular cancer) or cyclophosphamide (an anticancer agent and immunosuppressant) targets telomeres in the male germ line. C18-4 spermatogonial cells were exposed to bleomycin, etoposide, cisplatin, or 4-hydroperoxycyclophosphamide (4OOH-CPA, a preactivated analog of cyclophosphamide). All four anticancer drugs induced a significant increase in DNA damage in C18-4 cells, as assessed by gamma-H2AX immunofluorescence. Interestingly, the gamma-H2AX signal was localized to telomeres after treatment with bleomycin, cisplatin, and 4OOH-CPA, but not etoposide. Mean telomere lengths, the intensity of the telomere fluorescence in situ hybridization signal, telomerase activity, and the expression of the telomerase enzyme mRNA components, Tert and Terc, were reduced by exposure to cisplatin and 4OOH-CPA, but not by bleomycin or etoposide. Thus, although all four anticancer drugs induced DNA damage in this spermatogonial cell line, telomeres were not specifically affected by etoposide and only the two alkylating agents, cisplatin and 4OOH-CPA, induced telomere dysfunction. This telomere dysfunction may contribute to infertility and developmental defects in the offspring. PMID:24571982

Liu, Mingxi; Hales, Barbara F; Robaire, Bernard

2014-01-01

 
 
 
 
321

Escleroterapia con bleomicina en malformaciones vasculares de bajo flujo: Experiencia y revisión del tema Bleomycin sclerotherapy for low-flow vascular malformations: our experience and literature review  

Directory of Open Access Journals (Sweden)

Full Text Available Las anomalías vasculares son lesiones típicas de los pacientes pediátricos y se dividen en dos categorías: tumores vasculares y malformaciones vasculares de alto y bajo flujo. Estas últimas pueden tratarse de diversos modos: laserterapia, drenaje, aspiración, cirugía o escleroterapia, dependiendo del tipo de lesión y de su localización. Entre los agentes esclerosantes utilizados, la bleomicina ha demostrado tener buenos resultados en el tratamiento de estas lesiones. En este artículo presentamos nuestra experiencia en el tratamiento de las malformaciones vasculares de bajo flujo mediante escleroterapia con bleomicina intralesional. Desarrollamos un estudio descriptivo retrospectivo sobre 30 pacientes que presentaban malformación vascular de bajo flujo y fueron tratados con bleomicina intralesional. Los resultados fueron buenos o excelentes en 22 pacientes y regulares o malos en los 8 restantes. De acuerdo a nuestra casuística y a la literatura revisada, la escleroterapia con bleomicina es una alternativa terapéutica eficaz y segura en el tratamiento de las malformaciones vasculares de bajo flujo.Vascular anomalies are common in children and can be divided into two categories, vascular tumours and vascular malformations: high-flow or low-flow. The latter can be treated in different ways such as lasertherapy, drainage, aspiration, surgery or sclerotherapy depending on the type and location of the lesion. Among the accepted sclerosing agents, bleomycin has proven good results in the treatment of this condition. Herein we present our experience in the treatment of low-flow vascular malformations with intralesional bleomycin injection. This is a retrospective, descriptive study with 30 patients presenting a low-flow vascular malformation treated with intralesional bleomycin injection. Our results are good or excellent in 22 patients and poor in the other 8. According to our case series and the consulted literature, sclerotherapy with intralesional bleomycin injection is an effective and safe treatment for low-flow vascular malformations.

F. Lobo Bailón

2012-12-01

322

Escleroterapia con bleomicina en malformaciones vasculares de bajo flujo: Experiencia y revisión del tema / Bleomycin sclerotherapy for low-flow vascular malformations: our experience and literature review  

Scientific Electronic Library Online (English)

Full Text Available SciELO Spain | Language: Spanish Abstract in spanish Las anomalías vasculares son lesiones típicas de los pacientes pediátricos y se dividen en dos categorías: tumores vasculares y malformaciones vasculares de alto y bajo flujo. Estas últimas pueden tratarse de diversos modos: laserterapia, drenaje, aspiración, cirugía o escleroterapia, dependiendo de [...] l tipo de lesión y de su localización. Entre los agentes esclerosantes utilizados, la bleomicina ha demostrado tener buenos resultados en el tratamiento de estas lesiones. En este artículo presentamos nuestra experiencia en el tratamiento de las malformaciones vasculares de bajo flujo mediante escleroterapia con bleomicina intralesional. Desarrollamos un estudio descriptivo retrospectivo sobre 30 pacientes que presentaban malformación vascular de bajo flujo y fueron tratados con bleomicina intralesional. Los resultados fueron buenos o excelentes en 22 pacientes y regulares o malos en los 8 restantes. De acuerdo a nuestra casuística y a la literatura revisada, la escleroterapia con bleomicina es una alternativa terapéutica eficaz y segura en el tratamiento de las malformaciones vasculares de bajo flujo. Abstract in english Vascular anomalies are common in children and can be divided into two categories, vascular tumours and vascular malformations: high-flow or low-flow. The latter can be treated in different ways such as lasertherapy, drainage, aspiration, surgery or sclerotherapy depending on the type and location of [...] the lesion. Among the accepted sclerosing agents, bleomycin has proven good results in the treatment of this condition. Herein we present our experience in the treatment of low-flow vascular malformations with intralesional bleomycin injection. This is a retrospective, descriptive study with 30 patients presenting a low-flow vascular malformation treated with intralesional bleomycin injection. Our results are good or excellent in 22 patients and poor in the other 8. According to our case series and the consulted literature, sclerotherapy with intralesional bleomycin injection is an effective and safe treatment for low-flow vascular malformations.

Lobo Bailón, F.; Berenguer Fröhner, B.; González Meli, B.; Marín Molina, C.; De Tomás y Palacios, E.; Alonso Bañuelos, C..

323

Redox imbalance and pulmonary function in bleomycin-induced fibrosis in C57BL/6, DBA/2, and BALB/c mice.  

Science.gov (United States)

The development of bleomycin-induced pulmonary fibrosis (BLEO-PF) has been associated with differences in genetic background and oxidative stress status. The authors' aim was to investigate the crosstalk between the redox profile, lung histology, and respiratory function in BLEO-PF in C57BL/6, DBA/2, and BALB/c mice. BLEO-PF was induced with a single intratracheal dose of bleomycin (0.1 U/mouse). Twenty-one days after bleomycin administration, the mortality rate was over 50% in C57BL/6 and 20% in DBA/2 mice, and BLEO-PF was not observed in BALB/c. There was an increase in lung static elastance (p < .001), viscoelastic/inhomogeneous pressure (p < .05), total pressure drop after flow interruption (p < .01), and ?E (p < .05) in C57BL/6 mice. The septa volume increased in C57BL/6 (p < .05) and DBA/2 (p < .001). The levels of IFN-? were reduced in C57BL/6 mice (p < .01). OH-proline levels were increased in C57BL/6 and DBA/2 mice (p < .05). SOD activity and expression were reduced in C57BL/6 and DBA/2 mice (p < .001 and p < .001, respectively), whereas catalase was reduced in all strains 21 days following bleomycin administration compared with the saline groups (C57BL/6: p < .05; DBA/2: p < .01; BALB/c: p < .01). GPx activity and GPx1/2 expression decreased in C57BL/6 (p < .001). The authors conclude that BLEO-PF resistance may also be related to the activity and expression of SOD in BALB/c mice. PMID:22549973

Santos-Silva, Marco Aurélio; Pires, Karla Maria Pereira; Trajano, Eduardo Tavares Lima; Martins, Vanessa; Nesi, Renata Tiscoski; Benjamin, Cláudia Farias; Caetano, Maurício Silva; Sternberg, Cinthya; Machado, Mariana Nascimento; Zin, Walter Araújo; Valença, Samuel Santos; Porto, Luis Cristóvão

2012-07-01

324

Induction of micronuclei in CHO cells by bleomycin but not by X-irradiation is decreased by treatment with HMG-CoA reductase inhibitors  

International Nuclear Information System (INIS)

We investigated the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and fluvastatin, on the induction of micronuclei by ionizing radiation or bleomycin in Chinese hamster ovary cells in order to assess the radical-scavenging ability of these inhibitors. The results indicated that both pravastatin and fluvastatin had no effect on the induction of micronuclei by X-irradiation when they were applied for either pre-treatment or post-treatment. In contrast, both drugs effectively reduced the frequency of bleomycin-induced micronuclei when they were applied for simultaneous treatment or post-treatment, but not for pre-treatment. This indicates that the radical-scavenging ability of these two HIMG-CoA reductase inhibitors differs according to the origins of the radicals, e.g., X-rays or bleomycin, even when the two drugs are compared at an equivalent cytotoxic dose. Our results suggest that both pravastatin and fluvastatin have the ability to scavenge certain types of radicals and to protect cells against oxidative stress. (author)

2005-06-01

325

Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin, and the tumor promoter 12-O-tetradecanoylphorbol 13-acetate  

International Nuclear Information System (INIS)

Using short-term cultures of hamster embryo cells, we have examined the effects of the free-radical scavenger superoxide dismutase (superoxide:superoxide oxidoreductase, EC 1.15.1.1) and the enzyme catalase (hydrogen-peroxide:hydrogen-peroxide oxidoreductase, EC 1.11.1.6) on x-ray-and bleomycin-induced transformation and on the enhancement of radiogenic transformation by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA). We find that superoxide dismutase inhibits (i) transformation induced by x-ray and bleomycin and (ii) promotional action of TPA in vitro. The results suggest that the oncogenic action of x-rays and bleomycin and the enhancement of oncogenic transformation by TPA are mediated in part by free radicals. The findings also suggest that superoxide dismutase can serve as an inhibitor of oncogenesis and that its actions, as seen in this in vitro system, are most predominantly on inhibiting late events in the progression of cellular transformation--those associated with promotion

1983-01-01

326

A protected password change protocol  

CERN Document Server

Some protected password change protocols were proposed. However, the previous protocols were easily vulnerable to several attacks such as denial of service, password guessing, stolen-verifier and impersonation atacks etc. Recently, Chang et al. proposed a simple authenticated key agreement and protected password change protocol for enhancing the security and efficiency. In this paper, authors shall show that password guessing, denial of service and known-key attacks can work in their password change protocol. At the same time, authors shall propose a new password change protocol to withstand all the threats of security.

Wang, R C; Mo, K R; Wang, Ren-Chiun; Yang, Chou-Chen; Mo, Kun-Ru

2005-01-01

327

Communication complexity protocols for qutrits  

International Nuclear Information System (INIS)

Consider a function where its entries are distributed among many parties. Suppose each party is allowed to send only a limited amount of information to a referee. The referee can use a classical protocol to compute the value of the global function. Is there a quantum protocol improving the results of all classical protocols? In a recent work Brukner et al. showed the deep connection between such problems and the theory of Bell inequalities. Here we generalize the theory to trits. There, the best classical protocol fails whereas the quantum protocol yields the correct answer

2007-03-01

328

Impersonation Attack on EKE Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available The key exchange protocol is one of the most elegant ways of establishing secure communication between pair of users by using a session key. The passwords are of low entropy, hence the protocol should resist all types of password guessing attacks. Recently ECC-3PEKE protocol has been proposed by Chang and Chang. They claimed the protocol is secure, efficient and practical. Unless their claims Yoon and Yoo presented an Undetectable online password guessing attack on the above protocol. A key recovery attack was proved on ECC-3PEKE protocol using the Undetectable online password guessing attack proposed by Yoon and Yon. In the present paper an Impersonation attack on ECC-3PEKE protocol using the Undetectable online password guessing attack proposed by Yoon and Yon is demonstrated

Shirisha Tallapally

2010-04-01

329

Address Resolution Protocol Optimization  

Directory of Open Access Journals (Sweden)

Full Text Available This paper proposes an improved Address Resolution Protocol (ARP for Ethernet-based networks. Inthe proposed alternative method, the ARP request packets are not broadcasted but instead unicastedto an ARP server which will have all the mappings of all the hosts connected to the network.This significantly reduces ARP signaling and processing overhead. The ARP server obtains the mappingsthrough a novel passive method that does not introduce additional overhead in the network. Furthermore,the use of the ARP server makes it much easier to secure the network against certain attacks like ARPpoisoning.

Nor Adnan Yahaya

2009-09-01

330

FRENCH PROTOCOL CARDS  

CERN Document Server

Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

Division du Personnel

1999-01-01

331

FRENCH PROTOCOL CARDS  

CERN Multimedia

Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.

Division des Ressources Humaines; Human Resources Division; Tel. 74683-79494

2000-01-01

332

Hektoen Enteric Agar Protocol  

Science.gov (United States)

Hektoen enteric agar is a selective and differential media for the recovery of enteric gram-negative rods from mixed microbiota.  The growth of gram-positive organisms and nonpathogenic enteric coliforms is inhibited through the use of bile salts and dyes, allowing intestinal pathogens, such as Salmonella and Shigella, to be more easily recovered.  The media can also differentiate between organisms that produce H2S and those that do not due to the presence of an iron-containing compound.  The use and interpretation of growth on this media is discussed in this protocol.

American Society For Microbiology;

2010-11-11

333

Security and SCADA protocols  

International Nuclear Information System (INIS)

Supervisory control and data acquisition (SCADA) networks have replaced discrete wiring for many industrial processes, and the efficiency of the network alternative suggests a trend toward more SCADA networks in the future. This paper broadly considers SCADA to include distributed control systems (DCS) and digital control systems. These networks offer many advantages, but they also introduce potential vulnerabilities that can be exploited by adversaries. Inter-connectivity exposes SCADA networks to many of the same threats that face the public internet and many of the established defenses therefore show promise if adapted to the SCADA differences. This paper provides an overview of security issues in SCADA networks and ongoing efforts to improve the security of these networks. Initially, a few samples from the range of threats to SCADA network security are offered. Next, attention is focused on security assessment of SCADA communication protocols. Three challenges must be addressed to strengthen SCADA networks. Access control mechanisms need to be introduced or strengthened, improvements are needed inside of the network to enhance security and network monitoring, and SCADA security management improvements and policies are needed. This paper discusses each of these challenges. This paper uses the Profibus protocol as an example to illustrate some of the vulnerabilities that arise within SCADA networks. The example Profibus security assessment establishes a network model and an attacker model before proceeding to a list of example attacks. (authors)

2006-11-12

334

Stream Control Transmission Protocol Steganography  

CERN Document Server

Stream Control Transmission Protocol (SCTP) is a new transport layer protocol that is due to replace TCP (Transmission Control Protocol) and UDP (User Datagram Protocol) protocols in future IP networks. Currently, it is implemented in such operating systems like BSD, Linux, HP-UX or Sun Solaris. It is also supported in Cisco network devices operating system (Cisco IOS) and may be used in Windows. This paper describes potential steganographic methods that may be applied to SCTP and may pose a threat to network security. Proposed methods utilize new, characteristic SCTP features like multi-homing and multistreaming. Identified new threats and suggested countermeasures may be used as a supplement to RFC 5062, which describes security attacks in SCTP protocol and can induce further standard modifications.

Fraczek, Wojciech; Szczypiorski, Krzysztof

2010-01-01

335

On Ultralightweight RFID Authentication Protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

A recent research trend, motivated by the massive deployment of RFID technology, looks at cryptographic protocols for securing communication between entities in which some of the parties have very limited computing capabilities. In this paper, we focus our attention on SASI, a new RFID authentication protocol, designed for providing Strong Authentication and Strong Integrity. SASI is a good representative of a family of RFID authentication protocols, referred to as Ultralightweight RFID authe...

D Apos Arco, Paolo; Santis, Alfredo

2011-01-01

336

A Routing Protocol for MANETs  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In this master thesis there has been a description of what MANETs are and why they are so interesting. Because of its characteristics, the tradicional routing protocols for wired networks are not advisable for them. A specific routing protocol for MANETs is necessary. In this thesis the main groups of these protocols have been explained and some of the most commonly used of them were studied. We saw that each protocol is better in a specific environment. None of them are perfect for all...

2007-01-01

337

A Routing Protocol for MANETs  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In this master thesis there has been a description of what MANETs are and why they are so interesting. Because of its characteristics, the tradicional routing protocols for wired networks are not advisable for them. A specific routing protocol for MANETs is necessary. In this thesis the main groups of these protocols have been explained and some of the most commonly used of them were studied. We saw that each protocol is better in a specific environment. None of them are perfect for all the r...

2007-01-01

338

Topics in free radical-mediated DNA damage: purines and damage amplification - superoxic reactions - bleomycin, the incomplete radiomimetic  

Energy Technology Data Exchange (ETDEWEB)

Only a small percentage of the DNA damage set by ionizing radiation in the living cell manifests itself as lethal. It is now increasingly accepted that clustered lesions may constitute the kind of damage that the repair enzymes cannot adequately deal with. The question is raised as to whether damage amplification reactions (radical transfer reactions) may contribute to these clustered lesions, and examples of such damage amplification reactions are given. In one example a purine is involved. With 2'-deoxy adenosine and 2'-deoxy guanosine it is shown that these purine nucleosides undergo unexpected radical reactions. Evidence for the radical transfer from the purine to the sugar moiety is provided by the formation of the 5'-aldehydes. These products have been assayed with 2-thiobarbituric acid (TBA), a reagent commonly applied to the detection of malonaldehyde. TBA-reactive material has also been assayed in [gamma]-irradiated DNA, about one-third of this is free malonaldehyde, while the major part of the TBA-reactive material remains bound to the DNA. In contrast, bleomycin-treated DNA yields practically no free malonaldehyde, and the major TBA-reactive products are identified as the thymine and adenine base propenals. (Author).

Sonntag, C. von (Max-Planck-Institut fuer Strahlenchemie, Muelheim an der Ruhr (Germany))

1994-11-01

339

X-ray-sensitive mutants of mouse mammary carcinoma cells are hypersensitive to bleomycin and hydrogen peroxide  

International Nuclear Information System (INIS)

Radiation-sensitive mutants, SX9 and SX10, were isolated from mouse mammary carcinoma FM3A cells. The mutant SX9 complemented another radiation-sensitive strain M10 of mouse leukemia L5178Y cells, but SX10 did not. SX9 and SX10 cells were more sensitive than the wild-type cells to the lethal effects of bleomycin. The frequency of X-ray-induced mutations to 6-thioguanine resistance was much higher in SX9 cells than in the wild-type cells in the dose range up to 1 Gy, although the induced mutant frequencies were not very different between these two cell strains when compared at equivalent survival. SX9, SX10 and M10 cells were found to be far more sensitive than the respective wild-type cells to hydrogen peroxide inactivation, but the levels of catalase activity were similar among these cell strains. These mutants should be useful for cloning and identifying the human genes responsible for radiation sensitivity. (author)

1986-01-01

340

Modification of bleomycin-induced chromosome aberrations by hyperthermia and under energy depleting conditions in human peripheral lymphocytes  

International Nuclear Information System (INIS)

Synergistic effects of bleomycin (BLM) and hyperthermia were studied in human peripheral lymphocytes (HPL). The frequencies of breaks produced by BLM were dependent on dose, incubation temperature, and treatment time. Heat alone did not induce chromosome aberrations. Synergistic effects of heat and BLM occurred at 43oC, either when hyperthermia was for 60 min following treatment with BLM or for 30 min simultaneously with BLM treatment. At incubation temperatures below 43oC as may dicentric chromosomes as chromosome breaks were found, but about twice as many dicentric chromosomes as chromosome breaks were found when cells were treated with BLM at 43oC for 60 min. In all experiments with BLM chromosomal anomalies were overdispersed. Comparison with unstimulated HPL, heated after X-irradiation, suggested that heat inhibits repair of BLM-induced lesions to a smaller extent than X-ray-induced lesions. Experiments with sodium azide and 2-deoxyglucose led to the conclusion that cellular uptake of BLM is partly energy-dependent. Additionally, an energy-independent uptake of BLM, not blocked by inhibitors, was apparent. (Author)

1992-09-01

 
 
 
 
341

Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina  

International Nuclear Information System (INIS)

Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals

2008-03-01

342

Killing of human lung cancer cells using a new [111In]bleomycin complex [111In]BLMC  

International Nuclear Information System (INIS)

The ability of a [111In]bleomycin complex [(111In]BLMC) to kill five cell lines of human lung cancer (small cell lung cancer) was investigated. Cells were exposed to either 0.9% NaCl, [111In]Cl3, BLM, [111In]BLMC, nonradioactive InCl3, or In-BLMC for 60 minutes, plated in soft agarose, and assessed for colony formation. [111In]BLMC (40-200 microCi carried by 15-25 micrograms BLM/ml) was more cytotoxic than BLM (15-25 micrograms BLM/ml) by a factor of 1.6-5.3 for five cell lines. The percent survival of N417 cells was 28.4 for [111In]BLMC (40 microCi/15 micrograms BLM/ml) and 54.3 for BLM (15 micrograms/ml); 1.9 for [111In]BLMC (200 microCi/25 micrograms BLM/ml), and 10.0 for BLM (25 micrograms/ml). 111InCl3 (200 microCi/ml) and nonradioactive InCl3 failed to inhibit colony formation. The new [111In]BLMC may be useful for therapy of some lung cancer patients

1989-01-01

343

Melatonin Inhibits Endoplasmic Reticulum Stress and Epithelial-Mesenchymal Transition during Bleomycin-Induced Pulmonary Fibrosis in Mice.  

Science.gov (United States)

Several reports indicate that melatonin alleviates bleomycin (BLM)-induced pulmonary fibrosis in rodent animals. Nevertheless, the exact mechanism remains obscure. The present study investigated the effects of melatonin on endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) during BLM-induced lung fibrosis. For the induction of pulmonary fibrosis, mice were intratracheally injected with a single dose of BLM (5.0 mg/kg). Some mice were intraperitoneally injected with melatonin (5 mg/kg) daily for a period of 3 wk. Twenty-one days after BLM injection, lung fibrosis was evaluated. As expected, melatonin significantly alleviated BLM-induced pulmonary fibrosis, as evidenced by Sirius red staining. Moreover, melatonin significantly attenuated BLM-induced EMT to myofibroblasts, as determined by its repression of ?-SMA expression. Further analysis showed that melatonin markedly attenuated BLM-induced GRP78 up-regulation and elevation of the cleaved ATF6 in the lungs. Moreover, melatonin obviously attenuated BLM-induced activation of pulmonary eIF2?, a downstream target of the PERK pathway. Finally, melatonin repressed BLM-induced pulmonary IRE1? phosphorylation. Correspondingly, melatonin inhibited BLM-induced activation of XBP-1 and JNK, two downstream targets of the IRE1 pathway. Taken together, these results suggest that melatonin alleviates ER stress and ER stress-mediated EMT in the process of BLM-induced pulmonary fibrosis. PMID:24818755

Zhao, Hui; Wu, Qing-Qing; Cao, Lin-Feng; Qing, Hou-Ying; Zhang, Cheng; Chen, Yuan-Hua; Wang, Hua; Liu, Rong-Ru; Xu, De-Xiang

2014-01-01

344

In vivo biodistribution of 131I labeled bleomycin (BLM) and isomers (A2 and B2) on experimental animal models  

International Nuclear Information System (INIS)

Bleomycins (BLMs; BLM, A2, and B2) were labeled with 131I and radiopharmaceutical potentials were investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography (TLRC), high performance liquid chromatography (HPLC), and liquid chromatography (LC/MS/MS). Labeling yields of radiolabeled BLMs were found to be 90, 68, and 71%, respectively. HPLC chromatograms were taken for BLM and cold iodinated BLM (127I-BLM). Five peaks were detected for BLM and three peaks for 127I-BLM in the HPLC studies. Two peaks belong to isomers of BLM. The isomers of BLM were purified with using HPLC. Biological activity of BLM was determined on male Albino Wistar rats by biodistribution and scintigraphic studies were performed for BLMs by using New Zealand rabbits. The biodistribution results of 131I-BLM showed high uptake in the stomach, the bladder, the prostate, the testicle, and the spinal cord in rats. Scintigraphic results on rabbits agrees with that of biodistributional studies on rats. The scintigraphy of radiolabeled isomers (131I-A2 and 131I-B2) are similarly found with that of 131I-BLM. (author)

2010-07-01

345

Gamma rays and bleomycin nick DNA and reverse the DNase I sensitivity of beta-globin gene chromatin in vivo  

International Nuclear Information System (INIS)

The active beta-globin genes in chicken erythrocytes, like all active genes, reside in large chromatin domains which are preferentially sensitive to digestion by DNase I. We have recently proposed that the special structure of chromatin in active domains is maintained by torsional stress in the DNA. This hypothesis predicts that nicking of the DNA within any such chromosomal domain in vivo will relax the DNA and lead to loss of the special DNase I-sensitive state. Here we have tested this prediction by using gamma irradiation and bleomycin treatment to cleave DNA within intact chicken embryo erythrocytes. Both treatments cause reversal of DNase I sensitivity. Moreover, reversal occurs at approximately one nick per 150 kilobase pairs for both agents despite their entirely unrelated modes of cell penetration and DNA attack. These results suggest that the domain of DNase I sensitivity surrounding the beta-globin genes comprises 150 kilobase pairs of chromatin under torsional stress and that a single DNA nick in this region is sufficient to reverse the DNase I sensitivity throughout the entire domain

1987-01-01

346

Assessment of cobalt 57 tagged bleomycin as a clinical aid in staging of head and neck carcinoma  

International Nuclear Information System (INIS)

Critical assessment of head and neck cancer with respect to staging has, on occasion, been disappointingly ineffective. We have attempted to correlate the incidence of measureable uptake of cobalt 57 tagged bleomycin by primary squamous cell carcinoma and metastatic cervical lymph nodes. Forty-six cases have been evaluated with respect to histopathological confirmation of the suspected metastatic disease. We have found that this diagnostic measure increases our acumen in staging of head and neck cancer. The relevance of the Co-Bleo scans as a diagnostic aid is reported in 46 cases. Malignant tumors greater than 2 cm in size appear to demonstrate active uptake of the imaging agent. Small tumor size and excess background radioactivity contribute to the false-negatives (17%). Inflammatory conditions or benign tumors of the salivary apparatus may result in minimal uptake, thus, a false-positive result (10%). An increase in the radioactivity of the Co-Bleo may enhance the benefits of this procedure in the search for an undiagnosed primary, as well as undiagnosed local or distant metastases

1981-01-01

347

Assessment of cobalt 57 tagged bleomycin as a clinical aid in staging of head and neck carcinoma  

International Nuclear Information System (INIS)

Critical assessment of head and neck cancer with respect to staging has, on occasion, been disappointingly ineffective. The incidence of measurable uptake of cobalt 57 tagged bleomycin by primary squamous cell carcinoma and metastatic cervical lymph nodes has been correlated. Forty-six cases have been evaluated with respect to histopathological confirmation of the suspected metastatic disease. We have found that this diagnostic measure increases our acumen in staging of head and neck cancer. The relevance of the Co-Bleo scans as a diagnostic aid is reported in 46 cases. Malignant tumors greater than 2 cm in size appear to demonstrate active uptake of the imaging agent. Small tumor size and excess background radioactivity contribute to the false-negatives (17%). Inflammatory conditions or benign tumors of the salivary apparatus may result in minimal uptake, thus, a false-positive result (10%). An increase in the radioactivity of the Co-Bleo may enhance the benefits of this procedure in the search for an undiagnosed primary, as well as undiagnosed local or distant metastases

1981-01-01

348

Topics in free radical-mediated DNA damage: purines and damage amplification - superoxic reactions - bleomycin, the incomplete radiomimetic  

International Nuclear Information System (INIS)

Only a small percentage of the DNA damage set by ionizing radiation in the living cell manifests itself as lethal. It is now increasingly accepted that clustered lesions may constitute the kind of damage that the repair enzymes cannot adequately deal with. The question is raised as to whether damage amplification reactions (radical transfer reactions) may contribute to these clustered lesions, and examples of such damage amplification reactions are given. In one example a purine is involved. With 2'-deoxy adenosine and 2'-deoxy guanosine it is shown that these purine nucleosides undergo unexpected radical reactions. Evidence for the radical transfer from the purine to the sugar moiety is provided by the formation of the 5'-aldehydes. These products have been assayed with 2-thiobarbituric acid (TBA), a reagent commonly applied to the detection of malonaldehyde. TBA-reactive material has also been assayed in ?-irradiated DNA, about one-third of this is free malonaldehyde, while the major part of the TBA-reactive material remains bound to the DNA. In contrast, bleomycin-treated DNA yields practically no free malonaldehyde, and the major TBA-reactive products are identified as the thymine and adenine base propenals. (Author)

1994-11-01

349

Autonomic MANET Routing Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available In Mobile Ad hoc Networks (MANETs, timers have been used widely to maintain routing (state information. The use of fixed-interval timers is simple to implement but, in practise, may be difficult to configure in dynamic operational environments, and so may give reduced performance in the presence of frequent topology changes. This paper proposes a self-tuning timer approach within a simple control system for MANET routing protocols with the aim of allowing dynamic, autonomic, re-calibration of routing update frequencies. A novel dynamic timer algorithm is presented to automatically tune routing performance by adapting timer intervals to network conditions. Our simulation results have shown that, compared to the default fixed timer approach, the proposed algorithm could effectively improve routing throughput without manual configuration.

Saleem Bhatti

2009-10-01

350

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

The iDct-GFP mice (01XT4) contain two transgenes, so two genotyping PCR reactions need to be run for each mouse. The genotyping PCR protocol 1 is used to type the Dct-rtTA gene and protocol 2 is forTRE-H2BGFP gene.

351

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

ICR-Tg(GFAP-CDK4)2Gtm/Nci PCR Protocol Strain: ICR-Tg(GFAP-CDK4)2Gtm/Nci Strain Code: 01XK1 Protocol Number: 1 Introductory Comment: The primer set was taken from the following published paper: Oncogene 21:1325-1334. The primer set amplifies the GFAP

352

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

B6;129-Myf6tm2(cre)Mrc/Nci PCR Protocol Strain: B6;129-Myf6tm2(cre)Mrc/Nci Strain Code: 01XBL Protocol Number: 1 Introductory Comment: Primers:  ck219 :   5'-CTTCAGCGCCTTTCTTCCATCG -3'  ba88 :   5'-GAACTTCGTTTGCAACTGAC -3'  ba86 :   5'-GGATAGTGAAACAGGGCAA

353

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

FVB/N-Tg(Tyr-HRAS)60Lc/Nci PCR Protocol Strain: FVB/N-Tg(Tyr-HRAS)60Lc/Nci Strain Code: 01XB5 Protocol Number: 1 Introductory Comment: Primers:  H001 :   5'-cAG ATc AAA cGG GTG AAG G -3'  H002 :   5'-GTc TTG Gcc GAG GTc TcG -3' Product Sizes:   Primer

354

About the Protocol Information Office  

Science.gov (United States)

About the Protocol Information Office Protocol Information Office Staff See contact information, room numbers, and more on the Staff Directory in the About DCP section. Anne Tompkins, RN, MSNHead E-mail: tompkinsa@mail.nih.gov Phone: (240) 276-7130

355

Medium Access Control Protocols With Memory  

CERN Multimedia

We propose a class of distributed medium access control protocols that utilize memory about users' transmission decisions and feedback information. We consider a slotted Aloha system and define protocols with memory. We introduce two performance metrics, total throughput and average expected delay, and formulate the problem faced by a protocol designer of finding an optimal protocol. Incentive compatibility constraints can be imposed on the protocol designer's problem when users can manipulate prescribed protocols. We first show that we can achieve time division multiple access using protocols with sufficiently long memory. Next we analyze the performance of protocols with memory 1 (i.e., memory for one slot) using the Markov model and numerical methods. Compared to protocols without memory, protocols with memory 1 yield smaller average expected delay for a given level of total throughput that can be attained by a protocol without memory. Moreover, using protocols with memory 1, the protocol designer can achi...

Park, Jaeok

2009-01-01

356

Oxidation of the sugar moiety of DNA by ionizing radiation or bleomycin could induce the formation of a cluster DNA lesion.  

Science.gov (United States)

Bleomycin, a radiomimetic drug currently used in human cancer therapy, is a well known carcinogen. Its toxicity is mostly attributed to its potentiality to induce DNA double strand breaks likely arising from the formation of two vicinal DNA strand breaks, initiated by C4-hydrogen abstraction on the 2-deoxyribose moiety. In this work we demonstrate that such a hydrogen abstraction reaction is able to induce the formation of a clustered DNA lesion, involving a 3' strand break together with a modified sugar residue exhibiting a reactive alpha,beta-unsaturated aldehyde that further reacts with a proximate cytosine base. The lesion thus produced was detected as a mixture of four isomers by HPLC coupled to tandem mass spectrometry subsequent to DNA extraction and enzymatic digestion. The modified nucleosides that constitute new types of cytosine adducts were identified as the likely two pairs of diastereomers of 6-(2-deoxy-beta-D-erythro-pentofuranosyl)-2-hydroxy-3(3-hydroxy-2-oxopropyl)-2,6-dihydroimidazo[1,2-c]-pyrimidin-5(3H)-one as inferred from mass spectrometry and NMR analyses of the chemically synthesized nucleosides. We demonstrate that bleomycin, and to a minor extent ionizing radiation, are able to induce significant amounts of the cytosine damage in cellular DNA. In addition, the repair kinetic of the lesion in a human lymphocyte cell line is rather slow, with a half-life of 10 h. The 2'-deoxycytidine adducts thus characterized that represent the first example of complex DNA lesions isolated and identified in cellular DNA upon one radical hit are likely to play an important role in the toxicity of bleomycin. PMID:17715301

Regulus, Peggy; Duroux, Benoit; Bayle, Pierre-Alain; Favier, Alain; Cadet, Jean; Ravanat, Jean-Luc

2007-08-28

357

Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit  

International Nuclear Information System (INIS)

Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (57Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity

1986-01-01

358

An investigation of the structure of the complexes formed between bleomycin and copper(II) and gadolinium(III) paramagnetic ion probes by nuclear magnetic resonance spectroscopy  

International Nuclear Information System (INIS)

Paramagnetic induced spin-lattice proton relaxation enhancements have been used to determine the binding sites of copper(II) and gadolinium(III) bis-nitrilotriacetate to the bleomycin antibiotics. Copper interacts exclusively with the bithiazole moiety and the gadolinium species with the cationic terminal residue. The very similar metal bound conformers are predominantly folded. C.d. spectra of free and bound forms are considerably different, but this does not necessarily imply a difference between free and bound comformers as these might be electrostatic in origin

1979-01-01

359

Concurrent chemotherapy and radiation therapy of selected head and neck squamous cell carcinomas using bleomycin and hydroxyurea: a Southwest Oncology Group study  

International Nuclear Information System (INIS)

Forty-three patients with Stage III or IV squamous cell carcinoma of the head and neck were treated with simultaneous hydroxyurea and bleomycin in four treatment levels and with full-dose radiotherapy. Complete responses ranged from 28 to 50% (P = .47), and complete plus partial responses ranged from 57 to 84% (P = .50), in a total of 33 patients. The primary toxicity was moderate to severe mucositis and minimal leukopenia. Despite good initial response, long-term survival duration was not greater than was that for historical controls

1982-01-01

360

Meiotic and Mitotic Phenotypes Conferred by the blm1-1 Mutation in Saccharomyces cerevisiae and MSH4 Suppression of the Bleomycin Hypersusceptibility  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Abstract: Oxidative damage can lead to a number of diseases, and can be fatal. The blm1-1 mutation of Saccharomyces cerevisiae confers hypersusceptibility to lethal effects of the oxidative, anticancer and antifungal agent, bleomycin. For the current report, additional defects conferred by the mutation in meiosis and mitosis were investigated. The viability of spores produced during meiosis by homozygous normal BLM1/BLM1, heterozygous BLM1/blm1-1, and homozygous mutant blm1-1/blm1-1 diploid s...

Georgia Anyatonwu; Ediberto Garcia; Ajay Pramanik; Marie Powell; Carol Wood Moore

2003-01-01

 
 
 
 
361

Accurate and rapid modeling of iron–bleomycin-induced DNA damage using tethered duplex oligonucleotides and electrospray ionization ion trap mass spectrometric analysis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Bleomycin B2 (BLM) in the presence of iron [Fe(II)] and O2 catalyzes single-stranded (ss) and double-stranded (ds) cleavage of DNA. Electrospray ionization ion trap mass spectrometry was used to monitor these cleavage processes. Two duplex oligonucleotides containing an ethylene oxide tether between both strands were used in this investigation, allowing facile monitoring of all ss and ds cleavage events. A sequence for site-specific binding and cleavage by Fe–BLM was incorporated into each ...

Harsch, Andreas; Marzilli, Lisa A.; Bunt, Richard C.; Stubbe, Joanne; Vouros, Paul

2000-01-01

362

Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit  

Energy Technology Data Exchange (ETDEWEB)

Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (/sup 57/Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity.

Kay, J.S.; Litin, B.S.; Woolfenden, J.M.; Chvapil, M.; Herschler, J.

1986-10-01

363

Interoperation between AODV protocol and AOHR protocol for mobile ad hoc networks  

Science.gov (United States)

Although AOHR protocol has some excellent performance, no actual network utilizes AOHR as routing protocol. It is because that this protocol cannot interoperate with AODV protocol, which is the most famous routing protocol and used all over the world. The cost will be very huge to replace AODV protocol with AOHR protocol for existing networks, so the only feasible method is to modify AOHR protocol to interoperate with AODV as introduced in this paper. The simulation results prove that the modified AOHR protocol can help the existing AODV protocol provide routing service, and the interoperation of these two routing protocols is realized.

Wu, Shaochuan; Wang, Changhong; Zhang, Jiayan

2009-12-01

364

Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast  

International Nuclear Information System (INIS)

The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions

2007-10-01

365

Distinct roles of Ape1 protein in the repair of DNA damage induced by ionizing radiation or bleomycin.  

Science.gov (United States)

Ionizing radiation (IR) and bleomycin (BLM) are used to treat various types of cancers. Both agents generate cytotoxic double strand breaks (DSB) and abasic (apurinic/apyrimidinic (AP)) sites in DNA. The human AP endonuclease Ape1 acts on abasic or 3'-blocking DNA lesions such as those generated by IR or BLM. We examined the effect of siRNA-mediated Ape1 suppression on DNA repair and cellular resistance to IR or BLM in human B-lymphoblastoid TK6 cells and HCT116 colon tumor cells. Partial Ape1 deficiency (?30% of normal levels) sensitized cells more dramatically to BLM than to IR cytotoxicity. In both cases, expression of the unrelated yeast AP endonuclease, Apn1, largely restored resistance. Ape1 deficiency increased DNA AP site accumulation due to IR treatment but reduced the number of DSB. In contrast, for BLM, there were more DSB under Ape1 deficiency, with little change in the accumulation of AP sites. Although the role of Ape1 in generating DSB was greater for IR, the enzyme facilitated removal of AP sites, which may mitigate the cytotoxic effects of IR. In contrast, BLM generates scattered AP sites, and the DSB have 3'-phosphoglycolate termini that require Ape1 processing. These DSB persist under Ape1 deficiency. Apoptosis induced by BLM (but not by IR) under Ape1 deficiency was partially p53-dependent, more dramatically in TK6 than HCT116 cells. Thus, Ape1 suppression or inhibition may be a more efficacious adjuvant for BLM than for IR cancer therapy, particularly for tumors with a functional p53 pathway. PMID:21081487

Fung, Hua; Demple, Bruce

2011-02-18

366

Analysis of spontaneous and bleomycin-induced chromosome damage in peripheral lymphocytes of long-haul aircrew members from Argentina  

Energy Technology Data Exchange (ETDEWEB)

Spontaneous and bleomycin (BLM)-induced chromosomal aberrations in G0 and G2 stages of the cell cycle have been analyzed in peripheral lymphocytes of 21 long-haul aircrew members from Argentina in order to assess BLM-induced clastogenesis as a first approach to determine the DNA repair capacity and thereby the susceptibility to environmental cancers in aircrew. The possibility that occupational exposure of flight personnel to cosmic radiation can induce an adaptive response in their peripheral lymphocytes that can be detected by a subsequent in vitro treatment with BLM was also investigated. For comparison, aberrations were also scored in the lymphocytes of 15 healthy volunteers matched by age, health, sex, drinking and smoking habits to the flight personnel group. Aircrew exhibited a higher frequency of spontaneous dicentrics and ring chromosomes than the control population (p < 0.05). BLM sensitivity test showed that aircrew and controls are equally sensitive to BLM G2 clastogenic effects, since both groups exhibited a similar frequency of chromatid breaks per cell (p > 0.05). However, the aircrew sampled population was almost two times more sensitive to BLM G0 clastogenic effects than controls (p < 0.05). Therefore, our data suggest that chronic exposure of aircrew to cosmic radiation increases the in vitro chromosomal sensitivity of their peripheral lymphocytes to BLM (at least in the G0 stage of the cell cycle), and that occupational exposure of flight personnel to cosmic radiation does not induce an adaptive response to this radiomimetic compound. Our results justify further studies aimed at determine if those aircrew members hypersensitive to BLM are more prone to develop environmental cancer than BLM-insensitive individuals.

Bolzan, Alejandro D. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina)], E-mail: abolzan@imbice.org.ar; Bianchi, Martha S. [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Miembro de la Carrera del Investigador Cientifico del CONICET (Argentina); Gimenez, Esteban M.; Flaque, Maria C. Diaz [Laboratorio de Citogenetica y Mutagenesis, Instituto Multidisciplinario de Biologia Celular (IMBICE), C.C. 403, 1900 La Plata (Argentina); Ciancio, Vicente R. [Universidad Nacional de La Plata, Facultad de Ciencias Medicas, 120 y 60, 1900 La Plata (Argentina)

2008-03-01

367

Chromatin condensation and differential sensitivity of mammalian and insect cells to DNA strand breaks induced by bleomycin  

International Nuclear Information System (INIS)

Bleomycin (BLM) induces DNA damage in living cells. In this report we analyzed the role of chromatin compactness in the differential response of mosquito (ATC-15) and mammalian (CHO) cells to DNA strand breaks induced by BLM. We used cells unexposed and exposed to sodium butyrate (NaB), which induces chromatin decondensation. By nucleoid sedimentation assay and digestions of nuclei with DNAse I, untreated mosquito cells (no BLM; no NaB) were shown to have more chromatin condensation than untreated CHO cells. By alkaline unwinding ATC-15 cells treated with NaB showed more BLM-induced DNA strand breaks than NaB-untreated CHO cells. The time-course of BLM-induced DNA damage to nuclear DNA was similar for NaB-untreated mammalian and insect cells, but with mosquito cells showing less DNA strand breaks, both at physiological temperatures and at 4 oC. However, when DNA repair was inhibited by low temperatures and chromatin was decondensed by NaB treatments, differences in BLM-induced DNA damage between these cells lines were no longer observed. In both cell lines, NaB did not affect BLM action on cell growth and viability. On the other hand, the low sensitivity of ATC-15 cells to BLM was reflected in their better growth efficiency. These cells exhibited a satisfactory growth at BLM doses that produced a permanent arrest of growth in CHO cells. The data suggest that mosquito cells might have linker DNAs shorter than those of mammalian cells, which would result in the observed both greater chromatin condensation and greater resistance to DNA damage induced by BLM as compared to CHO cells

2006-08-30

368

Study on combined effects of radiation and bleomycin on carcinoma of tongue iduced by DMBA in hamster  

International Nuclear Information System (INIS)

Carcinoma of the tongue (Mostly squamous cell carcinoma) was induced in hamsters by 9,10-dimethyl-1, 2-benzanthracene (DMBA). The amount of various kinds of free radicals, which increased due to radioactive radiation and administration of bleomycin (BLM) in tongue and liver tissues, was determined by an electron spin resonance method. The hamsters were separated into seven groups: BLM administration only (group A1), 60Co-?-ray irradiation only (A2), 60Co-?-ray irradiation 30 min after BLM administration (A3), BLM administration 30 min after 60Co-?-ray irradiation (A4), 60Co-?-ray irradiation 24 h after BLM administration (A5), BLM administration 24 h after 60Co-?-ray irradiation (A6), and the control (A7). Mean free radicals in the groups were compared, using samples fixed 5 min after treatment. The ratio of mean free radicals of carcinoma of the tongue were 2.6, 2.9, 3.7, 3.9, 3.0, 3.2, and 1 in A1, A2, A3, A4, A5, A6, and A7. The ratio of mean free radicals of the liver under the same condition were 1.5, 1.6, 3.3, 3.8, 2.2, 2.6, and 1. A combination of BLM and radioactive radiation increased the amount of free radicals in carcinoma of the tongue and in the liver. Especially BLM administration 30 min after 60Co-?-ray irradiation showed a synergistic effect. Judging from the amount of free radicals determined, the effect of radioactive irradiation increased when combined with BLM administration. BLM was most effective when it was administered 5 min after radioactive irradiation. (Tsunoda, M.)

1979-01-01

369

Modulation of the genotoxicity of bleomycin by amines through noncovalent DNA interactions and alteration of physiological conditions in yeast  

Energy Technology Data Exchange (ETDEWEB)

The effects of amines on the induction of mitotic gene conversion by bleomycin (BLM) were studied at the trp5 locus in Saccharomyces cerevisiae strain D7. BLM induces double-strand breaks in DNA and is a potent recombinagen in this assay. The polyamine spermidine causes concentration-dependent protection against the genotoxicity of BLM, reducing the convertant frequency by over 90% under the most protective conditions. Spermine, diethylenetriamine, ethylenediamine, putrescine, and ethylamine were also antigenotoxic in combined treatments with BLM. There was a general correspondence between the protective effect and the number of amino groups, suggesting that more strongly cationic amines tend to be stronger antirecombinagens. Electrostatic association of the amines with DNA probably hinders BLM access to the 4' position of deoxyribose where it generates a free radical. Other amines interact with BLM differently from these unbranched aliphatic amines. The aminothiol cysteamine inhibits the genotoxicity of BLM under hypoxic conditions but increases it under euoxic conditions. In contrast, pargyline potentiates the genotoxicity of BLM under hypoxic conditions but not under euoxic conditions. The antirecombinagenic effect of cysteamine apparently involves DNA binding and depletion of oxygen needed for BLM activity, whereas its potentiation of BLM entails its serving as an electron source for the activation of BLM. Pargyline may enhance BLM indirectly by preventing the depletion of oxygen by monoamine and polyamine oxidase. The planar 9-aminoacridine weakly induces gene conversion in strain D7, but it is strongly synergistic with BLM. Enhancement of BLM activity by this compound and by the related nitroacridine Entozon is apparently mediated by intercalation of the acridine ring system into DNA. Thus, the influence of amines on the genotoxicity of BLM in yeast encompasses antigenotoxic, potentiating, and synergistic interactions. The underlying mechanisms involve noncovalent association with DNA, altered BLM access to DNA, and modulation of physiological conditions.

Hoffmann, George R. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)], E-mail: ghoffmann@holycross.edu; Gessner, Gabrielle S.; Hughes, Jennifer F.; Ronan, Matthew V.; Sylvia, Katelyn E.; Willett, Christine J. [Department of Biology, College of the Holy Cross, One College Street, Worcester, MA 01610-2395 (United States)

2007-10-01

370

Protocols using Anonymous Connections: Mobile Applications.  

Science.gov (United States)

This paper describes security protocols that use anonymous channels as primitive, much in the way that key distribution protocols take encryption as primitive. This abstraction allows us to focus on high level anonymity goals of these protocols much as ab...

M. G. Reed P. F. Syverson D. M. Goldschlag

1997-01-01

371

Protocol Development — Guidelines for Preparing Pharmaceutical Sections  

Science.gov (United States)

Skip to Content Home | Investigator Resources | Protocol Development | Initiatives/Programs/Collaborations | Links to More Resources | Funding Opportunities | About CTEP Home | Sitemap | Contact CTEP Search this site Protocol Development Protocol

372

A Toolbox for Protocol Analysis  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This B.Sc. thesis evolves around protocol analysis. Communication protocols are a very important and a highly researched area of computer science and the importance has increased rapidly due to the growing communication. It is therefore imperative that the communication is done in a safe and secure way. One way of analysing and controlling a protocol is by using the LySa tool. The concrete case that the thesis works through is the development of a frontend editor to support the LySa tool. The...

Singla, Ketan; Christensen, Lasse

2008-01-01

373

Analysis of Two Types Deniable Authentication Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available Deniability enables protocol participants to deny their involvement after they have taken part in a particular protocol run. In this paper, we present the security analysis of a class of interactive deniable authentication protocols and a noninteractive one. For interactive protocols, we focus on a serial of pairings based protocols proposed by Chou et al and repaired by Lim et al. We point out that their repaired protocols are still not secure under Key Compromise Impersonation (KCI attack and give it an improvement. For noninteractive protocols, we point out that most current noninteractive deniable authentication protocols are not secure under KCI attack.

Haibo Tian

2009-11-01

374

New waste protocol for biomethane  

Biomethane is produced from biogass generated from landfills and anaerobic digestion. We are looking at the standards it must meet to allow it to be used without waste management controls. Related Searches: biomethane protocol biogas

375

Invertible Extractors and Wiretap Protocols  

CERN Document Server

A wiretap protocol is a pair of randomized encoding and decoding functions such that knowledge of a bounded fraction of the encoding of a message reveals essentially no information about the message, while knowledge of the entire encoding reveals the message using the decoder. In this paper we study the notion of efficiently invertible extractors and show that a wiretap protocol can be constructed from such an extractor. We will then construct invertible extractors for symbol-fixing, affine, and general sources and apply them to create wiretap protocols with asymptotically optimal trade-offs between their rate (ratio of the length of the message versus its encoding) and resilience (ratio of the observed positions of the encoding and the length of the encoding). We will then apply our results to create wiretap protocols for challenging communication problems, such as active intruders who change portions of the encoding, network coding, and intruders observing arbitrary boolean functions of the encoding.

Cheraghchi, Mahdi; Shokrollahi, Amin

2009-01-01

376

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

In addition to the targeted mutation in the Tgfb1 gene, this strain carries a targeted insertion of the Neo cassette in the Rag2 gene. This genotyping protocol will distinguish between wt, heterozygote, and homozygote animals carrying the Rag2 mutation. This protocol should be used in addition to the allele specific PCR for the Tgfb1 mutant allele to select double mutant animals.

377

On the Mutability of Protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

The task of developing a framework for which agents can communicate reliably and flexibly in open systems is not trivial. This thesis addresses the dichotomy between reliable communication and facilitation of the autonomy of agents to create more flexible and emergent interactions. By the introduction of adaptations to a distributed protocol language, agents benefit from the ability to communicate interaction protocols to elucidate the social norms (thus creating more reliable ...

Mcginnis, Jarred P.

2006-01-01

378

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

B6.129-Msh6tm1Rak/Nci PCR Protocol Strain: B6.129-Msh6tm1Rak/Nci Strain Code: 01XA4 Protocol Number: 1 Introductory Comment: Primers:  M010 :   5'-TGG AAG GAT TGG AGc TAc GG -3'  M011 :   5'-TTA ccT ccT ccA cTG AcG TG -3'  M012 :   5'-cAA Gcc ccT

379

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

C57BL/6-Tg(Wap-rtTA-cre)10Whl/Nci PCR Protocol Strain: C57BL/6-Tg(Wap-rtTA-cre)10Whl/Nci Strain Code: 01XD9 Protocol Number: 2 Introductory Comment: Primers:  R009 :   5'-AGG GAA AcA ccT AcT AcT GA -3'  R010 :   5'-ATT ccA AGG GcA TcG GTA -3' Product

380

Kyoto Protocol one step closer  

Science.gov (United States)

The European Union (EU) could soon decide to ratify the Kyoto Protocol on climate change, following a 4 March meeting of the European Commissions environment council to approve the treaty.European Commission President Romani Prodi said the council's move enables the 15 EU member states to take the steps toward simultaneous ratification together with the commission before 1 June."I urge our partners both in the developed and in the developing countries to also ratify the Kyoto Protocol soon," he said.

Showstack, Randy

 
 
 
 
381

Verifying authentication protocols in CSP  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This paper presents a general approach for analysis and verification of authentication properties using the theory of Communicating Sequential Processes (CSP). The paper aims to develop a specific theory appropriate to the analysis of authentication protocols, built on top of the general CSP semantic framework. This approach aims to combine the ability to express such protocols in a natural and precise way with the ability to reason formally about the properties they exhibit. The the...

Schneider, Steve A.

1998-01-01

382

Analysis of the dose-response relationships of chromosomal aberrations after irradiation and bleomycin exposure of different human lymphocyte fractions in vitro  

International Nuclear Information System (INIS)

Cytogenetic analyses could be carried out on whole blood and pure T-cell cultures and also on cells of the 'buffy-coat'. In pure B-cell cultures even after 96 hours no mitogenic stimulation could be achieved. Parameters of radiosensitivity and bleomycin sensitivity were dicentric chromosomes, for which the dose-response relationships were calculated. Chromosomal investigations on the 'buffy-coat' cells did not provide indications referring to a varying radiosensitivity compared to whole blood cultures. In pure T-cell cultures T-lymphocytes, which had been separated after whole blood irradiation exposure, showed lower aberration rates than lymphocytes, which had been cultured after whole blood irradiation without previous separation. In the case of bleomycin exposure the treatment of previously separated leucocytes and T-lymphocytes respectively, led to lower aberration rates than the treatment before separation. Therefore it is apparently not necessary for a cytogenetic dosimetry or mutagenicity to depart from the whole blood culture method. (orig./MG)

1979-01-01

383

A comparison of cobalt (57Co) bleomycin scanning and contrast-enhanced CT scanning for assessment of the mediastinum in lung cancer  

International Nuclear Information System (INIS)

Sixty patients with histologically proven lung cancer who had been accepted for mediastinoscopy or thoracotomy were prospectively entered into a study to evaluate computed tomographic (CT) scanning, 57Co-bleomycin scanning, and barium swallow in preoperative assessment of mediastinal lymph node metastasis. Fifty-six patients had thoracotomy at which all accessible lymph nodes were sampled. Twenty-four patients were found to have mediastinal tumor on histologic analysis of the resected mediastinal lymph nodes. Neither 57Co-bleomycin scanning nor barium swallow were clinically useful, with sensitivities of 21 percent and 11 percent respectively, whereas CT scanning was helpful. However, there was no clear cutoff point of node size to optimize sensitivity and specificity for CT scanning. When nodes greater than or equal to 15 mm were taken to indicate likely malignancy, the sensitivity was 58 percent and the specificity was 87 percent and when greater than or equal to 10 mm was used the sensitivity was 80 percent but the specificity was only 55 percent. There was no clear relationship between the size of the largest resected lymph node in each patient and the presence of malignant lymph nodes. Only 42 percent of patients with resected nodes greater than or equal to 2 cm had histologic evidence of metastases. We conclude that CT scanning should be used to indicate the presence and site of mediastinal lymph nodes, which, when visualized, should always be sampled and histologically examined prior to resection of primary tumor

1990-01-01

384

Secure E-payment Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available The vast spreading of information in the last decade has led to greatdevelopment in e-commerce. For instance, e-trade and e-bank are two mainInternet services that implement e-transaction from anyplace in the world. Thishelps merchant and bank to ease the financial transaction process and to giveuser friendly services at any time. However, the cost of workers andcommunications falls down considerably while the cost of trusted authority andprotecting information is increased. E-payment is now one of the most centralresearch areas in e-commerce, mainly regarding online and offline paymentscenarios. In this paper, we will discuss an important e-payment protocol namelyKim and Lee scheme examine its advantages and delimitations, whichencourages the author to develop more efficient scheme that keeping allcharacteristics intact without concession of the security robustness of theprotocol. The suggest protocol employs the idea of public key encryption schemeusing the thought of hash chain. We will compare the proposed protocol with Kimand Lee protocol and demonstrate that the proposed protocol offers moresecurity and efficiency, which makes the protocol workable for real worldservices.

Sattar J Aboud

2009-11-01

385

Recent Advances in Population Protocols  

Science.gov (United States)

The population protocol model (PP) proposed by Angluin et al. [2] describes sensor networks consisting of passively mobile finite-state agents. The agents sense their environment and communicate in pairs to carry out some computation on the sensed values. The mediated population protocol model (MPP) [13] extended the PP model by communication links equipped with a constant size buffer. The MPP model was proved in [13] to be stronger than the PP model. However, its most important contribution is that it provides us with the ability to devise optimizing protocols, approximation protocols and protocols that decide properties of the communication graph on which they run. The latter case, suggests a simplified model, the GDM model, that was formally defined and studied in [11]. GDM is a special case of MPP that captures MPP’s ability to decide properties of the communication graph. Here we survey recent advances in the area initiated by the proposal of the PP model and at the same time we provide new protocols, novel ideas and results.

Chatzigiannakis, Ioannis; Michail, Othon; Spirakis, Paul G.

386

Monoclonal antibodies technology. Protocols  

International Nuclear Information System (INIS)

Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 ?g/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x10"7 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x10"7 spleen cells to 1x10"6 myeloma cells (ratio 10:1). Centrifuge the mixture of cells at 300g for 10 minutes. While the cells are centrifuging, set aside 30 ml of serum-free RPMI 1640 in another 50-ml tube. Prepare the 50% PEG and place the timer in the hood. 6. Remove all the supernatant from the cell pellet. Overlay the pellet of cells with 0.5 ml of 50% PEG with a Pasteur pipet during 1 minute. Then add 5 ml of serum-free RPMI 1640 during 3 minutes. At the end of 3 minutes, add during a minute 15 ml of the same medium. 7. Centrifuge at 250g for 10 minutes. Gently resuspend the fused cells at a concentration of 5 x10"4 cells/ml, in a RPMI medium containing serum at 20%, HAT (selective growth) and antibiotics. 8. Distribute the cell suspension into 96-well-flat-bottom-tissue-culture plates add 0.2 ml per well. Incubate the plates at 37 deg. C in 5% CO_2. Three to 4 days in HAT medium is sufficient for arresting the proliferation of unfused myeloma cells. Screening and establishing a Hybridorna line. The screening could be perform using different immunoassay alternatives (ELISA, RIA, etc). The principal requisite is have been developed a reproducible method before to make the fusion. These method could be improve using the serum of mice immunized as sample. Approximately 1 week after the fusion, colonies of hybrid cells will be ready to screen. During the screening, samples of tissue culture media are removed from wells that have growing hybridomas and are tested for the presence of the desired antibodies. Successful fusions will produce between 2000 and 5000 hybridomas colonies. Depending on the fusion, individual wells will become ready to screening over 2 to 6 day period. Typically, the first wells could be ready to screen in day 7 or 8, and most of the wells will need to be screened within the next 4 or 5 days. When you detected a possible positive clone, you could transfer hybrids of interest to 24-plates adding 1 ml of HAT medium (RPMI 1640) supplemented with serum at 20%. Cryopreserve each culture of cells when they have reached at least 3/4 confluency, 2 ampules/cell culture. Save the supernatants for further studie

1997-12-09

387

Elliptic Curve Cryptography Based Wireless Authentication Protocol  

Directory of Open Access Journals (Sweden)

Full Text Available Recently, Aydos et al. proposed an ECC-based wireless authentication protocol. Because their protocol is based on ECC, the protocol has significant advantage including lower computational burden, lower communication bandwidth and storage requirements. However, Mangipudi et al showed that the protocol is vulnerable to the man-in-the-middle attack from the attacker within the system and proposed a user authentication protocol to prevent the attack. This paper further shows that Aydos et al.'s protocol is vulnerable to man-in-the-middle attack from any attacker not restricted on the inside attacker. Then, a forging certificate attack on Mangipudi et al's protocol is presented. Next, the reasons that Aydos et al's protocol and Mangipudi et al's protocol suffer the attacks are analyzed. Finally, we propose a novel ECC-based wireless authentication protocol and analyze the security of our protocol.

Liu Yongliang

2007-11-01

388

Tissue uptakes of 67Ga-bleomycin and carrier free 67Ga in fibrosarcoma-bearing mice  

Directory of Open Access Journals (Sweden)

Full Text Available 67Gallium-bleomycin complex (67Ga-BLM was prepared using Thakour method. Radio-thin-layer-chromatography of prepared complex showed A2 and B2 radiopeaks with Rf at 0.7 and 0.4 respectively with a purity of above % 95. Tissue uptake of 67Ga-BLM and 67GaCl3 in twelve tissues including tumor, blood, liver, lung, spleen, muscle, skin, heart, kidney, colon, colon content ,bladder and the total body were counted by well counter at 1, 2, 4, 24 and 48 hours post injection of radiopharmaceuticals. Uptakes of tissues are expressed as percent injected dose per gram of tissue. The clearance rate of 67Ga-BLM was 1.75-1.95 times faster than 67GaCl3 at all time intervals. Bladder uptakes of 67Ga-BLM were highest among twelve tissues at 1,2 and 4 hours after injection, then falling rapidly after 24 and 48 hours. Blood uptake of 67Ga-BLM was lower than 67GaCl3 in all time intervals. Colon content uptake of 67Ga-BLM was highest among twelve tissues at 2 and 4 hours post injection. Tumor to tissue activity ratios were also calculated, showing an increase of tumor to blood and muscle ratios. Tumor to blood ratio increased from 0.3 at 1 hour to 5.3 at 48 hours. Activity ratio of muscle increased from 0.5 at 1 hour to 5.5 at 48 hours. Whole body counting of animals showed that effective half lives of 67Ga-BLM and 67GaCl3 were about 1 and 15 hours respectively, which renders faster excretion of 67Ga-BLM complex. Biodistribution data clearly indicates that prepared complex in comparison with carrier free 67Ga (67GaCl3 has two main advantages: 1 high tumor to soft tissue uptake ratio that make it suitable for tumor imaging, 2 faster excretion specially at first three hours post injection. In addition complex is stable in vitro and in vivo.

H. Rajabi I. Neshar- Asli "

2004-08-01

389

Embedded Network Protocols for Mobile Devices  

Science.gov (United States)

Embedded networks for chip-to-chip networks are emerging as communication infrastructure in mobile devices. We present three novel embedded network protocols: a sliding window protocol, a protocol for opening and closing connections, and a bandwidth reservation protocol. The design of these protocols is tailored to the low power and low cost requirements of mobile devices. The model checker SPIN played an important role in the design and analysis of these protocols. Large instances of the protocols could be analyzed successfully using the distributed model checker DiVinE.

Galataki, Despo; Radulescu, Andrei; Verstoep, Kees; Fokkink, Wan

390

Superselection rules and quantum protocols  

International Nuclear Information System (INIS)

We show that superselection rules do not enhance the information-theoretic security of quantum cryptographic protocols. Our analysis employs two quite different methods. The first method uses the concept of a reference system--in a world subject to a superselection rule, unrestricted operations can be simulated by parties who share access to a reference system with suitable properties. By this method, we prove that if an n-party protocol is secure in a world subject to a superselection rule, then the security is maintained even if the superselection rule is relaxed. However, the proof applies only to a limited class of superselection rules, those in which the superselection sectors are labeled by unitary irreducible representations of a compact symmetry group. The second method uses the concept of the format of a message sent between parties--by verifying the format, the recipient of a message can check whether the message could have been sent by a party who performed charge-conserving operations. By this method, we prove that protocols subject to general superselection rules (including those pertaining to non-Abelian anyons in two dimensions) are no more secure than protocols in the unrestricted world. However, the proof applies only to two-party protocols. Our results show in particular that, if no assumptions are made about the computational power of the cheater, then secure quantum bit commitment and strong quantum coin flipping with arbitrarily small bias are impossible in a world subject to superselection rules

2004-05-01

391

Security Issues of Routing Protocols in MANETs  

Digital Repository Infrastructure Vision for European Research (DRIVER)

There are a number of routing protocols developed by researchers. Due to the nature of ad hoc networks, secure routing is an important area of research in developing secure routing protocols. Although researchers have proposed several secure routing protocols, their resistance towards various types of security attacks and efficiency are primary points of concern in implementing these protocols. This paper presents some of the available secure routing protocols and most common attack ...

Kaushal Gandhi; Rajneesh Narula; Sumeer Khullar; Anish Arora

2012-01-01

392

Performance Bounds for Bidirectional Coded Cooperation Protocols  

Digital Repository Infrastructure Vision for European Research (DRIVER)

In coded bidirectional cooperation, two nodes wish to exchange messages over a shared half-duplex channel with the help of a relay. In this correspondence, we derive performance bounds for this problem for each of three decode-and-forward protocols. The first protocol is a two phase protocol where both users simultaneously transmit during the first phase and the relay alone transmits during the second. In this protocol, our bounds are tight. The second protocol considers sequential transmissi...

Mitran, Patrick; Kim, Sang Joon; Tarokh, Vahid

2008-01-01

393

Meiotic and Mitotic Phenotypes Conferred by the blm1-1 Mutation in Saccharomyces cerevisiae and MSH4 Suppression of the Bleomycin Hypersusceptibility  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract: Oxidative damage can lead to a number of diseases, and can be fatal. The blm1-1 mutation of Saccharomyces cerevisiae confers hypersusceptibility to lethal effects of the oxidative, anticancer and antifungal agent, bleomycin. For the current report, additional defects conferred by the mutation in meiosis and mitosis were investigated. The viability of spores produced during meiosis by homozygous normal BLM1/BLM1, heterozygous BLM1/blm1-1, and homozygous mutant blm1-1/blm1-1 diploid strains was studied and compared. Approximately 88% of the tetrads derived from homozygous blm1-1/blm1-1 mutant diploid cells only produced one or two viable spores. In contrast, just one tetrad among all BLM1/BLM1 and BLM1/blm1-1 tetrads only produced one or two viable spores. Rather, 94% of BLM1/BLM1 tetrads and 100% of BLM1/blm1-1 tetrads produced asci with four or three viable spores. Thus, at least one copy of the BLM1 gene is essential for the production of four viable spores after meiosis. During mitotic growth, mutant blm1-1 strains grew at reduced rates and produced cells with high frequencies of unusual morphologies compared to wild-type strains. These results indicated BLM1 is also essential for normal mitotic growth. We also investigated the suppression by the MSH4 gene, a meiosis-specific MutS homolog, of the bleomycin hypersusceptibility of blm1-1 mutant cells, and the relationship of MSH4 to BLM1. We screened a genomic library, and isolated the MSH4 gene on the basis of its ability to suppress lethal effects of bleomycin in blm1-1 cells. However, genetic mapping studies indicated that BLM1 and MSH4 are not the same gene. The possibility that chromosomal nondisjunction could be the basis for the inability of blm1-1/blm1-1 mutant cells to produce four viable spores after meiosis is discussed.

Carol Wood Moore

2003-01-01

394

Therapeutic potential of human-induced pluripotent stem cell-derived endothelial cells in a bleomycin-induced scleroderma mouse model.  

Science.gov (United States)

Vascular injury and destruction of endothelial cells (ECs) are the early events in scleroderma (SSc) patients. This study aims to investigate the therapeutic potential of human-induced pluripotent stem cell-derived ECs (hiPSC-ECs) to treat SSc. We have assessed the functional differentiation of hiPSC-ECs and compared them with human embryonic stem cell-derived ECs (hESC-ECs) by a variety of in vitro experimental approaches. Additionally, we evaluated the therapeutic potential of hiPSC-ECs in a bleomycin-induced SSc mouse model. Our results demonstrated that hiPSC-ECs and hESC-ECs showed similar maximum expressions of FLK1 (early EC marker) at day five during differentiation. After sorting and culturing, the FLK1-positive cells exhibited spindle and subsequent endothelial cobblestone morphology in EGM2 medium. The hESC-ECs and hiPSC-ECs also expressed late EC markers CD31 (68% and 75%), CD144 (50% and 61%), CD146 (46% and 61%), and DiI-labeled acetylated low-density lipoprotein (DiI-ac-LDL) uptake (55% and 63%), respectively. They additionally formed capillary-like structures on Matrigel. Analyses of the transplantation of sorted CD31-positive hiPSC-ECs into the bleomycin-induced SSc mouse model demonstrated that these cells participate in recovery of the damaged vessels. There was a reduction in collagen content; the number of total and degranulated mast cells returned to their normal state, and bleomycin-induced wounds as well as skin fibrosis improved four weeks after transplantation of hiPSC-ECs. Our findings have shown that the differentiation process from hESCs and hiPSCs to vascular cell components is similar. Additionally, this is the first study to determine the therapeutic potential of vascular cells from hiPSCs in the treatment of an SSc model. In the future, with further validation, these may be used as an appropriate source for the treatment of SSc patients. PMID:23396195

Azhdari, Manizheh; Baghaban-Eslaminejad, Mohamadreza; Baharvand, Hossein; Aghdami, Nasser

2013-05-01

395

Influence of Feixian Formula on serum transforming growth factor-?1 and platelet-derived growth factor in rats with bleomycin-induced pulmonary fibrosis  

Directory of Open Access Journals (Sweden)

Full Text Available Objective: To observe the effects of Feixian Formula, a compound traditional Chinese herbal medicine for treating pulmonary fibrosis, on bleomycin-induced pulmonary fibrosis in rats, and its influence on serum transforming growth factor-?1 (TGF-?1 and platelet-derived growth factor (PDGF.Methods: Seventy-two male Wistar rats were infused with bleomycin (1 mg/kg through tracheal intubation to induce pulmonary fibrosis, and they were randomly divided into untreated group (n=24, prednisone-treated group (n=24 and Feixian Formula-treated group (n=24. Fifteen male Wistar rats of the sham-operated group were infused with equivalent normal saline. Twenty-four hours after operation, prednisone (5 mg/kg and Feixian Formula (1.25 g/kg were given to the prednisone-treated group and Feixian Formula-treated group respectively by intragastric administration once a day. Equivalent saline was administered to rats of the untreated group and sham-operated group. On the 14th, 28th and 45th day, 5 rats in the sham-operated group and 8 rats in each of the other three groups were dissected to observe pathologic changes of the lung tissues, and the levels of serum TGF-?1 and PDGF were determined by enzyme-linked immunosorbent assay.Results: At the 45th day, the degree of pulmonary interstitial fibrosis was lesser in rats of the Feixian Formula-treated group as compared with those of the untreated group and prednisone-treated group. The levels of serum TGF-?1 and PDGF were increased, and were significantly higher than those of the sham-operated group, especially on the 45th day (P0.05, and there was no significant difference between the prednisone-treated group and the Feixian Formula-treated group (P>0.05. PDGF in the Feixian Formula-treated group reached the highest level on the 14th day, significantly higher than those of the other three groups (P<0.01. Then it decreased, and was close to that of the sham-operated group on the 45th day (P=0.792. The levels of PDGF in untreated group and prednisone-treated group were increased depending on time, and were obviously higher than that of the sham-operated group on the 45th day (P<0.01. Conclusion: Feixian Formula can relieve bleomycin-induced pulmonary fibrosis in rats, and the mechanism of its action may be related to down-regulating serum PDGF.

Wei ZHANG

2008-06-01

396

Current protocols in human genetics  

Energy Technology Data Exchange (ETDEWEB)

Much of the experience accumulated from using the positional cloning approach for identifying new disease genes has been brought together in this single volume. This book is a well-organized and comprehensive collection of more than 150 protocols. Although comprehensive, this volume is not complete. The book was designed to be a companion book to the popular `Current Protocols of Molecular Biology`; thus many of the basic techniques are referred to rather than explained. Overall, this book is an excellent research and teaching tool. Genome researchers will find this volume worth its weight.

Dracopoli, N.C.; Haines, J.L.; Korf, B.R. [eds.] [and others

1994-12-31

397

Optimization of Collection Tree Protocol  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Collection tree protocol is a tree based protocol which is mainly used for aggregation. It is minimum cost routing tree which selects the path having minimum cost routing gradient. It will generate one or more trees to root which is called base station. When any node has data it sends data up the tree which is forwarded to root.CTP will provide link quality estimation among nearby neighbours. It will indicate number of transmissions from a node to send a packet to destination and whose acknow...

2013-01-01

398

NCI Mouse Repository- Protocol Information  

Science.gov (United States)

C3H/He-Tg(RIP1-Tag5)5Dh/Nci PCR Protocol Strain: C3H/He-Tg(RIP1-Tag5)5Dh/Nci Strain Code: 01XD4 Protocol Number: 1 Introductory Comment: Primers:  T018 :   5'-GGA cAA Acc AcA AcT AGA ATG cAG -3'  T020 :   5'-cAc cGG AGA ATG GGA AGc cGA A -3'  T019

399

Bundle Security Protocol for ION  

Science.gov (United States)

This software implements bundle authentication, conforming to the Delay-Tolerant Networking (DTN) Internet Draft on Bundle Security Protocol (BSP), for the Interplanetary Overlay Network (ION) implementation of DTN. This is the only implementation of BSP that is integrated with ION.

Burleigh, Scott C.; Birrane, Edward J.; Krupiarz, Christopher

2011-01-01

400

Key elements of Kyoto Protocol  

Energy Technology Data Exchange (ETDEWEB)

A Kyoto Protocol was adopted on December 11, 1997 at the Third Conference of the Parties to the Framework Convention on Climate Change. The agreement on the legally binding protocol called for industrialized countries to reduce their collective emissions of six greenhouse gases to 5.2 per cent below 1990 emission levels between the years 2008 and 2012. The 5.2 per cent reduction in total developed country emissions will be realized through targets for national reductions ranging from 8 per cent to 10 per cent. Canada`s binding target is a reduction of 6 per cent. The six major greenhouses gases are carbon dioxide, methane, nitrous oxide, hydrofluorocarbons, perfluorocarbons and sulphur hexafluoride. The right for parties to trade emissions reductions credits to meet their commitments was included in the protocol. This mechanism was seen as a good way to share the burden of global emissions while keeping costs down. It was recognized that the response to the Kyoto Protocol will require the participation of all levels of government, the public sector, the private sector, and non-government organizations. The agreement permits national flexibility on the means to implement commitments, meaning that countries retain full flexibility to pursue those policies and measures which, while adequate to achieve commitments are, at the same time, most appropriate for specific national circumstances.

Irish, J. [Department of Foreign Affairs and International Trade, Ottawa, ON (Canada)

1998-09-01

 
 
 
 
401

Instantiating and monitoring treatment protocols.  

Digital Repository Infrastructure Vision for European Research (DRIVER)

This paper presents a system for protocol-based treatment planning, plan execution, and execution monitoring. The approach, named SPIN, is developed as a component of the Guardian system. Guardian is an experimental architecture for intelligent patient monitoring and control. The paper describes and illustrates SPIN in a clinical scenario.

Uckun, S.

1994-01-01

402

Superposition Attacks on Cryptographic Protocols  

DEFF Research Database (Denmark)

Attacks on classical cryptographic protocols are usually modeled by allowing an adversary to ask queries from an oracle. Security is then defined by requiring that as long as the queries satisfy some constraint, there is some problem the adversary cannot solve, such as compute a certain piece of information. In this paper, we introduce a fundamentally new model of quantum attacks on classical cryptographic protocols, where the adversary is allowed to ask several classical queries in quantum superposition. This is a strictly stronger attack than the standard one, and we consider the security of several primitives in this model. We show that a secret-sharing scheme that is secure with threshold $t$ in the standard model is secure against superposition attacks if and only if the threshold is lowered to $t/2$. We use this result to give zero-knowledge proofs for all of NP in the common reference string model. While our protocol is classical, it is sound against a cheating unbounded quantum prover and computational zero-knowledge even if the verifier is allowed a superposition attack. Finally, we consider multiparty computation and show that for the most general type of attack, simulation based security is not possible. However, putting a natural constraint on the adversary, we show a non-trivial example of a protocol that can indeed be simulated.

Damgård, Ivan Bjerre; Funder, Jakob Løvstad

2011-01-01

403

Intra-arterial mitomycin C and intravenous bleomycin as induction chemotherapy in advanced head and neck cancer - a phase II study  

International Nuclear Information System (INIS)

Fifty-six patients with previously untreated, unresectable squamous cell carcinomas of the head and neck region were treated with repeated intra-arterial chemotherapy with mitomycin C using a selective or superselective angiographic technique, and bleomycin given i.v., followed by radical radiotherapy. In addition, restricted tumour-reductive surgery was done in 18 of these patients. The response rate (CR + PR) after completion of the integrated treatment was 89%, with 63% of the patients showing CR. The toxicity of this regimen was, however, far from negligible. The median survival for this series of patients with advanced head and neck cancers is 19 months, and 17 are still alive after 16+ - 66+ months. (Auth.)

1986-09-01

404

Effect of vincristine or bleomycin on radiation-induced cell killing of mice spermatogonial stem cells: The importance of sequence and time interval  

Energy Technology Data Exchange (ETDEWEB)

The effect of single doses of vincristine (VCR) or bleomycin (BLM) on mice spermatogonia was investigated, and the influence of either of these drugs on the radiation response of murine spermatogonial stem cells was examined. When assessed by flow cytometry, VCR (1.0 mg/kg) or BLM (100 mg/kg) reduced the survival in the differentiated spermatogonia to 4% and 37% of controls, respectively (p less than 0.05). VCR reduced the stem cells to 79% of controls (p less than 0.05), whereas BLM had no apparent effect on the stem cells (p greater than 0.05). Drugs were administered intraperitoneally up to 28 days before or after local irradiation with 9 Gy. VCR produced significant enhancement of radiation-induced damage to spermatogonial stem cells, which was most prominent when administered 6 or 12 hr after irradiation. BLM administered before irradiation or 1 hr after radiotherapy produced significant enhancement.

Hansen, P.V.; Sorensen, D. (Danish Cancer Society, Aarhus (Denmark))

1991-02-01

405

Successful treatment of multiple basaliomas with bleomycin-based electrochemotherapy: a case series of three patients with Gorlin-Goltz syndrome.  

Science.gov (United States)

Gorlin-Goltz syndrome is a rare multisystemic disease, characterized by numerous basal cell carcinomas. The ideal approach for patients with the syndrome would be a treatment with a high cure rate, minimal scarring, short healing time and mild side-effects. Electrochemo-therapy is a novel therapeutic option that ablates tumours with electrical current and simultaneously administered anticancer drugs. Three patients with Gorlin-Goltz syndrome were treated with electrochemotherapy using intravenous bleomycin. Clinical response was obtained in 98 (99%) of the lesions, 86 (87%) of them showed complete response. In 2 tumours, regression was confirmed with histological examination. Long-term cosmetic results were excellent. We consider electrochemotherapy to be an additional tool in the therapeutic armamentarium for Gorlin-Goltz syndrome, and suggest using it as early as possible in selected patients to avoid disfiguring scarring. PMID:22565566

Kis, Erika; Baltás, Eszter; Kinyó, Agnes; Varga, Erika; Nagy, Nikoletta; Gyulai, Rolland; Kemény, Lajos; Oláh, Judit

2012-11-01

406

Acidente vascular cerebral isquêmico após quimioterapia com cisplatina, etoposide e bleomicina: relato de caso / Ischemic stroke after chemotherapy with cisplatin, etoposide and bleomycin: case report  

Scientific Electronic Library Online (English)

Full Text Available SciELO Brazil | Language: Portuguese Abstract in portuguese Relatamos o caso de um homem de 20 anos, com diagnóstico de tumor de células germinativas, que apresentou acidente vascular cerebral isquêmico durante quimioterapia com cisplatina, etoposide e bleomicina. Os casos relatados na literatura foram revisados, bem como os diferentes mecanismos fisiopatoló [...] gicos implicados na toxicidade vascular deste esquema quimioterápico. Abstract in english A 20-year-old man with a germ cell tumor who experienced an ischemic stroke as a complication of cisplatin/etoposide/bleomycin based chemotherapy is reported. The previously reported cases are reviewed as well as the different physiopathologic mechanisms associated with vascular toxicity of this reg [...] imen.

Adrialdo José, Santos; Suzana Maria Fleury, Malheiros; Lia Raquel Rodrigues, Borges; Carlos, Dzik; Darcio G, Nalli; Alberto Alain, Gabbai.

407

Combined chemotherapy and radiotherapy in diffuse large cell immunoblastic lymphoma: a phase II study of CHOP/bleomycin/methotrexate alternating with ifosfamide/methotrexate/etoposide  

Energy Technology Data Exchange (ETDEWEB)

The clinical outcome of 23 patients with high grade diffuse large cell immunoblastic lymphoma (Working Formulation, category H) treated by an intensive shortened schedule regimen of chemotherapy is described. Alternating cycles of cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisolone, and ifosfamide, etoposide and methotrexate were given over an 18-week (range 16.0-20.8) period. External beam radiotherapy was administered as consolation therapy to sites of original bulky disease in 17 patients. Treatment was well tolerated, though there were two toxic deaths. A 90% response rate was obtained. Sixteen of 18 patients followed for a minimum of 36 months are alive and in complete remission, representing a disease free survival of 69.5%; two further patients are alive following autologous bone marrow transplant. The 3-year disease free survival was 73% ({+-}9%) and the overall 3-year survival 78% ({+-}9%). (author).

Rodriguez, J.M.; Khan, A.A. [Al-Hada Armed Forces Hospital, Al-Taif (Saudi Arabia)

1995-12-01

408

Combined chemotherapy and radiotherapy in diffuse large cell immunoblastic lymphoma: a phase II study of CHOP/bleomycin/methotrexate alternating with ifosfamide/methotrexate/etoposide  

International Nuclear Information System (INIS)

The clinical outcome of 23 patients with high grade diffuse large cell immunoblastic lymphoma (Working Formulation, category H) treated by an intensive shortened schedule regimen of chemotherapy is described. Alternating cycles of cyclophosphamide, doxorubicin, vincristine, bleomycin and prednisolone, and ifosfamide, etoposide and methotrexate were given over an 18-week (range 16.0-20.8) period. External beam radiotherapy was administered as consolation therapy to sites of original bulky disease in 17 patients. Treatment was well tolerated, though there were two toxic deaths. A 90% response rate was obtained. Sixteen of 18 patients followed for a minimum of 36 months are alive and in complete remission, representing a disease free survival of 69.5%; two further patients are alive following autologous bone marrow transplant. The 3-year disease free survival was 73% (±9%) and the overall 3-year survival 78% (±9%). (author)

1995-01-01

409

A Survey of Multicast Routing Protocols  

Directory of Open Access Journals (Sweden)

Full Text Available connected by wireless.A protocol manages group membership and controls the path that multicast data takes over the network. Examples of multicast routing protocols include Protocol Independent Multicast (PIM. There are lots of multicast routing protocols, some works with wired networks while the others with wireless networks, some protocols deals with both wired and wireless networks. But applying this concept in Mobile Ad Hoc networks (Manets is a big challenge. The main aim of this paper is to explore the performance characteristics of multicast protocols

R.Janakavi,V. Keerthana, S. Ramya, S. Gayathri Devi