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 pulmonares, hepáticas e retroperitoneais. Após orquiectomia radical, o paciente começou a receber quimioterapia de acordo com o protocolo BEP (sem profilaxia rotineira p (more) ara 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 prophyl (more) axis 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.

Testis cancer is rare, but it is the commonest cause of malignancy in young men. Painless scrotal masses must be investigated with ultrasound imaging and tumour marker assay before being treated urgently with radical inguinal orchidectomy. Disease localized to the scrotum is curable with surgery alone in most cases, but high-risk features in clinical stage 1 disease predict failure in a significant proportion. Such cases need close surveillance or adjuvant intervention therapy following primary surgery. More advanced disease (clinical stage 2 or greater) requires treatment with combination platinum-based chemotherapy, usually with the cytotoxic agents, bleomycin, etoposide and cisplatinum (BEP). Post-chemotherapy tumour masses are resected surgically when this is possible. The disease is s...

Objective: To analyze the role of surgical staging and adjuvant chemotherapy in patients with adult type granulosa cell tumor (GCT) of the ovary. Methods: Patients were divided into those with early-stage (stages I-II, n=93) and advanced-stage (stages III-IV, n=13) GCT and analyzed separately in this retrospective study. Results: Of the 93 patients with early-stage GCT, 30 were completely staged and 25 underwent lymph node dissection. After surgery, 17 patients received adjuvant chemotherapy with bleomycin/etoposide/cisplatin (BEP). None had lymph node metastasis. Completely staged patients had no recurrence or deaths. However, recurrences were observed in 9 of 63 patients (14.3%) who did not undergo complete staging, with four (6.3%) dying due to disease. The 5-year disease-free survival ...

Three groups of 15 male guinea pigs each were treated with Bleomycin, Bleomycin and ascorbic acid or saline and ascorbic acid. Bleomycin and saline were administered every four days for six weeks by intracardiac injection, while ascorbic acid was injected...

Granulosa cell tumors (GCTs) of the ovary account for 2 to 5 of ovarian malignancies. We present two patients with malignant ovarian adult GCT. In one patient, a combination of bleomycin, etoposide, and cisplatin was effective after initial surgery for malignant GCT. In the other, an aromatase inhibitor was effective for recurrent malignant GCT. We also review the literature for further management of this tumor. Because GCT of the ovary is rare, it will be necessary to elucidate the clinical phenotype and establish treatment protocols by accumulating and analyzing more patients. PMID:20947718

Bleomycin is a first-line clinically used antitumor antibiotic for effective treatment of certain types of cancer in combination with other antitumor agents. Its action is affected by bleomycin hydrolase (BLH), DNA repair enzymes, membrane transport proteins and other cellular factors. To clarify whether BLH confers the resistance to bleomycin in tumor cells, it is necessary to further investigate the roles of BLH and its combination with other factors such as caveolin-1 in the action of bleomycin. In this study fourteen human cell lines were used for determination of bleomycin action and roles of BLH and caveolin-1. The relationship between action of bleomycin and cellular amount of BLH was detected by the MTT method and western blotting in the human leukemia cell line HL-60, HeLa cervical cancer cells and HaCaT immortalized keratinocyte cells. The sensitivity to bleomycin was increased in HeLa cells after knockdown of BLH mRNA by RNA interference. There is no relationship between caveolin-1 levels and action of bleomycin, although the distribution of the cell cycle was altered in the caveolin-1-knockdown HeLa cells after treatment with bleomycin. In addition, regulation of BLH and caveolin-1 expression in HeLa and HaCaT cells was observed in a concentration-dependent manner after exposure to bleomycin. In conclusion, bleomycin hydrolase is one of the biomarkers for determination of bleomycin action. Although caveolin-1 can respond to bleomycin treatment, it is unrelated to bleomycin sensitivity. PMID:23076812

A new surface treatment technique for niobium (Nb) Superconducting Radio Frequency (SRF) cavities called Buffered Electropolishing (BEP) has been developed at JLab. It was found that BEP could produce the smoothest surface finish on Nb samples ever reported in the literature. Experimental results revealed that the Nb removal rate of BEP could reach as high as 4.09 um/min. This is significantly faster1 than that of the conventional electropolishing technique employing an acid mixture of HF and H2SO4. An investigation is underway to determine the optimum values for all relevant BEP parameters so that the high quality of surface finish achieved on samples can be realized within the geometry of an elliptical RF cavity. Toward this end, single cell Nb cavities are being electropolished with BEP electrolyte at both CEA-Saclay and JLAB. These cavities will be RF tested and the results will be reported through this presentation.

Feline head and neck squamous cell carcinoma (SCC) is a loco-regional disease harbouring a poor prognosis. The complex anatomic location precludes aggressive surgical resection and tumours recur within weeks to few months. Response to chemotherapy and local control after radiation therapy has been disappointing. In this study, a multimodal approach including medical treatment (thalidomide, piroxicam and bleomycin), radiation therapy (accelerated, hypofractionated protocol) and surgery was attempted in six cats. Treatment was well tolerated. Three cats with sublingual SCC were alive and in complete remission at data analysis closure after 759, 458 and 362 days. One cat with laryngeal SCC died of renal lymphoma after 51 days and the other with maxillary SCC died of a primary lung tumour 82 days after diagnosis. In both cats, the SCC was in complete remission. Only one cat developed metastases after 144 days. These encouraging preliminary results merit further evaluation in future trials. PMID:22443464

...suppliers as they enter the market; 15. Suspend reader suppliers...accurately denominates U.S. currency; b. Interact with verified...reader is based on the free market and personal choice and that...The Board pays BEP for its currency-related expenses,...

The block polyethers PEO-PPO-ph-PPO-PEO (BPE) and PPO-PEO-ph-PEO-PPO (BEP) are synthesized by anionic polymerization using bisphenol A as initiator. Compared with Pluronic P123, the aggregation behaviors of BPE and BEP at an air/water interface are investigated by the surface tension and dilational viscoelasticity. The molecular construction can influence the efficiency and effectiveness of block polyethers in decreasing surface tension. BPE has the most efficient ability to decrease surface tension of water among the three block polyethers. The maximum surface excess concentration (?(max)) of BPE is larger than that of BEP or P123. Moreover, the dilational modulus of BPE is almost the same as that of P123, but much larger than that of BEP. The molecular dynamics simulation provides the conformational variations of block polyethers at the air/water interface. PMID:22954368

Recent experimental results have indicated that Buffered Electropolishing (BEP) is a promising candidate for the next generation of surface treatment technique for Nb superconducting radio frequency (SRF) cavities to be used in particle accelerators. In order to lay the foundation for using BEP as the next generation surface treatment technique for Nb SRF cavities, some fundamental aspects of BEP treatments for Nb have to be investigated. In this report, recent progress on BEP study at JLab is shown. Improvements on the existing vertical BEP are made to allow water cooling from outside of a Nb single cell cavity in addition to cooling provided by acid circulation so that the temperature of the cavity can be stable during processing. Some investigation on the electrolyte mixture was performed to check the aging effect of the electrolyte. It is shown that good polishing results can still be obtained on Nb at a current density of 171 mA/cm when the BEP electrolyte was at the stationary condition and was more than 1.5 years old.

Bleomycin is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas, and squamous cell carcinomas of the cervix, head, and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug with other types of cancers. Previously, we documented that the Saccharomyces cerevisiae L-carnitine transporter Agp2 is responsible for the high affinity uptake of polyamines and of the polyamine analogue bleomycin-A5. Herein, we document that the human L-carnitine transporter hCT2 encoded by the SLC22A16 gene is involved in bleomycin-A5 uptake, as well as polyamines. We show that NT2/D1 human testicular cancer cells, which highly express hCT2, are extremely sensitive to bleomycin-A5, whereas HCT116 human colon carcinoma cells devoid of detectable hCT2 expression or MCF-7 human breast cancer cells that only weakly express the permease showed striking resistance to the drug. NT2/D1 cells accumulated fluorescein-labeled bleomycin-A5 to substantially higher levels than HCT116 cells. Moreover, L-carnitine protected NT2/D1 cells from the lethal effects of bleomycin-A5 by preventing its influx, and siRNA targeted to hCT2 induced resistance to bleomycin-A5-dependent genotoxicity. Furthermore, hCT2 overexpression induced by transient transfection of a functional hCT2-GFP fusion protein sensitized HCT116 cells to bleomycin-A5. Collectively, our data strongly suggest that hCT2 can mediate bleomycin-A5 and polyamine uptake, and that the rate of bleomycin-A5 accumulation may account for the differential response to the drug in patients. PMID:20037140

A metagenomic library of activated sludge was screened for bleomycin resistance genes. Two genes were identified that differed greatly from each other, from the genes of bleomycin-producing actinomycetes, and from those of clinical isolates. Therefore, the nonclinical environment is a rich reservoir...

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 amoun...

The combined effect of bleomycin and the polyene antibiotic, pentamycin, upon the survival of EMT6 tumour cells has been studied both in vitro and in vivo. During growth of the cells as a monolayer in vitro, a very marked potentiation of bleomycin action is seen during the exponential and early plat...

The aim of this study was to evaluate the clinical significance of the serum Bepridil (Bep) concentration (SBC) for safely managing patients with atrial tachyarrhythmias (AT). Methods and Results: SBC was measured in 41 patients with AT. The patients were administrated Bep for more than 4 weeks at same dose. They were divided into 2 groups according to their SBC: a high-SBC group (HSBC) of 11 patients with an SBC>500 ng/ml or a low-SBC group (LSBC) of 30 patients with an SBC<500 ng/ml. Age, underlying heart disease, cardiac function, dose of Bep did not differ between groups. Only the QT interval was significantly longer in the HSBC than in the LSBC (0.50±0.09 vs. 0.43±0.05, p=0.0067). Patients with QT >0.5 were more prominent in the HSBC (36% vs. 6.3%, p=0.014) and torsade de points (TdP) occurred in only one patient in the HSBC. Conclusions: In patients treated with Bep, measurement of SBC appears to be useful for preventing proarrhythmias. Patients with a high SBC but a normal QT interval may have a latent risk for QT prolongation and TdP when bradycardia or low potassium occurs. Reduction of Bep dose should be considered in such patients for the safe management.   

Background: Recent reports suggest angiotensin receptor blockers (ARBs) and some antiarrhythmic agents affect atrial remodeling in atrial fibrillation (AF). We evaluated the effect of combination therapy with olmesartan (Olm) and bepridil (Bep) in a canine model of AF. Methods and results: An atrial stimulation device was implanted in 10 dogs undergoing 6-week pacing at 400bpm. They were divided into Olm (2mg/kg/day) (n=5) and Olm+Bep (Olm, 2mg/kg/day; Bep, 10mg/kg/day) groups (n=5). Atrial effective refractory period (AERP), conduction velocity (CV), and AF inducibility were evaluated weekly, and hemodynamics, atrial histology, and mRNA expression and protein expression of ion-channel and gap junction-related molecules at 6weeks. Data were compared between groups and with non-pacing contr...

As a compensation of Gaussian approximation applied to an impulsive noise for estimating its disturbance effects on communication systems, impulsiveness correction factor (ICF) has been developed. ICF is defined by the ratio of the interfering noise power to the Gaussian noise power that causes the same degradation in bit error probability (BEP). Amplitude probability distribution (APD) of an interfering noise is also known to have a good correlation to the BEP of disturbed systems. In this paper, relation between ICF and APD is discussed to develop a simple expression.   

The effects of separate and combined application of the cytostatic Bleomycin and X-radiation on the multiplication of the Ehrlich ascitic tumour cells in vivo and on the survival time of tumourous mice was examined by applying automatic, electronic cell counting. If this cytostatic is administered alone up to 100 mg/kg the growth curve of the EAT-cells shows, after a 24 hours' delay, hardly any difference to that of untreated tumour cells. The separate administration of such Bleomycin doses and the separate X-radiation of the EAT cells with doses of up to 1000 rad had no significant influence on the survival time of tumourous mice. The combined application of Bleomycin and X-radiation elongates the 50%-survival time of the tumourous mice. If the X-radiation takes place 12 hours after the Bleomycin treatment the animals survive longer than is the case with simultaneous treatment. Although no dose effect curves could be set up the results obtained let assume a synergistic effect of Bleomycin and irradiation which is especially significant if the radiation is carried out 12 hours after a Bleomycin treatment. The reasons of this are assumed to lie in the increased radiation sensitivity of the tumour cells caused by the bleomycin-induced partial synchronisation of the EAT cells.

The intraperitoneal administration of cyclophosphamide or bleomycin to BALB/c mice resulted in lung cell damage followed by cellular proliferation, which was quantitated by measuring the increase in thymidine incorporation into pulmonary DNA. We have previously shown that administration of the antioxidant butylated hydroxytoluene produces lung damage that can be potentiated by both hyperoxia and thoracic X-irradiation. In the present study we show that hyperoxic exposure also potentiates bleomycin- and cyclophosphamide-induced acute lung damage. However, thoracic X-irradiation does not potentiate bleomycin- and cyclophosphamide-induced lung toxicity.

Interacting with bovine serum albumin (BSA), both the very weak carcinogenic hydrocarbon benzo(e)pyrene (Bep) and the powerful carcinogen benzo(a)pyrene (BaP) form pyrene-type compounds, indicating chemical modification at the bay region of the molecules. In constrast to the BaP-BSA reaction apparently similar to the metabolic activation to the bay region oxidation product, the BeP-BSA reaction differs from the known metabolic change of BeP which occurs at the K-region. While the BaP-BSA reaction also produces a BaP radical as well as other uv-fluorescent species, no BeP radical is formed in interaction with BSA and two sharp uv fluorescences at about 330 and 350 nm probably come from the higher excited states of BeP. Furthermore, from fluorescence and excitation spectral studies particularly at low temperature, it is suggested that the uv fluorescences at 320 to 380 nm of the BaP-BSA complex originate from a few distinct species. A new uv fluorescence at 330 nm (preferentially excited at 295 nm), as well as a new excitation peak at 325 nm for the longer wavelength uv fluorescences at 357 and 378 nm, has been found. The extract from the aqueous BaP-BSA solution also emits phosphorescence at 400-440 nm (excited at 310 nm) in EPA solution.

Transformation of rat embryo fibroblasts in vitro has been investigated using initiation with either benzo(a)pyrene (BaP), 7,12-dimethylbena(a)anthracent (DMBA) or benzo(e)pyrene (BeP) and promotion with either phorbol ester (TPA) or croton oil (Cr.Oil). The criteria used to assess in vitro transfor...

Flow numerical simulations in a low specific speed radial pump-turbine scale model are performed to investigate off-design operating conditions in generating mode. The Best Efficiency Point (BEP) and the runaway operating conditions at 10° guide vanes opening are addressed. The computational domain ...

We describe a rare case of a primary yolk sac tumor of the endometrium treated with a simple total hysterectomy without bilateral salpingo-oophorectomy and 3 cycles of the bleomycin, etoposide and cisplatin regimen.

... neck cancer (including cancer of the mouth, lip, cheek, tongue, palate, throat, tonsils, and sinuses) and cancer ... Bleomycin is also sometimes used to treat Kaposi's sarcoma related to acquired immunodeficiency syndrome (AIDS). Talk to ...

Concentrations were studied of /sup 58/Co in the solid Ehrlich ascites tumour, blood, muscle and bone of male Swiss mice administered as complexed with total bleomycin commercially available and its isolated fractions A/sub 2/, B/sub 2/, demethyl A/sub 2/, A/sub 1/, A/sub 5/, B/sub 4/ and bleomycinic acid. The tumour/non-tumour ratios were determined 24 hrs after injection of the complexes. The ratios for fraction A/sub 2/, B/sub 2/ and total bleomycin were very close to each other. The remaining fractions showed lower values of the ratios. These results suggest that it is unlikely that any of the fractions studied are superior to total labelled bleomycin with respect to tumour scintigraphy.

Co-57 bleomycin is a chemically stable and diagnostically useful radiopharmaceutical. Stoichiometric preparation of Co-bleomycin causes two chemically different complexes. Four kinds of chelates (A/sub 2/-type I, A/sub 2/-type II, B/sub 2/-type I and B/sub 2/-type II) are easily separated by silicagel thinlayer chromatography. Circular dichroism study of these chelates indicate that two types of complexes are conformational isomers. This chemical difference is assumed to cause the difference in the biological behaviour. The biodistribution study of each type of complexes, using tumor-bearing mice, showed higher tumor-to-blood ratios and tumor-to muscle ratios as compared to the clinical grade Co-bleomycin mixture. But the difference between two types were not so large, as expected. The similarity in biologic behaviour suggests that the groups on bleomycin molecule, which are concerned in chelate formation, do not take part in its binding to DNA.

Antitumoral effect of ethanolic extract of propolis (EEP) was demonstrated in mature mice-bearing Ehrlich carcinoma. Survival rate after EEP treatment was compared to that of bleomycin, given alone or in combination every two days for 36 days and followed up for 14 additional days. The survival rate at 50 days was 55% after EEP and 40% after bleomycin, while all the mice-treated with EEP + bleomycin combination demonstrated shorter survival than the controls. It is concluded that while the in vivo activity of bleomycin is reduced in the presence of cytochrome-C-reductase inhibitors (like some of the EEP components are), the antitumoral property of EEP in the tumored animal model studied is significant and lasting. PMID:2483616

Conditional ligase-deficient mutants of Saccharomyces cerevisiae were more sensitive than their parental (CDC9) strain to dose-dependent killing by bleomycin, even when mutant cells were pregrown and exposed to the antibiotic at permissive temperatures. Pretreatment incubation at the restrictive temperature (37/sup 0/C) under growing or nongrowing conditions enhanced bleomycin killing of both cdc9-1 and cdc9-9 mutants. This sensitization could be relieved by incubation at the permissive temperature before treatment.

A case of cancer en cuirasse is reported, deriving from a metastasizing malignant mixed tumor of the lacrimal gland. Based on histological criteria, the primary benigne prognosis of mixed tumors of lacrimal glands is discussed. According to sensitivity testing to cytostatic agents treatment with 375 mg of bleomycin achieved a recurrence-free interval of eight months. Pathogenesis of secondary effects are discussed (so-drug-induced called bleomycin-lung). PMID:88426

Diffusion tensor imaging (DTI) is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA), that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7) in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi-staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy.

We verified whether early resistance to treatment can be predicted in a subset of patients with very favourable, early stage Hodgkin lymphoma, treated with VBM (vinblastine, bleomycin and methotrexate) chemotherapy and involved-field radiotherapy, an effective combination with very low early and late toxicity. The relative tumour burden (rTB) was volumetrically measured from the staging computed tomography and analysed together with the parameters of pre-therapy evaluation in 61 patients enrolled into the protocol MH-1b of the Gruppo Italiano Studio Linfomi between 1996 and 2003. Early failure, codified by either less than complete remission (i.e. partial/null response or progression) or early relapse (within 12?months from the end of therapy), was considered as clinical expression of resistance to treatment. Logistic regression and failure-free survival were the statistical tools for the analysis. The rTB demonstrated to be the best predictor of early failure, outperforming every other pre-treatment parameter, International Prognostic Score included. With a mean rTB value of 44.964?±?34.788?cm(3) /m(2) in the 53 patients successfully treated and of 130.185?±?63.993?cm(3) /m(2) in the eight with early treatment failure, the risk of resistance showed fivefold and 10-fold increases at rTB of 52.002 and 74.497?cm(3) /m(2) , respectively. Only two patients relapsed more than 12?months after the end of therapy; both had a high initial rTB. The rTB is the best predictor of resistance also in the subset of patients with very favourable, early stage disease. Safe rTB limits are proposed for successful administration of VBM chemotherapy plus involved-field radiotherapy. Copyright © 2012 John Wiley & Sons, Ltd. PMID:23108910

The analysis of energetic particles and magnetic field measurements from the Ulysses spacecraft has shown that in a series of events, the energy density contained in the suprathermal tail particle distribution is comparable to or larger than that of the magnetic field, creating conditions of high-beta plasma. In this work we analyze periods of high-beta suprathermal plasma occurrences (@b"e"p>1) in interplanetary space, using the ratio (@b"e"p) of the energetic particle (20keV to ~5MeV) and magnetic field energy densities from measurements covering the entire Ulysses mission lifetime (1990-2009) in order to reveal new or to reconfirm some recently defined interesting characteristics. The main key-results of the work are summarized as follows: (i) we verify that high-beta events are detecte...

We develop a double-canyon radiation scheme (DCEP) for urban canopy models embedded in mesoscale numerical models based on the Building Effect Parametrization (BEP). The new scheme calculates the incoming and outgoing longwave and shortwave radiation for roof, wall and ground surfaces for an urban street canyon characterized by its street and building width, canyon length, and the building height distribution. The scheme introduces the radiative interaction of two neighbouring urban canyons allowing the full inclusion of roofs into the radiation exchange both inside the canyon and with the sky. In contrast to BEP, we also treat direct and diffuse shortwave radiation from the sky independently, thus allowing calculation of the effective parameters representing the urban diffuse and direct s...

Shape is one of the primary low-level image features in content-based image retrieval. In this paper we propose a new shape description method that consists of a rotationally invariant angular radial transform descriptor (IARTD). The IARTD is a feature vector that combines the magnitude and aligned phases of the angular radial transform (ART) coefficients. A phase correction scheme is employed to produce the aligned phase so that the IARTD is invariant to rotation. The distance between two IARTDs is defined by combining differences in the magnitudes and aligned phases. In an experiment using the MPEG-7 shape dataset, the proposed method outperforms existing methods; the average BEP of the proposed method is 57.69%, while the average BEPs of the invariant Zernike moments descriptor and the traditional ART are 41.64% and 36.51%, respectively.   

Aims: To elucidate how the nicotinic acetylcholine receptors expressed on bronchial and oral epithelial cells targeted by the tobacco nitrosamine (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) (NNK) facilitate carcinogenic transformation. Main methods: Since NNK-dependent transformation can be abolished by the nicotinergic secreted mammalian Ly-6/urokinase plasminogen activator receptor related protein-1 (SLURP-1), we compared effects of NNK and recombinant SLURP-1 on the expression of genes related to tumorigenesis in human immortalized bronchial and oral epithelial cell lines BEP2D and Het-1A, respectively. Key findings: NNK stimulated expression of oncogenic genes, including MYB and PIK3CA in BEP2D, ETS1, NRAS and SRC in Het-1A, and AKT1, KIT and RB1 in both cell types, which could be...

A 2 sup - level at 3.0 MeV in sup 8 B has been suggested from sup 7 Be+p elastic scattering measurements. The effect of such a level on the low-energy sup 7 Be(p,gamma) sup 8 B S factor is discussed, using R-matrix formulae with parameter values chosen to fit sup 7 Li+n data. It is concluded that the level must be broad (GAMMA sup 0>=4 MeV).

Erosion wear at various locations inside the volute casing of a centrifugal slurry pump has been measured for the flow of solid-liquid mixtures. The measurements show that the wear increases all along the volute periphery with increase in the amount of solids suspended in the mixture. It is also observed that the wear is smaller when the pump operates near the best efficiency point flowrate (BEP) compared to that at lower flowrate.   

Abstract in spanish El problema combinado de ubicación de almacenes y asignación óptima de inventarios es bastante difícil de plantear y resolver por métodos analíticos. Se busca determinar los almacenes que deben seleccionarse de un conjunto dado, así como los inventarios asociados a cada uno de ellos, para atender la demanda de un conjunto de artículos con un nivel de confianza dado. En este artículo se presenta un análisis del planteamiento del problema para atender la demanda d (more) e repuestos y dos metodologías heurísticas de solución. La primera, propuesta por los autores y llamada Búsqueda Exhaustiva con Poda, BEP, es basada en el recorrido del espacio de soluciones, eliminando durante la ejecución del algoritmo aquellas que sean dominadas, la cual puede ser usada en problemas con un número moderado de almacenes; y la segunda corresponde a la Búsqueda Tabú, la cual se usa cuando la BEP no se hace apropiada. Se realiza una comparación de ambas metodologías. Abstract in english The combined problem of location of warehouses and optimal allocation of inventories is quite difficult to pose and to solve by analytical methods. It is searched to determine the warehouses that must be selected of a given set, as well as the inventories associated to each one of them, to satisfy the demand of an article set with a given confidence level. It is presented an analysis of the generic exposition of the problem and a heuristic methodology of solution based on (more) the exploration of the space of solutions, eliminating during the execution of the algorithm, those that are dominated, which must used in problems with a moderated number of warehouses. The second, is the Tabu Search Method, which is used when BEP is inappropriate. A comparison between BEP and Tabu Search method is made.

Building energy performance (BEP) simulation is still rarely used in building design, commissioning and operations. The process is too costly and too labor intensive, and it takes too long to deliver results. Its quantitative results are not reproducible due to arbitrary decisions and assumptions made in simulation model definition, and can be trusted only under special circumstances. A methodology to semi-automate BEP simulation preparation and execution makes this process much more effective. It incorporates principles of information science and aims to eliminate inappropriate human intervention that results in subjective and arbitrary decisions. This is achieved by automating every part of the BEP modeling and simulation process that can be automated, by relying on data from original sources, and by making any necessary data transformation rule-based and automated. This paper describes the new methodology and its relationship to IFC-based BIM and software interoperability. It identifies five steps that are critical to its implementation, and shows what part of the methodology can be applied today. The paper concludes with a discussion of application to simulation with EnergyPlus, and describes data transformation rules embedded in the new Geometry Simplification Tool (GST).

To investigate small-scale transport and dispersion (T&D) within urban areas, we couple a large-eddy-simulation (LES)-based urban-scale fluid solver (EULAG), with the mesoscale Weather Research and Forecasting (WRF) system. The WRF model uses two different urban canopy models (UCM) to parameterize urban effects: a single-layer parameterization (SLUCM) and a multilayer building-effect parameterization (BEP) model coupled to Bougeault and Lacarrère planetary boundary-layer scheme. In contrast, EULAG uses the immersed-boundary (IMB) approach to explicitly resolve complex building structures. Here we present details of the downscaling transfer approach where the mesoscale conditions are used to supply initial and lateral boundary conditions for EULAG. We demonstrate its benefits and applicability to solve dispersion problems in the complex urban environment of Oklahoma City. The coupled modeling system is evaluated with data obtained from two intensive observation periods (IOP) of the Joint Urban 2003 experiment, representative for daytime convective (IOP6) and nighttime stable (IOP8) conditions. We assess the sensitivity of urban dispersion simulations to accuracy of the WRF-generated mesoscale conditions. The results show that WRF–BEP reproduces the observed mean near-surface and boundary-layer wind and temperature fields during daytime conditions, and provides accurate statistics during the nighttime more accurately than WRF-SLUCM. The EULAG model performance is exhibited with time-averaged and instantaneous peak concentration statistics. The improved statistics during IOP6 are achieved by using WRF-BEP indicating how important the proper meteorological conditions are to the accuracy of small-scale urban T&D modeling.

Interleukin (IL)-12 is a potent inducer of interferon (IFN)-gamma. We postulated that IL-12 would attenuate bleomycin-induced pulmonary fibrosis. To test this hypothesis, we administered IL-12 or murine serum albumin to bleomycin-treated mice by daily intraperitoneal injection until day 12. Mice treated with IL-12 demonstrated decreased hydroxyproline levels compared with control treated mice. Furthermore, administration of IL-12 led to a time-dependent increase in both lung and bronchoalveolar lavage fluid IFN-gamma. The antifibrotic effect of IL-12 could be attenuated with simultaneous administration of neutralizing anti-IFN-gamma antibodies. These findings support the notion that IL-12 attenuates bleomycin-induced pulmonary fibrosis via modulation of IFN-gamma production. PMID:11404251

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.

From 1978 to 1980, 52 patients underwent radical surgery for esophageal cancer, and they given radiotherapy of 300-500 rads and/or 50-100 mg of bleomycin prophylatically during the postoperative period. Of the total cases, five patients developed acute interstitial pneumonitis. All cases were controlled successfully by the administration of prednisolone, but one patient died of a complication of systemic aspergillosis. Pneumonitis occurred during the early course of irradiation, i.e. two cases during irradiation and one cases three days after irradiation. Pneumonitis also occurred with a low dose of bleomycin (70 mg) in two cases. Clinical signs of radiation pneumonitis were more severe in cases of esophageal cancer than in cases of lung cancer and breast cancer as had been previously reported. These results suggest that surgery for esophageal cancer tends to sensitize the lung and leads to pulmonary complications after radiotherapy and chemotherapy employing bleomycin.

Photochemical internalization (PCI) is a technique to improve the utilization of macromolecules (e.g. chemotherapeutic agents) in cancer therapy in a site-specific manner. The concept is based on the use of specially designed photosensitizers which localize preferentially in the membranes of endocytic vesicles. Upon exposure to light the photosensitizers induce the formation of reactive oxygen species such as singlet molecular oxygen. The photooxidation of the endocytic membranes leads to the release of the contents of the vesicles into the cytosol. In this way, macromolecules encapsulated by the vesicles will reach the cytosol and exert their biological activity instead of being degraded by lysosomal hydrolases. The utility of PCI for the treatment of malignant gliomas was investigated in vitro using an F98 rat glioma cell line. The cytotoxicity of 5-aminolevulinic acid (ALA) based PCI of bleomycin was compared to: (1) ALA-PDT, and (2) bleomycin. In all cases, monolayers were incubated in ALA, bleomycin, or ALA + bleomycin for 4 hours and were subsequently exposed to 635 nm light. Toxicity was evaluated using colony formation assays. F98 rat glioma cells in monolayer were found to be susceptible to the effects of both ALA-PDT and bleomycin. ALA-PDT was found to be particularly effective when light was delivered at a low irradiance of 5 mW cm-2. In this case, a radiant exposure of 20 J cm-2 resulted in only 4% survival. Bleomycin was found to be toxic at relatively low concentrations, incubation of F98 cells in 10 ?g ml-1 for 4 hours resulted in 1% survival. The PCI effect was found to be negligible for the parameters investigated in the F98 cell line suggesting that: (1) the incubation time was sub-optimal and/or (2) ALA was inappropriate for this application.

Fifteen patients with inoperable squamous cell carcinoma of the vulva were treated with Bleomycin and irradiation. Only 2 patients were also treated with vulvectomy and bilateral lymphadenectomy 2 weeks later. One patient survived more than 4 years without signs of recurrence, another survived 2 1/2 years and 2 more 18 and 12 months respectively. The rest died less than 6 months after the treatment. Three patients developed signs of lung fibrosis. Bleomycin and irradiation may render a tumor operable, but in most cases this regime merely aims at palliation.

Abstract Verrucas are often recalcitrant to conventional cryotherapy. Since 1970, intralesional bleomycin has been used off-label by dermatologists. But in some cases, the results of intralesional bleomycin were disappointing. Vincristine is a well-known vinca alkaloid antiblastic drug that has been used for treating hematological neoplasm and nephroblastomas. It was reported good efficacy of intralesional vincristine for treating nodular lesion in classic Kaposi sarcoma. Its use in epithelial neoplasm and Kaposi sarcoma may support its efficacy in recalcitrant verrucas. The three patients selected for the study presented severe verrucas on foot, and they had already undergone cryotherapy several times and there was no improvement. They got intralesional vincristine injection on their verr...

SummaryAimsPro-oxidant iron provides a potential measure of iron-catalysed oxidative stress in biological fluids. This study aimed, to investigate if the Bleomycin technique for measurement of pro-oxidant iron in biological fluids could be utilised for determinations in exhaled breath condensate (EBC). Secondly, to measure levels of pro-oxidant iron in EBC from asthmatics after exposure to polluting city environments. MethodsRetrospective analysis of samples of EBC and bronchoalveolar lavage fluid (BALF). Pro-oxidant iron levels were determined by the Bleomycin method. Transferrin levels were determined by radial diffusion immunoassay and lactoferrin by ELISA. Subjects: Patients undergoing surgery necessitating cardiopulmonary bypass, normal healthy controls, "healthy" smokers, and asthmat...

Conditional ligase-deficient mutants of Saccharomyces cerevisiae were more sensitive than their parental (CDC9) strain to dose-dependent killing by bleomycin, even when mutant cells were pregrown and exposed to the antibiotic at permissive temperatures. Pretreatment incubation at the restrictive tem...

Mice deficient in the plasminogen activator inhibitor-1 gene (PAI-1-/- mice) are relatively protected from developing pulmonary fibrosis from bleomycin administration. We hypothesized that one of the protective mechanisms may be the ability of the plasminogen system to enhance hepatocyte growth factor (HGF) effects, which have been reported to be anti-fibrotic in the lung. HGF is known to be sequestered in tissues by binding to extracellular matrix components. Following bleomycin administration, we found that HGF protein levels were higher in bronchoalveolar lavage fluid from PAI-1-/- mice compared to wild-type (PAI-1+/+) mice. This increase could be suppressed by administering tranexamic acid, which inhibits plasmin activity. Conversely, intratracheal instillation of urokinase into bleomycin-injured PAI-1+/+ mice to activate plasminogen caused a significant increase in HGF within bronchoalveolar lavage and caused less collagen accumulation in the lungs. Administration of an anti-HGF neutralizing antibody markedly increased collagen accumulation in the lungs of bleomycin-injured PAI-1-/- mice. These results support the hypothesis that increasing the availability of HGF, possibly by enhancing its release from extracellular matrix by a plasmin-dependent mechanism, is an important means by which activation of the plasminogen system can limit pulmonary fibrosis. PMID:14982862

A case of increased Ga-67 uptake in a patient with active acne vulgaris is reported. The scan was requested in a search for metastatic testicular carcinoma or bleomycin pulmonary toxicity. Careful clinical evaluation including physical examination was necessary in order to avoid an erroneous scan interpretation.

Paraquat, a quaternary ammonium bipyridyl herbicide, produces degenerative lesions in the lung after systemic administration to man and animals. The pulmonary toxicity of paraquat resembles in several ways the toxicity of several other lung toxins, including oxygen, nitrofurantoin and bleomycin. Alt...

The role of gender and sex hormones is unclear in host response to lung injury, inflammation, and fibrosis. To examine gender influence on pulmonary fibrosis, male and female rats were given endotracheal injections of either saline or bleomycin. Female rats showed higher mortality rates and more sev...

The present work evaluated the chemical composition and the DNA protective effect of the essential oils (EOs) from Lippia alba against bleomycin-induced genotoxicity. EO constituents were determined by Gas Chromatography/Mass Spectrometric (GC-MS) analysis. The major compounds encountered being citr...

The response of multicellular tumour spheroids of the EMT6 cell line to combinations of hyperthermia and Bleomycin (BLM) or Adriamycin (ADM) has been investigated. Using this model system, we have demonstrated enhanced BLM cytotoxicity at 43 degrees C and also heat-induced drug tolerance to BLM at 4...

We have examined the DNA cleavage specificity of a 1,10-phenanthroline-cuprous complex and find this agent to recognize the same sites and cleave with the same relative preferences as micrococcal nuclease. In contrast, DNase I and bleomycin-ferrous complex cleave the same 5000 bp D. melanogaster his...

NCI Contract/Grant No.______________ DCP Protocol No. ________________ IRB Protocol No. ___________________ PID No. ________________________Revised: January 6, 2012NCI Contract/Grant No.______________ DCP Protocol No. ________________ IRB Protocol

The optimal model for wireless optical communication system with Gaussian pointing loss factor is studied, in which the value of bit error probability (BEP) is prespecified and the optimal system parameters is to be found. For the superiority of augmented Lagrange method, the model considered is solved by using a classical quadratic augmented Lagrange algorithm. The detailed numerical results are reported. Accordingly, the optimal system parameters such as transmitter power, transmitter wavelength, transmitter telescope gain and receiver telescope gain can be established, which provide a scheme for efficient operation of the wireless optical communication system.

The absolute cross section sigma(E) for the radiative capture reaction sup 7 Be(p, gamma) sup 8 B at the center-of-mass energies E=0.32 to 2.61 MeV has been measured using a sup 7 Be target deposited on a Cu backing and observing the beta-delayed alpha-particles from sup 8 B. The backing causes a loss of less than 1% of the sup 8 B residual nuclides. The resulting astrophysical S(E) factor at zero energy, S(0)=18.4+-1.6 eV b, is consistent only with a restricted data set from previous work.

Cross sections for ^7Be+p elastic and inelastic scattering were measured at the HRIBF. Beams of ^7Be at 17 incident energies betweeen Ecm=0.5-3.4 MeV bombarded CH2 targets. Scattered protons were detected in a silicon-strip detector array covering ?cm=70^o-150^o. We have performed a multi-level R-matrix analysis of the combined cross sections (about 400 data points) to determine properties of states in ^8B. The inelastic scattering data provide evidence for positive-parity states that were previously unobserved but were predicted by theory. Results and implications will be discussed.

Since natural coloured sapphire (?-Al2O3) commands a high gem stone market price there is a need for a reliable method of identifying artificially coloured sapphire that has an inherently lower value. Diffusing beryllium into sapphire at high temperatures results in a coloured stone virtually indistinguishable from a natural one. Beryllium can occur naturally in sapphire but at levels of 10 ppma, which is difficult to determine in a non destructive way. It is possible to utilize nuclear reaction analysis techniques to determine the beryllium content in a macroscopically non destructive way. Kinematically ideal reactions are Be(p,?) and Be(p,d) which, for Ep = 0.5 to 0.9 MeV, exhibit distinct reaction product signatures well separated from other proton induced reactions in aluminium or oxygen. Due to the lack of comprehensive cross section data for the Be(p,?) and Be(p,d) reactions in the energy range of interest, a series of measurements were made at the Van de Graaff accelerator facility at Necsa to create a new data base. A further outcome of these measurements was a deviation in reported values for the non-Rutherfordian proton back-scatter cross section. These new data bases, which extend to Ep = 2.6MeV, can now facilitate a procedure for determining beryllium content in sapphire.

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.

Sunlit and shaded leaf separation proposed by Norman (1982) is an effective way to upscale from leaf to canopy in modeling vegetation photosynthesis. The Boreal Ecosystem Productivity Simulator (BEPS) makes use of this methodology, and has been shown to be reliable in modeling the gross primary productivity (GPP) derived from CO2 flux and tree ring measurements. In this study, we use BEPS to investigate the effect of canopy architecture on the global distribution of GPP. For this purpose, we use not only leaf area index (LAI) but also the first ever global map of the foliage clumping index derived from the multiangle satellite sensor POLDER at 6 km resolution. The clumping index, which characterizes the degree of the deviation of 3-dimensional leaf spatial distributions from the random case, is used to separate sunlit and shaded LAI values for a given LAI. Our model results show that global GPP in 2003 was 132 ± 22 Pg C. Relative to this baseline case, our results also show: (1) global GPP is overestimated by 12% when accurate LAI is available but clumping is ignored, and (2) global GPP is underestimated by 9% when the effective LAI is available and clumping is ignored. The clumping effects in both cases are statistically significant (p deciduous forest, evergreen conifer forest, deciduous conifer forest, shrub, C4 vegetation, and other vegetation, respectively. The global average of this ratio is 35%.

Pulmonary hypertension (PH) is a common and life-threatening complication of pulmonary fibrosis. Estradiol (E2) is protective in experimental PH, and its non-estrogenic metabolite 2-methoxyestradiol (2ME) prevents the development and retards the progression of monocrotaline-induced PH in male and female rats. However, the effects of E2 and 2ME on pulmonary fibrosis and associated PH have not been examined. Therefore, we compared the growth inhibitory effects of E2 and 2ME in human lung fibroblasts (hLFs) and pulmonary vascular smooth muscle cells (hPASMCs), and we investigated the effects of estrogen deficiency and 2ME on bleomycin-induced pulmonary fibrosis and PH. Intact and ovariectomized (OVX) female Sprague?Dawley rats were administered intratracheally either saline or bleomycin (15IU...

ABSTRACT Surfactant protein D (SP-D) has been used as a biomarker of lung inflammation. In rat, several types of enzyme-linked immunosorbent assay (ELISA) using polyclonal antibodies have been reported. The purpose of this study was the development of a sensitive ELISA for rat SP-D using monoclonal antibodies. The authors developed a sandwich ELISA using monoclonal antibodies that were obtained by immunizing with purified rat SP-D. The ELISA was evaluated by performance tests. Furthermore, concentrations of serum SP-D were measured in normal control and bleomycin-treated rats. The working range of ELISA was between 0.47 and 30 ng/mL. Different concentrations of added SP-D were recovered, between 94.1% and 102.8%. Serum SP-D levels of bleomycin-treated rats were significantly higher than th...

Bleomycin hydrolase is a cysteine protease that hydrolyzes the anticancer drug bleomycin. The homolog in yeast, Gal6, has recently been identified and found to bind DNA and to act as a repressor in the Gal4 regulatory system. The crystal structure of Gal6 at 2.2 {Angstrom} resolution reveals a hexameric structure with a prominent central channel. The papain-like active sites are situated within the central channel, in a manner resembling the organization of active sites in the proteasome. The Gal6 channel is lined with 60 lysine residues from the six subunits, suggesting a role in DNA binding. The carboxyl-terminal arm of Gal6 extends into the active site cleft and may serve a regulatory function. Rather than each residing in distinct, separable domains, the protease and DNA-binding activities appear structurally intertwined in the hexamer, implying a coupling of these two activities. 44 refs., 6 figs., 1 tab.

The induction of aneuploidy (numerical chromosome aberrations) in oocytes of Drosophila melanogaster by the antitumor drug bleomycin (BLM) was studied with the aneuploidy pattern method. The aneuploidy pattern obtained after feeding BLM at a concentration of 50 ..mu..g/ml to Drosophila females resembles the pattern obtained after X-irradiation (3000 R). This emphasizes the radiomimetic nature of BLM. In addition, new control material is presented. The new control pattern agrees well with that obtained earlier.

Introduction Chylothorax is a very rare complication of chronic lymphocytic leukemia. Presentation of case We describe the case of an 83-year old woman with chronic lymphocytic leukemia, complicated by recurrent chylothorax and ultimately treated by pleurodesis with bleomycin. Discussion There are several options for management of patients presenting with chylothorax due to chronic lymphocytic leukemia. Conclusion Pleurodesis is a reasonable and effective treatment modality for patients with refractory chylothorax. PMID:11012135

Idiopathic pulmonary fibrosis is the most prevalent chronic fibrosing lung disease. Peroxisome proliferator-activated receptors-gamma agonists provide potential therapy for fibrotic diseases of the lung. Peroxisome proliferator-activated receptors-alpha agonists may be helpful in the treatment of lung inflammatory diseases, however their therapeutic potential on the "fibro-proliferative" process and extracellular matrix accumulation in idiopathic pulmonary fibrosis has been less well studied. So, the present study was conducted to evaluate the anti-fibrotic effects of fenofibrate (peroxisome proliferator-activated receptors-alpha agonist) alone and in combination with rosiglitazone (peroxisome proliferator-activated receptors-gamma agonist) on lung injury induced by bleomycin administration. Oral administration of either rosiglitazone (5 mg/kg/d) or fenofibrate (100 mg/kg/d) for 14 days, attenuated the severity of bleomycin-induced lung injury and fibrosis through decreasing lung water contents, lung fibrotic grading, lung hydroxyproline contents and lung transforming growth factor-beta1 levels; with no significant difference between them. Combined low doses of rosiglitazone (1 mg/kg/d) and fenofibrate (30 mg/kg/d) provided more benefits than full separate doses of each on the deleterious effects accompanied bleomycin administration. These findings suggested the potential use of peroxisome proliferator-activated receptors-alpha ligands as anti-fibrotic agents in lung fibrosis. Additionally, the concurrent administration of fenofibrate and rosiglitazone in low doses has synergistic effect and enhanced the beneficial effects afforded by either fenofibrate or rosiglitazone. PMID:22659583

Monocyte chemoattractant protein-1 (MCP-1) is a proinflammatory chemokine and may play an important role in the development of pulmonary fibrosis. We examined a new therapeutic strategy that comprises the transfection of the mutant MCP-1 gene into skeletal muscles as a biofactory for anti-MCP-1 therapy against bleomycin-induced pulmonary fibrosis in mice. Overexpression of the mutant MCP-1 gene at 10-14 days after intratracheal instillation of bleomycin resulted in decreased DNA damage, apoptosis, and pulmonary fibrosis at 14 days. However, overexpression of the mutant MCP-1 at 0-4 days after bleomycin instillation did not result in decreased pathological grade, DNA damage, or apoptosis at 7 and 14 days. Because, in this model, inflammatory cell infiltration begins at 3 days and is followed by interstitial fibrosis, it is likely that MCP-1 has an important role to play in the development of fibrogenesis but not in the development of early lung inflammation. This method does not require the use of viral vector or neutralizing antibody, and, as such, it is possible to avoid problems regarding the pathogenicity of the viral vector or immunocomplex. This new strategy may be a beneficial method of treating pulmonary fibrosis from the viewpoint of clinical application. PMID:15064241

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 /sup 57/Co-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 /sup 57/Co-bleomycin A/sub 5/ 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 A/sub 5/ showed that the moments of visualization of the tumors varied in the different inoculated tumors in intervals from 3 to 48 h after application.

Abstract in english The effectiveness of an aqueous extract of Caryocar brasiliense (Caryocaraceae) Camb pulp, popularly known in Brazil as pequi, against clastogenicity induced by cyclophosphamide and bleomycin was evaluated using an in vivo mouse bone marrow cell micronuclei test, an in vitro Chinese hamster ovary cell (CHO-K1) chromosome aberration test and an in vitro antioxidant assay based on the oxidative damage to 2-deoxy-D-ribose (2-DR) induced by hydroxyl radicals (?OH) generated (more) by the reaction between ascorbic acid and (Fe III)-EDTA. In mouse bone marrow cells the extract showed a protective effect against micronuclei induced by cyclophosphamide and bleomycin but did not interfere with polychromatic bone marrow erythrocyte proliferation, except when the mice had been treated with the highest dose of cyclophosphamide. When CHO-K1 cells were pretreated by adding 0.01, 0.05 or 0.1 mL of extract per mL of cell culture medium 24 or 48 h before bleomycin or cyclophosphamide there was a protective effect against chromosome breaks and a significant decrease in the mitotic index (a measure of cytotoxicity) of the CHO-K1 cells. The extract also had a protective effect against oxidative hydroxyl radical damage to 2-DR. This study suggests that C. brasiliense pulp aqueous extract has anticlastogenic potential, possibly due to its antioxidative properties.

Present day use of mobile phones is ubiquitous. This causes some concern for human health due to exposure to high-frequency electromagnetic fields (HFEMF) from mobile phones. Consequently, we have examined the effects of 2.45 GHz electromagnetic fields on bacterial mutations and the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutations. Using the Ames test, bacteria were exposed to HFEMF for 30 min at specific absorption rates (SARs) from 5 to 200 W/kg. In all strains, there was no significant difference in the frequency of revertant colonies between sham exposure and HFEMF-exposed groups. In examination of mutations of the HPRT gene, Chinese hamster ovary (CHO)-K1 cells were exposed to HFEMF for 2 h at SARs from 5 to 200 W/kg. We detected a combination effect of simultaneous exposure to HFEMF and bleomycin at the respective SARs. A statistically significant difference was observed between the cells exposed to HFEMF at the SAR of 200 W/kg. Cells treated with the combination of HFEMF at SARs from 50 to 200 W/kg and bleomycin exhibited increased HPRT mutations. As the exposure to HFEMF induced an increase in temperature, these increases of mutation frequency may be a result of activation of bleomycin by heat. We consider that the increase of mutation frequency may be due to a thermal effect.   

Vinblastine, bleomycin, methotrexate (VBM) combination chemotherapy (CT) with involved field radiotherapy (IFRT) was first described by the Stanford group as an active regimen in early stage Hodgkin's disease (HD). Here, we report our retrospective experience of a modified VBM schedule + IFRT in a similar group of patients. From 1988, 49 patients with stage I-IIA HD received vinblastine (VBL) 6 mg/m2, bleomycin (BLM) 10 IU/m2, methotrexate (MTX) 30 mg/m2 day 1,8 every four weeks for three cycles; IFRT was delivered four weeks later followed by three additional cycles of VBM with a dose reduction of BLM (6 IU/m2). The regimen was well tolerated, with grade 3-4 neutropenia occurring in 20 patients. No acute or late pulmonary toxicity was recorded in our series. Estimated Freedom from Progression (FFP) and Overall Survival (OS) at five years are 75% (95% CI, 60.1%-92.2%) and 85% (95% CI, 73.6%-98.1%), respectively. In this retrospective analysis, VBM + IFRT treatment with bleomycin dose reduction seems safe and active. Such combination could be considered as first line treatment for early stage HD patients with favorable prognosis and/or not suitable for anthracyclines-containing regimens. PMID:14738143

Urban optical wireless communication (UOWC) systems are considered a last-mile technology. UOWC systems use the atmosphere as a propagation medium. To provide a line of sight the transceivers are placed on high-rise building. However, dynamic wind loads, thermal expansion, and weak earthquakes cause buildings to sway. These sways distort the alignment between transmitter and receiver, causing pointing errors, the outcome of which is fading of the received signal. Furthermore, atmospheric turbulence causes fluctuations in both the intensity and the phase of the received signal, resulting in impaired link performance. A bit-error probability (BEP) model is developed that takes into account both building sway and turbulence-induced log amplitude fluctuations (i.e., fading of signal intensity) in the regime in which the receiver aperture, D0, is smaller than the turbulence coherence diameter, d0. It is assumed that the receiver has knowledge about the marginal statistics of the signal fading and the instantaneous signal-fading state. PMID:12656506

SummaryBackgroundPrevious research has shown that innate immune system was more important than the acquired immune system in the pathogenesis of COPD. LL-37 is the only human cathelicidin identified so far. As an integral part of the innate immune system, besides antibacterial activity, its chemotactic activity, damage repairing, influencing apoptosis and its cytotoxicity are attracting peoples attention. The aim of the present study was to evaluate role of LL-37 in the pathogenesis of COPD. MethodsELISA and immunohistochemistry were applied to investigate the expression of LL-37 in induced sputum and lung tissue of COPD patients. Bronchial epithelial cell (BEP2D) and alveolar epithelial cell (A549) were treated with LL-37 synthesis polypeptide in vitro to assess the role of LL-37 in infla...

Reactivity of polycyclic aromatic compounds (PACs) adsorbed on natural aerosol particles exposed to different atmospheric oxidants (O3, OH and NO2/O3 mixture) was studied. Decay of polycyclic aromatic hydrocarbons (PAHs) and formation/decay of oxygenated PAHs (OPAHs) and nitrated PAHs (NPAHs) were monitored. Overall, benzo[a]pyrene appeared to be the most reactive PAH (degradation of 50%). Only its nitrated derivative, 6-nitrobenzo[a]pyrene, was significantly formed explaining just 0.4% of reacted benzo[a]pyrene. No other nitrated or oxygenated benzo[a]pyrene derivatives were detected. Interestingly, B[e]P and In[1,2,3,c,d]P, which are usually considered as quite stable PAHs, also underwent decay in all experiments. In presence of O3, ketones were significantly formed but their amount was ...

Bank note producers are working to thwart the threat of counterfeit notes created using high resolution, digital image processing software and color output devices such as inkjet printers, color copiers, and scanners. Genuine notes must incorporate better overt and machine-readable security features that will reduce the chance of counterfeit notes being passed. Recently, Canada and the United States introduced newly designed bank notes that are intended to enable the general public to more easily distinguish genuine notes from counterfeits. The Bank of Canada (BoC) and the U.S. Department of Treasury"s Bureau of Engraving and Printing (BEP) have conducted similar market research projects to explore target audiences' perceptions and attitudes towards currency design and security features. This paper will present a comparative analysis of the two research projects, both of which were conducted using similar methodology. The results of these research studies assist in the selection of security features for future generations of bank notes.

Abstract in english A novel electrochemical sensor has been developed for the determination of nimesulide. The sensor is based on the NIM- molybdophosphoric acid (MPA) as the electroactive material in PVC matrix in presence of bis(2-ethyl hexyl) phthalate (BEP) as a plasticizer. The sensor showed a fast, stable, near Nernstian response for 1 ´ 10-2 -1 ´ 10-6 M NIM over the pH range 5 - 8 with a slope 55.6 ±0.5m V/decade and the response time is (more) e common ions show negligible interferences. The sensor was successfully applied for the determination of NIM in tablet and the results obtained are in good agreement with those obtained by the official method.

To investigate small-scale transport and dispersion (T&D) within urban areas, we couple a large-eddy-simulation (LES)-based urban-scale fluid solver (EULAG), with the mesoscale Weather Research and Forecasting (WRF) system. The WRF model uses two different urban canopy models (UCM) to parameterize urban effects: a single-layer parameterization (SLUCM) and a multilayer building-effect parameterization (BEP) model coupled to Bougeault and Lacarrere planetary boundary-layer scheme. In contrast, EULAG uses the immersed-boundary (IMB) approach to explicitly resolve complex building structures. Here we present details of the downscaling transfer approach where the mesoscale conditions are used to supply initial and lateral boundary conditions for EULAG. We demonstrate its benefits and applicabil...

Bolivia's deforestation emissions from land use change, including deforestation, account for 82% of its total greenhouse gas emissions. In recent years, soybean production has been the main cause of deforestation. There are currently no policies in place that will lead to a reduction in its deforestation rate or associated carbon emissions in the near-future. This analysis shows that in today's carbon-constrained world, a standing tree already has a potentially greater financial value than soybean production. Based on the results of this analysis, it is expected that the break even price (BEP) of carbon in Bolivia will be USD 4.43 in 2005 and USD 9.50 in 2012. Compensated Reduction (CR) creates large-scale financial incentives needed for forest protection at the national level and allows developing countries access to the global carbon market.

A Study on the design improvement of the TEP, BEP and Hoddown spring of a fuel assembly for SMART was performed. Cut boundary Interpolation Method was applied to get more accurate results of stress and strain distribution from the results of the coarse model calculation. The improved results were compared with that of a coarse one. The finer model predicted slightly higher stress and strain distribution than the coarse model, which meant the results of the coarse model was not converged. Considering that the test results always showed much less stress than the FEM and the location of the peak stress of the refined model, the pressure stress on the loading point seemed to contribute significantly to the stresses. Judging from the fact that the peak stress appeared only at the local area, the results of the refined model were considered enough to be a conservative prediction of the stress levels. The slot of the guide thimble screw was ignored to get how much thickness of the flow plate can be reduced in case of optimization of the thickness and also cut off the screw dent hole was included for the actual geometry. For the BEP, the leg and web were also included in the model and the results with and without the leg alignment support were compared. Finally, the holddown spring which is important during the in-reactor behavior of the FA was modeled more realistic and improved to include the effects of the friction between the leaves and the loading surface. Using this improved model, it was possible that the spring characteristics were predicted more accurate to the test results. From the analysis of the spring characteristics, the local plastic area controled the characteristics of the spring dominantly which implied that it was necessary for the design of the leaf to be optimized for the improvement of the plastic behavior of the leaf spring.

Sulfur dioxide (SO{sub 2}) is a common air pollutant, and inhaled SO{sub 2} in airway epithelium easily forms its soluble derivatives in vivo (bisulfite and sulfite), which are toxic to the respiratory system and related to the exacerbation of asthma. To investigate the effects of SO{sub 2} derivatives on the expressions of asthma related genes (MUC5AC and IL-13), the mRNA and protein levels of the two genes in cultured human bronchial epithelial (BEP2D) cells were analyzed using real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay, immunocytochemistry method and enzyme-linked immunosorbent assay (ELISA), respectively. The results showed that the mRNA expressions of MUC5AC and IL-13 were significantly increased at different concentrations of SO{sub 2} derivatives (0.0001, 0.001, 0.01, 0.1 and 1.0 mM), and the maximum appeared at 0.01 mM for MUC5AC (3.9-fold) or at 0.001 mM for IL-13 (4.7-fold). Meanwhile, SO{sub 2} derivatives significantly increased the mRNA levels at 0, 0.5, 1, 4 and 24 h post-exposure with the maximum at 4 h post-exposure (25-fold for MUC5AC and 41-fold for IL-13). Furthermore, the protein levels of MUC5AC and IL-13 in BEP2D cells were significantly increased at different concentrations and different time courses exposed to SO{sub 2} derivatives, along with the maximum at 4 h post-exposure. These results lead to a conclusion that SO{sub 2} derivatives can increase the expressions of MUC5AC and IL-13 genes on the transcription and translation levels, and it suggests that SO{sub 2} derivatives can induce mucus over-production and inflammation responses in human bronchial epithelial cells and may have relations with asthma diseases. This might be one of the possible mechanisms that SO{sub 2} aggravates asthma disease. (orig.)

Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced intestinal toxicity in mice, and although further investigations are necessary, it could be proposed as radioprotective agent. (authors)

Background Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro. Principal Findings Dodecahedron (Dd) structure is preserved at up to about 50°C at pH 7–8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37°C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin. Conclusions/Significance Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs.

Ethnopharmacological relevance: The flowers of Gentiana veitchiorum has been widely used in decoction form in the traditional medicine of Tibet against tussis, tracheitis, angina for their anti-inflammatory, antimicrobial and alexipharmic properties. Aim of the study: The aim of current study was to evaluate the therapeutic effects of Feining, a Chinese herbal formula (national invention patent: ZL200510042636.3) against pulmonary injuries and to clarify the mechanisms involved. Materials and methods: Experimental pulmonary injuries were induced by bleomycin (BLM) in rats with or without subsequent treatment of Feining or prednisone as positive control. The pulmonary injuries were evaluated by histological analysis. Also, the levels of superoxide dismutase (SOD), malondialdehyde (MDA), glu...

Abstract The incidence of Hodgkin lymphoma (HL) is rising among individuals infected with human immunodeficiency virus (HIV). Standard treatment regimens include vinblastine, which is known to cause neurotoxicity (NT) and is metabolized by cytochrome 3A4 (CYP3A4). This is inhibited by protease inhibitors (PIs), possibly increasing vinblastine exposure. There is little information on how interactions affect clinical outcome. A retrospective review of 32 patients with HIV-HL receiving chemotherapy with curative intent was performed to identify the frequency and risk factors for NT, hematologic toxicity (HT) and lung toxicity (LT). Treatment was: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in 90%, MOPP/ABV (mechlorethamine, vincristine, procarbazine, prednisone/doxorubicin, bleomy...

ABSTRACT Idiopathic pulmonary fibrosis (IPF) is characterized by interstitial lung infiltrates, dyspnea, and progressive respiratory failure. Reports linking telomerase mutations to familial interstitial pneumonia (FIP) suggest that telomerase activity and telomere length maintenance are important in disease pathogenesis. To investigate the role of telomerase in lung fibrotic remodeling, intratracheal bleomycin was administered to mice deficient in telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC) and to wild-type controls. TERT-deficient and TERC-deficient mice were interbred to the F6 and F4 generation, respectively, when they developed skin manifestations and infertility. Fibrosis was scored using a semiquantitative scale and total lung collagen was measured usi...

Sodium butyrate (NaB), a potent histone deacetylase inhibitor, induces cell cycle arrest and apoptosis in malignant cells. We investigated the effects on cellular proliferation in vitro when combining NaB with antineoplastic drugs commonly used to treat leukemias. Our results demonstrate that NaB increases the cytotoxic effects of cytarabine and etoposide, but not of bleomycin, doxorubicin, vincristine or methotrexate. These data suggest that NaB is a promising adjuvant therapeutic agent for the treatment of lymphoblastic leukemias, and provides a basis for further studies in this field.

Abstract Pregnancy complicated by endodermal sinus tumor of the ovary is a very rare event. We present a case report of a pregnant woman with a ruptured primary endodermal sinus tumor of the ovary that was diagnosed at 13-weeks of gestation. After right salpingo-oophorectomy had been performed the patient received four cycles of combination chemotherapy (bleomycin, etoposide, and cisplatin) starting at the 15th week of pregnancy. The patient did not have any evidence of tumor recurrence for 23-months. Her baby did not have any evidence of malformations and showed normal growth and development at 21-months of follow up.

Human fibroblast cells from two different progeroid syndromes, Werner syndrome (WS) and progeria, were established as immortalized cell lines by transfection with plasmid DNA containing the SV40 early region. The lineage of each immortalized cell line was confirmed by VNTR analysis. Each of the immortalized cell lines maintained its original phenotype of slow growth. DNA repair ability of these cells was also studied by measuring sensitivity to killing by uv or the DNA-damaging drugs methyl methansulfonate, bleomycin, and cis-dichlorodiamine platinum. The results showed that both WS and progeria cells have normal sensitivity to these agents.

Background:Combined-modality therapy is a promising approach to improve the therapeutic index of radiotherapy. However, these improvements could come at the cost of increased toxicities. Clinical trials evaluating anti-tumour efficacy of bevacizumab combined with radiotherapy have encountered unexpected side effects. This study is the first systematic evaluation of normal tissue toxicity triggered by anti-angiogenic agents combined with radiation therapy in mice.Methods:Effect of a mouse anti-VEGF antibody was monitored on acute toxicity studying radiation-induced intestinal ulceration (12?Gy TBI); on subacute toxicity using a model of oral mucositis (16.5?Gy); on late radiation injuries by monitoring lung fibrosis (bleomycin and 19?Gy).Results:Combination of irradiation ...

Abstract in portuguese Inúmeros trabalhos têm demonstrado que linfócitos de pacientes com síndrome de Down apresentam uma maior freqüência de aberrações cromossômicas quando expostos a radiação ionizante ou agentes químicos nas fases G0 ou G1 do ciclo celular, mas não em G2, quando comparados com controles normais. Para determinar a sensibilidade de linfócitos de pacientes com síndrome de Down, na fase G2, usou-se o radiomimético bleomicina em culturas de linfócitos de 24 pacie (more) ntes. Todos os pacientes mostraram trissomia livre do cromossomo 21 (47,XX + 21 ou 47,XY + 21). Indivíduos que apresentaram freqüência média de quebras cromatídicas por célula superior a 0,8 foram considerados sensíveis à droga. Nenhum controle apresentou suscetibilidade à bleomicina e entre os 24 pacientes com síndrome de Down somente um foi sensível à droga. Não se observou qualquer diferença significativa entre os dois grupos em relação às freqüências de quebras cromatídicas em linfócitos em G2, o que está de acordo com outros trabalhos. A distribuição das quebras induzidas pela bleomicina, em cada grupo cromossômico, foi igual para pacientes e controles. Nenhuma diferença significativa foi observada na resposta à bleomicina entre homens e mulheres, nos dois grupos. Provavelmente, o principal fator envolvido na sensibilidade cromossômica de linfócitos de pacientes com síndrome de Down seja a fase do ciclo celular na qual a célula é tratada. Abstract in english 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 (more) the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.

In this session, Session JP4, the discussion focuses on the following topics: Hematopoiesis Dynamics in Irradiated Mammals, Mathematical Modeling; Estimating Health Risks in Space from Galactic Cosmic Rays; Failure of Heavy Ions to Affect Physiological Integrity of the Corneal Endothelial Monolayer; Application of an Unbiased Two-Gel CDNA Library Screening Method to Expression Monitoring of Genes in Irradiated Versus Control Cells; Detection of Radiation-Induced DNA Strand Breaks in Mammalian Cells By Enzymatic Post-Labeling; Evaluation of Bleomycin-Induced Chromosome Aberrations Under Microgravity Conditions in Human Lymphocytes, Using "Fish" Techniques; Technical Description of the Space Exposure Biology Assembly Seba on ISS; and Cytogenetic Research in Biological Dosimetry.

Background Tolerance to collagen structures has been shown to inhibit the progression of autoimmune scleroderma and rheumatoid arthritis. More recently, tolerance induction to collagen type V (colV) in experimental models of lung transplantation was shown to ameliorate the complex pathology known as “chronic rejection.” The link between colV autoimmunity and progressive graft dysfunction and subsequent development of bronchiolitis obliterans syndrome (BOS) has been established in human lung transplant recipients. We hypothesized that intravenous injection of colV inhibits development of lung fibrosis in a bleomycin-induced lung injury mouse model. Methods Experimental animals were injected intravenously with saline or colV 10 days before intratracheal instillation of bleomyci...

Key agreement protocols are frequently based on the Diffie-Hellman protocol but require authenticating the protocol messages in two ways. This can be made by a cross-authentication protocol. Such protocols, based on the assumption that a channel which can authenticate short strings is available (SAS...

Communications and communications protocols will play an important role in mobile robot systems able to address real world applications. A poorly integrated 'stack' of communications protocols, or protocols which are poorly matched to the functional and p...

CTEP & CC Protocols - Credit Report Community Clinical Oncology Program Research Base Protocol Credit Assignment Approved, Active, and Closed Protocols Research Base Gynecologic Oncology Group (GOG) qry_Credit_Report_Output_HTML_GOG

...and 03-123; FCC 12-71] Misuse of Internet Protocol (IP) Relay Service; Telecommunications...Commission adopts a measure that prohibits Internet-Protocol (IP) Relay providers from...summary of the Commission's Misuse of Internet Protocol (IP) Relay Service;...

...Refresh the Record Regarding Misuse of Internet Protocol Relay Service AGENCY: Federal...refresh the record regarding misuse of Internet Protocol relay service. Further comments...of reducing or eliminating misuse of Internet Protocol Relay. DATES: Submit...

We present a quantum key distribution protocol based on four-level particles entanglement. Furthermore, a controlled quantum key distribution protocol is proposed by utilizing three four-level particles. We show that the two protocols are secure.

CTEP & CC Protocols - Credit Report Community Clinical Oncology Program Research Base Protocol Credit Assignment Approved, Active, and Closed Protocols Research Base Eastern Cooperative Oncology Group (ECOG) qry_Credit_Report_Output_HTML_ECOG

The simultaneous treatment with the cross-linking agent cisplatin, the radiomimetic antitumoral drug bleomycin, and the anti-metabolite drug 5-fluorouracil has been used as a regimen to treat patients with squamous cell carcinoma of the head and neck. Considering that these drugs interact directly with DNA, one of the important late-occurring complications from treatment of primary malignancies is the therapy-related secondary cancers as a result of the genotoxic activity of the drugs on normal cells. In this sense, the genotoxicity of this combination was evaluated using the wing somatic mutation and recombination test in Drosophila melanogaster. The mutant spots observed in marker-heterozygous and balancer-heterozygous flies were compared in order to quantitatively and qualitatively estimate the genotoxic effect of these drugs. Cisplatin (0.003 and 0.006mM), bleomycin (0.005 and 0.01mM), and both combinations preferentially induced recombinational events, while mutation is the major event regarding the genetic toxicity of 5-fluorouracil (0.025 and 0.05mM). The combination of these drugs produced synergistic and antagonistic genotoxic effects, depending on the concentrations used, which could impose a higher risk of secondary effects associated with their genotoxic effects, emphasizing the importance of long-term monitoring in patients being treated with these drugs. PMID:22640881

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)

During a period of 5 years, from 1977 to 1982, twenty five patients with tongue cancer were treated by radium needle implantation and bleomycin at Yamagata University Hospital. In this paper, authors analysed seventeen patients followed over two years. All had biopsy proven squamous cell carcinoma. According to the TNM system (UICC, 1978), primary tumor was classified into 4 cases of T1, 8 cases of T2 and 5 cases of T3. The main purpose of this study was to obtain a high local control rate and reduce subsequent regional lymphnode metastasis. Our curative treatment method was simultaneous combination of 70 Gy of brachy-therapy and 40 mg of bleomycin. The results of this study were as follows: 1. A control rate in the primary lesion was 91% (10/11) in survivors having survived more than 2 years. 2. Radioosteonecrosis of mandible was found in 6% (1/17) and transient ulcer formation in the primary site was observed in 35% (6/17) of patients treated. However, all patients were cured by conservative treatment. 3. This treatment method did not reduce subsequent lymph node metastasis.

A novel method for detecting possible DNA repair enzymes on sodium dodecyl sulfate-polyacrylamide gels by blotting them onto a damaged DNA-fixed membrane is presented. To prepare the membrane, highly polymerized calf thymus DNA immobilized on a nylon membrane is damaged chemically. Enzymes, either homogeneous or crude, that are possibly involved in the priming step of DNA repair are fractionated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and are renatured to active form by incubating the gel in an appropriate buffer. The renatured enzyme is then blotted onto the damaged DNA-fixed membrane, a process during which incision and/or excision are introduced to the damaged DNA by the enzymes. The incision and/or excision provide priming sites for repair DNA synthesis in the subsequent step in which the membrane is incubated with DNA polymerase in the presence of alpha-{sup 32}P-labeled substrate. The site of substrate incorporation on the membrane reflecting the molecular weight of the repair enzyme is finally visualized by autoradiography. The present technique is established using Escherichia coli exonuclease III and a DNA-fixed membrane treated with bleomycin or acid-depurinated. By application of this method, a priming factor (an exonuclease) involved in the initiation of bleomycin-induced DNA repair is detected in the extract of mouse ascites sarcoma cells, and thus the molecular weight of the enzyme is estimated. Some apurinic/apyrimidinic endonucleases of mammals are also detected by the present procedure.

Serial echocardiography to detect doxorubicin dose-related cardiotoxicity correlates poorly with endomyocardial biopsy-proven cardiotoxicity. To compare radionuclide ventriculography (RVG) and echocardiography for the assessment of left ventricular (LV) function in children with Hodgkin disease (HD) receiving doxorubicin, we studied 39 children with HD before radiotherapy, both early (? 2 adriamycin, bleomycin, vinblastine, and dacarbazine cycles) (group A; n=10) and late (? 6 adriamycin, bleomycin, vinblastine, and dacarbazine cycles) (group B; n=36) during treatment. Seven children were assessed twice. The patients underwent full clinical assessment, echocardiography, and RVG. In group A, LV ejection fraction (LVEF) was significantly lower when measured by RVG compared with echocardiography (PRVG (P=0.000). Paired analysis of children studied early and late showed a significant drop in LVEF by echocardiography (58.7 ± 7.3 vs. 52 ± 52.44%; P=0.04) and RVG (51.4 ± 2.6% vs. 47.2 ± 3.1%; P=0.004). The cumulative dose of doxorubicin inversely correlated with RVG-measured LVEF (r=-0.531; P=0.001). No correlation was found between LVEF measured by RVG and echocardiography (r=0.217; P=0.25). Cardiotoxicity occurred early and at low cumulative doses of doxorubicin in children with HD. RVG was more sensitive than echocardiography in detecting early impairment of LV function. We recommend baseline and serial assessment of LV function by RVG in children with HD receiving doxorubicin. PMID:21516011

Abstract in english 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 r (more) ats 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

In vivo cell electropermeabilization can be used alone or in combination with a hydrophilic, nonpermeant cytotoxic drug such as bleomycin (electrochemotherapy) to efficiently treat tumors. We used magnetic resonance imaging to detect rapid structural modifications in tumors treated by electroporation-based methods. Water diffusion coefficient (ADC), transverse relaxation time (T(2)) and tumor volume of fibrosarcomas xenografted on syngenic mice were measured upon 3 groups of 6 treated mice within the 48 hrs following ECT done with a normal (BE) or a high dose of bleomycin (HBE), and after irreversible electroporation (IRE), and in three control groups. As expected, the tumor volume increased in the control groups at 48 hrs (p ADC and T2 did not varied significantly in the control groups except for ADC decrease and T2 increase observed between 3 hrs and 24 hrs (p ADC increased significantly at 24 hrs (117.6%, p ADC increased earlier, at 10 hrs (119%, p ADC decreased significantly at 1 hrs (p ADC and T(2) changes in the treated tumors correlated with previous histological observations on the same tumor models. Noteworthy, ADC allowed the visualization of early and rapid changes in the treated tumors, when tumor volume monitoring was not yet able to detect any effect of the treatments. PMID:22712607

The moss Physcomitrella patens is unique among plant models for the high frequency with which targeted transgene insertion occurs via homologous recombination. Transgene integration is believed to utilize existing machinery for the detection and repair of DNA double-strand breaks (DSBs). We undertook targeted knockout of the Physcomitrella genes encoding components of the principal sensor of DNA DSBs, the MRN complex. Loss of function of PpMRE11 or PpRAD50 strongly and specifically inhibited gene targeting, whilst rates of untargeted transgene integration were relatively unaffected. In contrast, disruption of the PpNBS1 gene retained the wild-type capacity to integrate transforming DNA efficiently at homologous loci. Analysis of the kinetics of DNA-DSB repair in wild-type and mutant plants by single-nucleus agarose gel electrophoresis revealed that bleomycin-induced fragmentation of genomic DNA was repaired at approximately equal rates in each genotype, although both the Ppmre11 and Pprad50 mutants exhibited severely restricted growth and development and enhanced sensitivity to UV-B and bleomycin-induced DNA damage, compared with wild-type and Ppnbs1 plants. This implies that while extensive DNA repair can occur in the absence of a functional MRN complex; this is unsupervised in nature and results in the accumulation of deleterious mutations incompatible with normal growth and development. PMID:22210882

Purpose. -- The objective of this retrospective study was to discuss the epidemio-clinical criteria and the therapeutic results of metastatic nasopharyngeal carcinoma. Patients and methods. - The current study concerned 95 patients with histologically proven nasopharyngeal carcinoma who were metastatic at diagnosis or who had developed late metastasis. We reviewed the epidemio-clinical records of all the patients. Patients were treated with chemotherapy (BEC regimen: bleomycin, epirubicin and cisplatin or PBF regimen: bleomycin, 5-fluorouracil and cisplatin) and radiotherapy of pauci metastatic localizations (single or double) or bone metastasis with high risk of compression or fracture {+-}associated with locoregional radiotherapy for patients who were metastatic at diagnosis. Response was assessed according to the WHO criteria. Overall survival was calculated according to the Kaplan-Meier method. A long-term disease-free survival was defined from 36 months. Results. - There were 34 patients who were metastatic at diagnosis and 61 patients who had developed late metastasis. The mean age was 41.5 years (sex-ratio: 3.1). Bone metastases were the most frequent (83%). Objective and complete response rates were respectively 75% and 70%, and 32% and 16% for BEC and PBF regimens. Twenty-five patients received radiotherapy for pauci metastatic localizations, among whom 19 patients who were metastatic at diagnosis received locoregional irradiation. The overall survival probability was of 15% for three years. Eleven patients were long survivors (extremes: 36 and 134 months). Conclusion. - Therapeutic results were comparable to those reported in other series using platin combination chemotherapy. Radiotherapy of metastasis yielded to long-term survival. (authors)

The protocol template is a tool to facilitate rapid protocol development. It is not intended to supersede the role of the Protocol Principal Investigator in the authoring and scientific development of the protocol. It contains the language required in protocols submitted to the NCI, Division of Cancer Prevention (DCP). Please modify all sections as necessary to meet the scientific aims of the study and development of the protocol.

...Assessment Protocol and the Organizational Culture Assessment Instrument...and protocol for assessing organizational culture in prisons. The assessment...Diagnosing and Changing Organizational Culture which they based on...

Discusses how various Open Systems Interconnection (OSI) application layer protocols can be used together, along with the Presentation and Session protocols, to support the interconnection requirements of applications. Application layer protocol standards that are currently available or under development are reviewed, and the File, Transfer, Access, and Management protocol is described. (SD)

We propose a modeling framework for generating security protocol specifications. The generated protocol specifications rely on the use of a sequential and a semantical component. The first component defines protocol properties such as preconditions, effects, message sequences and it is developed as a WSDL-S specification. The second component defines the semantic aspects corresponding to the messages included in the first component by the use of ontological constructions and it is developed as an OWL-based specification. Our approach was validated on 13 protocols from which we mention: the ISO9798 protocol, the CCITTX.509 data transfer protocol and the Kerberos symmetric key protocol.

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.

The classically-enhanced father protocol is an optimal protocol for a sender to transmit both classical and quantum information to a receiver by exploiting preshared entanglement and a large number of independent uses of a noisy quantum channel. We detail the proof of a quantum Shannon theorem that gives the three-dimensional capacity region containing all achievable rates that the classically-enhanced father protocol obtains. Points in the capacity region are rate triples consisting of the classical communication rate, the quantum communication rate, and the entanglement consumption rate of a particular coding scheme. The classically-enhanced father protocol is more general than any other protocol in the family tree of quantum Shannon theoretic protocols. Several previously known quantum protocols are now child protocols of the classically-enhanced father protocol. Interestingly, the classically-enhanced father protocol gives insight for constructing optimal classically-enhanced entanglement-assisted quantum...

This paper proposes a MAC protocol for presence information discovery in ubiquitous networks. The proposed protocol is designed for proactive discovery in which wireless devices periodically broadcast packets containing presence information. The protocol is based on Framed Aloha. The objective of the protocol is to assure the discovery time of single-hop neighbors considering wireless collisions and also power consumption. In this paper, we show that the proposed protocol is able to assure specified discovery time in distributed networks with random topology.   

Use of formal techniques for verifying the security features of electronic commerce protocols would facilitate, the enhancement of reliability of such protocols, thereby increasing their usability. This paper projects the application of logic programming techniques for formal verification of a well referred security and transactions protocol, the NetBill. The paper uses ALSP (Action Language for Security Protocols) as an efficient formal specification language and SMODELS a model generator to formally analyze and plan attacks on the protocol.

Aerobic bacterial culture was used to compare the effectiveness of the current USDA footwear disinfection protocol for airplane passengers contacting livestock to a novel protocol. The current protocol consists of brushing and dipping shoe soles in 1% Virkon S. The number of bacteria was not different between shoes treated with the current protocol and untreated shoes. No shoes met the standard for disinfection after the current disinfection protocol was completed. The novel protocol consisted of brushing shoe soles, wiping soles with a cotton towel soaked in 1% Virkon S, and drying soles with paper towels. The number of bacteria was less (P<0.0001) on treated shoes compared to control shoes. Eighteen of 20 shoes (90%) cleaned using the novel protocol met the standard for disinfection. Direct comparison of the current and novel protocols found that the number of bacteria cultured was less (P<0.0001) after implementing the novel protocol compared to implementing the current protocol. Again, no shoes treated using the current protocol met the standard for disinfection after the current protocol was completed. Sixteen and 17 of 20 shoes (80--85%), respectively, met the standard for disinfection after the novel protocol was completed. Under conditions of this study, current US airport footwear disinfection protocols were inadequate to disinfect footwear when using aerobic bacteria as a marker for disinfection. We recommend implementation of the novel footwear disinfectant protocol for select passengers from international flights. PMID:15975673

Recent measurements and analyses of proton induced radiative-capture reactions in the vicinity of E sub p =100 keV performed at the Triangle Universities Nuclear Laboratory are used to calculate the thermonuclear reaction rates of relevance in astrophysical plasmas for the reactions: D(p, gamma ) sup 3 He, sup 7 Li(p, gamma sub 0 sub , sub 1 ) sup 8 Be, sup 9 Be(p, gamma sub 0 sub , sub 1 sub , sub 2 sub , sub 3 ) sup 1 sup 0 B, and sup 1 sup 1 B(p, gamma sub 0 sub , sub 1 ) sup 1 sup 2 C. Higher energy data from previous measurements were included when possible. The Maxwellian-averaged reaction rates, obtained using numerical integration techniques, are presented in tabular form as a function of temperature. Capture to the ground and excited states are treated separately, thus allowing the determination of inverse reaction rates for specified target states. The high temperature cut-offs of the reaction rate calculations are discussed. The results are compared to those presented in the recent NACRE compilatio...

The detection of lithium, boron and beryllium was performed using a nuclear microprobe. The ?-emission yields have been measured for the most favourable nuclear reactions: Li(?,7i(?, ?'?)7Li, Li(p,7i(p, p'?)7Li, (p,10B(p, ??)7Be and Li(p,7i(p, n?)7Be. The possible interferences and the minimum detection limits (MDL) are presented, at different energies and for a total integrated charge of 1 ?C Lithium and boron, studied by the reactions (p, p'?) and (p, ?), respectively, have been determined in silicated glasses, as trace elements and on the scale of few micrometers. In the case of beryllium, using the Be(p,9e(p, ??)6Li reaction, the MDL is calculated to be 1100 ppm for beryllium. This element has not been further studied in our glass samples. PIGE (Proton Induced Gamma-ray Emission) allows the simultaneous measurement of lithium, fluorine and sodium. Standardization curves were made for lithium and boron on the basis of natural and synthetic glasses and minerals. Our results point out high boron contents in rhyolitic obsidians from Eolian Islands (Italy), compared with other rhyolites. Concentrations in lithium, fluorine and boron were determined, for the first time, in glass inclusions trapped within primitive minerals of the 1906 eruption of Vesuvius (Italy).

Understanding the electron screening effect in the laboratory is critical for a correct interpretation of low-energy nuclear reactions in stars. Extensive studies of the electron screening effect in deuterated metals (54 metals) and other environments have been carried out in Bochum in the last 4 years. Experimental results of anomalous enhancements have been interpreted in terms of the Debye plasma model applied to quasi-free metallic electrons. For the d(d,p)t reaction in metallic environments, the variation of hydrogen solubility in the samples as a function of temperature has also been measured, showing an anti-correlation with screening enhancement as expected. Within this model, the deduced number of valence electrons per metallic atom also agrees with the corresponding number from the Hall coefficient. Recently, the expected temperature dependence of the screening potential has been verified together with the expected Zt scaling (with the metallic host) of the Debye radius. Preliminary results on the 7Li(p,?) and 6Li(p,?) reactions in Li2WO4 insulator, Li metal and PdLi alloys confirm the expected behaviour of the screening effect and further supports the applicability of the Debye model. Indeed, the proposed model also accounts for the high screening potential (Ue = 900+/-50 eV) observed in previous studies of the reactions 9Be(p,?) and 9Be(p,d), which was not understood at the time. A review of all these results will be presented.

Nuclear structure of {sup 7}Be, {sup 8}B and {sup 7,8}Li is studied within the ab initio no-core shell model (NCSM). Starting from high-precision nucleon-nucleon (NN) interactions, wave functions of {sup 7}Be and {sup 8}B bound states are obtained in basis spaces up to 10 h bar{Omega} and used to calculate channel cluster form factors (overlap integrals) of the {sup 8}B ground state with {sup 7}Be+p. Due to the use of the harmonic oscillator (HO) basis, the overlap integrals have incorrect asymptotic properties. We fix this problem in two alternative ways. First, by a Woods-Saxon (WS) potential solution fit to the interior of the NCSM overlap integrals. Second, by a direct matching with the Whittaker function. The corrected overlap integrals are then used for the {sup 7}Be(p,{gamma}){sup 8}B S-factor calculation. We study the convergence of the S-factor with respect to the NCSM HO frequency and the model space size. Our S-factor results are in agreement with recent direct measurement data. We also test the spectroscopic factors and the corrected overlap integrals from the NCSM in describing the momentum distributions in knockout reactions with {sup 8}B projectiles. A good agreement with the available experimental data is also found, attesting the overall consistency of the calculations.

Multiple-input multiple-output (MIMO) maximum-SNR (max-SNR) system employs the maximum ratio combiner (MRC) at the receiver side and the maximum ratio transmitter (MRT) at the transmitter side. Its performances highly depend on MIMO channel characteristics, which vary according to both the number of antennas and their distribution between the transmitter and receiver sides. By using the decomposition of the ordered Wishart distribution in the uncorrelated Rayleigh case, we derived a closed-form expression of the largest eigenvalue probability density function (PDF). The final result yields to an expression form of the PDF where polynomials are multiplied by exponentials; it is worth underlining that, though this form had been previously observed for given couples of antennas, to date no formally-written closed-form was available in the literature for an arbitrary couple. Then, this new expression permits one to quickly and easily get the well known largest eigenvalue PDF and use it to determine the binary error probability (BEP) of the max-SNR.   

Nuclear structure of {sup 7}Be, {sup 8}B and {sup 7,8}Li is studied within the ab initio no-core shell model (NCSM). Starting from the high-precision CD-Bonn 2000 nucleon-nucleon (NN) interaction, wave functions of {sup 7}Be and {sup 8}B bound states are obtained in basis spaces up to 10{h_bar}{Omega} and used to calculate channel cluster form factors (overlap integrals) of the {sup 8}B ground state with {sup 7}Be+p. Due to the use of the harmonic oscillator (HO) basis, the overlap integrals have incorrect asymptotic properties. We fix this problem in two alternative ways. First, by a Woods-Saxon (WS) potential solution fit to the interior of the NCSM overlap integrals. Second, by a direct matching with the Whittaker function. The corrected overlap integrals are then used for the {sup 7}Be(p,{gamma}){sup 8}B S-factor calculation. We study the convergence of the S-factor with respect to the NCSM HO frequency and the model space size. Our S-factor results are in agreement with recent direct measurement data.

The simultaneous treatment with the cross-linking agent cisplatin, the radiomimetic antitumoral drug bleomycin, and the anti-metabolite drug 5-fluorouracil has been used as a regimen to treat patients with squamous cell carcinoma of the head and neck. Considering that these drugs interact directly with DNA, one of the important late-occurring complications from treatment of primary malignancies is the therapy-related secondary cancers as a result of the genotoxic activity of the drugs on normal cells. In this sense, the genotoxicity of this combination was evaluated using the wing somatic mutation and recombination test in Drosophila melanogaster. The mutant spots observed in marker-heterozygous and balancer-heterozygous flies were compared in order to quantitatively and qualitatively esti...

For the differentiation of benign from malignant thyroidal disease, ultrasound displays anatomic but not histologic features. Other visualization techniques can be used including isotope scanning (radioiodine, 99m technetium, 241 americium fluorescence, 131 cesium, 67 gallium, 75 selenomethionine, 201 thallium, 32 phosphorus, 99m Tc-bleomycin, 197 mercury, 133 xenon), thermography, x-ray techniques (plain films, computed tomographic scan, xeroradiography, chest x-ray barium swallow, lymphography, angiography), and thyroid hormone suppression. Needle biopsy can be done by core biopsy (Vim-Silverman and drill biopsy), large needle biopsy for histologic processing and fine needle aspiration for cytologic interpretation. The latter is the safest, most reliable, and most cost-effective technique currently available to differentiate between benign and malignant thyroidal disease and has great promise for the future.

Intralesional chemotherapy for nonmelanoma skin cancer has existed for more than 5 decades. However, it is used so infrequently that recent consensus guidelines for the treatment of basal cell and squamous cell carcinoma do not include intralesional chemotherapy. Barriers to the use of intralesional chemotherapy include the off-label use of these agents, absence of therapeutic guidelines, a relatively small number of patients treated, and a lack of large, well-designed trials with long-term follow-up. Surgical intervention remains the gold standard for the treatment of nonmelanoma skin cancer; however, intralesional chemotherapy remains an option for well-selected patients who cannot or will not undergo surgery. The objectives of this article are to determine response rates and suggest reasonable treatment guidelines for the treatment of squamous cell carcinoma, keratoacanthoma, and basal cell carcinoma with the most widely available intralesional agents (methotrexate, 5-fluorouracil, bleomycin, and interferon). PMID:20605654

Changes in collagen metabolism were examined in 3 models of acute respiratory disease in rats. Fibrotic changes in the lungs of rats were provoked by exposing them to paraquat (intraperitoneal), ozone (inhaled), or bleomycin (intratracheally injected). After an interval sufficient to allow histologically discernible fibrosis to occur (6 to 7 days), lungs were removed from the rats, and apparent collagen synthesis rates were determined with cultured lung minces incubated in medium containing 3H-proline. Portions of the 3H-proline-labeled lung minces were then used for quantifying ratios of Type I to Type III collagen. There was no change in Type I/Type III collagen for total unlabeled collagen, nor was there any detectable increase of total collagen per lung after 1 week. We conclude that an early event in experimental acute respiratory disease is a marked increase in the relative synthesis of Type I collagen; this shift occurs before there is observable increased accumulation of collagen in the lung.

Abstract Bleomycin-glucuronide (BLMG) is the glucuronide conjugate of BLM. In the present study, BLMG was primarily enzymatically synthesized by using a microsome preparate separated from rat liver, labeled with 131I by iodogen method with the aim of generating a radionuclide-labeled prodrug, and investigated its bioaffinities with tumor-bearing Balb/C mice. Quality control procedures were carried out using thin-layer radiochromatography and high-performance liquid chromatography. Tumor growing was carried out by following Caco-2 cell inoculation into mice. Radiolabeling yield was found to be about 65%. Results indicated that 131I-labeled BLMG (131I-BLMG) was highly stable for 24 hours in human serum. Biodistribution studies were carried out with male Albino Wistar rats and colorectal aden...

Purpose To evaluate the effects of left gastric artery embolization (LGAE) on plasma ghrelin levels, abdominal fat, and body weight in beagles. Methods The institutional animal care and use committee approved this study. Fifteen healthy adult beagles (12 male and three female animals) were randomly divided into three experimental groups: LGAE was proceeded with mixed emulsion of bleomycin A5 hydrochloride and lipiodol (group A), and polyvinyl alcohol particles (group B). Transcatheter saline injections in the left gastric artery were performed as a control. Weight and fasting plasma ghrelin levels were obtained at baseline and at weekly intervals for 8?weeks after the procedure in all animals. All animals were scanned and measured by multidetector computed tomography at baseline and at wee...

AbstractObjective To investigate whether JAK-2 contributes to the pathologic activation of fibroblasts in patients with systemic sclerosis (SSc) and to evaluate the antifibrotic potential of JAK-2 inhibition for the treatment of SSc. Methods Activation of JAK-2 in human skin and in experimental fibrosis was determined by immunohistochemical analysis. JAK-2 signaling was inhibited by the selective JAK-2 inhibitor TG101209 or by small interfering RNA. Bleomycin-induced dermal fibrosis in mice and TSK-1 mice were used to evaluate the antifibrotic potential of specific JAK-2 inhibition in vivo. Results Increased activation of JAK-2 was detected in the skin of patients with SSc, particularly in fibroblasts. The activation of JAK-2 was dependent on transforming growth factor (TGF) and persisted ...

Forty patients with T[sub 2] cancer of the tongue treated with external irradiation plus radium implants at Aichi Cancer Center were reviewed retrospectively to analyze the influence of overall treatment time on local control. One hundred percent (11/11) local control was achieved in patients irradiated within 35 days, in contrast to only 52% (13/25) local control in those irradiated over 35 days. This result indicates that prolonged overall time is associated with loss of local control. This prolongation is mainly due to the prolonged interval between external and internal irradiation. The interval was likely to be longer because of enhanced acute radiation mucositis, especially in patients administered bleomycin during external irradiation. External irradiation should be followed by interstitial irradiation as soon as possible to keep overall time shorter. (author).

Solid tumors of various etiologies can be treated efficiently by electrochemotherapy (ECT), a combined use of electroporation (EP) and chemotherapeutic drugs, such as bleomycin and cisplatin. EP alone and ECT in particular, induce a profound reduction in tumor blood flow, which contributes to the antitumor effect. After EP and ECT, the time course of blood flow changes and follows the same two-phase pattern. The first rapid and short-lived vasoconstriction phase is followed by the second much longer-lived phase resulting from disrupted cytoskeletal structures and a compromised barrier function of the microvascular endothelium. In the case of ECT, however, tumor vascular endothelial cells are also affected by the chemotherapeutic drug, which leads to irrecoverable damage to tumor vessels an...

Abstract Evidence suggests epithelial-mesenchymal transition (EMT) as one potential source of fibroblasts in idiopathic pulmonary fibrosis. To assess the contribution of alveolar epithelial cell (AEC) EMT to fibroblast accumulation in vivo following lung injury and the influence of extracellular matrix on AEC phenotype in vitro, Nkx2.1-Cre;mT/mG mice were generated in which AECs permanently express green fluorescent protein (GFP). On days 17-21 following intratracheal bleomycin administration, -4% of GFP-positive epithelial-derived cells expressed vimentin or -smooth muscle actin (-SMA). Primary AECs from Nkx2.1-Cre;mT/mG mice cultured on laminin-5 or fibronectin maintained an epithelial phenotype. In contrast, on type I collagen, cells of epithelial origin displayed nuclear localization o...

Abstract We report on a child with a de novo deletion of approximately 12-Mb detected through array comparative genomic hybridization (CGH). The deletion involved chromosome bands 13q12.3-13q14.11 and determined the loss of -50 genes. A second deletion on chromosome 12p11.3p11.22 of 43-167-kb, including about 12 genes, was unlikely of clinical relevance because inherited from the asymptomatic father. The child had developmental delay, dysmorphisms, and many features reminiscent of ataxia-telangiectasia (A-T), as cerebellar ataxia, oculocutaneus telangiectasia, and recurrent upper airway infections. Atraumatic fractures of the metatarsus were noted. Moreover, this is a rare case of 13q deletion syndrome associated with peripheral blood white cells radiosensitivity to bleomycin, reminiscent ...

We analyzed the chromosomal aberrations involving telomeres in the progeny of mammalian cells exposed to the radiomimetic compound bleomycin (BLM) in order to determine if this antineoplastic drug induces long-term telomere instability. To this end, rat cells (ADIPO-P2 cell line, derived from adipose cells from Sprague-Dawley rat) were treated with a single concentration of BLM (2.5mg/ml), and chromosomal aberrations were analyzed 18h and 10 days after treatment by using PNA-FISH with a pan-telomeric probe [(TTAGGG)n repeats]. Cytogenetic analysis revealed a higher frequency of aberrations at 18h and 10 days after treatment in BLM-exposed cultures vs. untreated cultures, although the yield of BLM-induced aberrations 10 days after treatment decreased about 25% compared with the one at 18h a...

Abstract. Robova H, Rob L, Hrehorcak M, Zoban P, Prusa R. Endodermal sinus tumor diagnosed in pregnancy: a case report. Int J Gynecol Cancer 2007;17:914-916. Pure endodermal sinus tumor (EST) of the ovary is an uncommon germ cell tumor characterized by rapid growth. Its occurrence during pregnancy is extremely rare. The case of a 34-year-old woman with EST stage IC diagnosed in the 22nd week of gestation is presented. She received four cycles of cisplatin monotherapy during pregnancy. Further, three cycles of combination chemotherapy (cisplatin, bleomycin, and etoposide) were administered. Twenty-eight months posttreatment the patient was in complete remission with good health. A healthy female infant was delivered by cesarean section in the 35th week of pregnancy. The child showed normal ...

Acute abdomen with hemoperitoneum is a very rare entity in postmenopausal women due to gynecologic conditions. A 54-year-old, postmenopausal woman was brought to emergency department with severe abdominal pain. Physical examination revealed acute abdomen findings with 15?cm pelvic mass on the right adnexal region. Immediate exploratory laparotomy was performed. During laparotomy 1000?cc of bloodstained fluid, ruptured and actively bleeding large mass arising from right ovary was observed. Right salpingo-oopherectomy was performed in emergency conditions, and pathology report revealed an adult type of granulosa cell tumor. After this result, staging surgery was performed and patient was diagnosed as granulosa cell tumor stage 1?c. Cisplatin, etoposide, and bleomycin chemotherapy was given. Clinicians should be aware of granulosa cell tumors which may occur at any age and prone to rupture. Frozen section will be helpful in order to avoid incomplete surgeries especially in postmenopausal women presented with intra-abdominal bleeding. PMID:22973526

We show here that mammalian site-specific recombination and DNA-repair pathways share a common factor. The effects of DNA-damaging agents on cell lines derived from mice homozygous for the scid (severe combined immune deficiency) mutation were studied. Surprisingly, all scid cell lines exhibited a profound hypersensitivity to DNA-damaging agents that caused double-strand breaks (x-irradiation and bleomycin) but not to other chemicals that caused single-strand breaks or cross-links. Neutral filter elution assays demonstrated that the x-irradiation hypersensitivity could be correlated with a deficiency in repairing double-strand breaks. These data suggest that the scid gene product is involved in two pathways: DNA repair of random double-strand breaks and the site-specific and lymphoid-restricted variable-(diversity)-joining (V(D)J) DNA rearrangement process. We propose that the scid gene product performs a similar function in both pathways and may be a ubiquitous protein.

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 /sup 103/Ru 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 /sup 97/Ru. Ruthenium-97 has favorable physical properties that make it ideal for imaging applications: decay by electron capture; ..gamma.. 216 keV, 85%; t/sub 1/2/ 2.9 d. A novel method based on the reduction of Ru/sup 3 +/ to Ru/sup 2 +/ using stannous chloride was investigated for labeling BLM with /sup 97/Ru and/or /sup 103/Ru. In-vitro and in vivo comparisons of the product(s) with /sup 57/Co and /sup 67/Cu-labeled BLM were also carried out. 4 refs., 3 tabs.

Presentation of Hodgkin lymphoma (HL) is distinctive in the infected individual being more advanced, accompanied by B symptoms and the presence of extranodal disease particularly lymphadenopathy of the head and neck. Bone marrow involvement may be found in over 50% of cases. Virtually all co express gamma-herpesvirus. Phenotypically there is prominence of the mixed-cellularity and lymphocyte depleted histopathologic subtypes that define an aggressive clinical course in comparison to other variants. Prior to the induction of cART, median survival was only 1-2years. Notably the first chemotherapy trial using ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in 21 patients, without treating the viral infection, resulted in a 43% complete remission rate accompanied by severe haematol...

Thymosin ?4 (T?4) has been found to have several biological activities related to antiscarring and reduced fibrosis. For example, the anti-inflammatory properties of T?4 and its splice variant have been shown in the eye and skin. Moreover, T?4 treatment prevents profibrotic gene expression in cardiac and in hepatic cells in vitro and in vivo. In a recent study on scleroderma patients it was hypothesized that T?4 may exert a protective effect during human lung injury. In an ongoing study, we have explored the putative T?4 protective role in the lung context by utilizing a well-known in vivo model. We have observed significant protective effects of T?4 on bleomycin-induced lung damage, the main outcomes being the halting of the inflammatory process and a substantial reduction of histological evidence of lung injury. PMID:23045972

We evaluated the effect of hIFN? gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFN? gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFN?-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy-sensitive EW7 monolayers, the combination of hIFN&...

Previous studies have indicated that the methylvalerate subunit of bleomycin (BLM) plays an important role in facilitating DNA cleavage by BLM and deglycoBLM. Eleven methylvalerate analogues have been synthesized and incorporated into deglycoBLM congeners by the use of solid-phase synthesis. The effect of the valerate moiety in the deglycoBLM analogues has been studied by comparison with the parent deglycoBLM A(5) using supercoiled DNA relaxation and sequence-selective DNA cleavage assays. All of the deglycoBLM analogues were found to effect the relaxation of the plasmid DNA. Those analogues having aromatic C4-substituents exhibited cleavage efficiency comparable to that of deglycoBLM A(5). Some, but not all, of the deglycoBLM analogues were also capable of mediating sequence-selective DNA cleavage. PMID:21612932

Summary Around 20% of Hodgkin lymphoma (HL) patients are refractory to first-line therapy with ABVD (adriamycin-bleomycin-vinblastine-dacarbazine) or relapse after complete remission. Salvage regimens frequently have delayed courses or require dose-reduction because of haemotoxicity. We evaluated the IVOx (ifosfamide-etoposide-oxaliplatin) salvage regimen in terms of response rate, toxicity and stem-cell mobilization. Thirty-four patients with relapsed/refractory HL after anthracycline-containing chemotherapy prospectively received IVOx, consisting of ifosfamide (1500-mg/m2 days 1-3), etoposide (150-mg/m2 days 1-3) and oxaliplatin (130-mg/m2 day 1). Patients <65-years old received high-dose therapy followed by autologous stem-cell transplantation (HDT-ASCT). Response was assessed by comput...

A small sodium iodide scintillation detector was designed for insertion through a fiberoptic bronchoscope to detect and localize sites of deposition of cobalt-57 bleomycin in lung cancer. The detector was used in 40 diagnostic studies of 34 patients; 21 of the patients had tumors. We compared the sensitivity, specificity, accuracy, and predictive value of the detector to those of plain chest x-ray films and bronchoscopy in detecting tumors. Sensitivity and specificity for the detector were 68 percent and 80 percent, respectively; for bronchoscopy, 72 percent and 100 percent; and for roentgenograms, 80 percent and 53 percent. Sensitivity for the detector and bronchoscopy combined was 92 percent. The detector succeeded in locating nonvisible submucosal and extraluminal tumors, and may contribute to early diagnosis and more accurate staging of lung cancer.

Senescence represents an important barrier against cellular transformation. Here we show that CAPNS1 depletion impairs senescence induction both in BJ-ET H-Ras(v12) inducible human fibroblasts upon Ras induction and in HT1080 targeted to senescence by treatment with low doses of doxorubicin. We further show that CAPNS1 depletion is coupled to reduced levels of H2AX phosphorylation, not only in Ras(v12) induced BJ-ET fibroblasts, but also in a number of cellular systems upon genotoxic stress. In particular CAPNS1 depletion affects gamma-H2AX appearance or persistence in U2OS osteosarcoma cells 24 hours after MMC addition or UV light exposure; in HT1080 upon camptothecin treatment for 4 hours and 48 hours after addition of MMC; in MDA-MB-231, 24 hours after UV light exposure and 2 hours after bleomycin addition. Overall this study unveils a novel link between calpain, cellular senescence and DNA damage response. PMID:20107320

On the basis of superior outcomes from electrochemogene therapy (ECGT) compared with electrochemotherapy in mice, we determined the efficacy of ECGT applied to spontaneous canine neoplasms. Intralesional bleomycin and feline interleukin-12 DNA (fIL-12 DNA) injection combined with translesional electroporation resulted in complete cure of two recurrent World Health Organization stage T2bN0M0 oral squamous cell carcinomas (SCCs) and one T2N0M0 acanthomatous ameloblastoma. Three remaining dogs, which had no other treatment options, had partial responses to ECGT; one had mandibular T3bN2bM1 melanoma with pulmonary and lymph node metastases; one had cubital T3N0M1 histiocytic sarcoma with spleen metastases; and one had soft palate T3N0M0 fibrosarcoma. The melanoma dog had decrease in size of th...

This invention provides a method of increasing sensitivity of cells to cytotoxic effects of ionizing radiation which includes incubating the cells with spindle poison in suitable carrier at a concentration effective to inhibit the cells from progressing through G2 or M phases of the cell cycle for a time effective to inhibit division of the cell and then administering a cytotoxic dose of ionizing radiation to the cell. This invention also provides a method of treating a cancer patient which comprises administering to patient a spindle poison in suitable carrier in an amount effective to inhibit tumor cells in the patient from progressing through G2 or M phases of the cell cycle for an amount of time effective to inhibit division of the tumor cells and then administering a cytotoxic dose of ionizing radiation to the patient. This invention further provides a method for increasing the sensitivity of cells to bleomycin and a kit useful for treating cancer patients. (author) figs.

Abstract The International Prognostic Score (IPS) is the most widely used system to date for identifying risk groups for the outcome of patients with advanced Hodgkin lymphoma, although important limitations have been recognized. We analyzed the value of the IPS in a series of 311 patients with advanced classical Hodgkin lymphoma (cHL) (Ann Arbor stage III, IV or stage II with B symptoms and/or bulky masses) treated with first-line chemotherapy including adriamycin (adriamycin, bleomycin, vinblastine, dacarbazine [ABVD] or equivalent variants). In univariate and multivariate analyses, stage IV disease and age ? 45 years were the only factors with independent predictive significance for overall survival (OS) (p == 0.002 and p < 0.001, respectively). Stage IV was still significant for fre...

Radiotherapy combined with bleomycin in oil and tegafur and/or carmofur has already been shown markedly effective in those patients having rectal cancer as studied histologically (Okuyama et al. Tohoku J. Exp. Med. 143 : 503, 1984) as well as clinically (Hariu et al. Jap. Assoc. Gastrenterol. Surg., Hiroshima, 1983). In search for attainment of better effectiveness, carmofur suppositories were developed. Their pharmacokinetic analysis revealed a ten-time increment in the blood concentration of 5-FU as compared with tegafur suppositories. The clinical results in terms of reduction in tumor size, CEA titers and survival appeared to be improved. Histological studies on the surgical materials seemed promising, too. The probable clinical significance of carmofur suppositories may be that pre-operative radiotherapy of rectal cancers, and possibly those patients having their metastases to the liver organ be greatly expedited.

Background: Asbestos induces DNA and chromosomal damage, but the DNA repair pathways protecting human cells against its genotoxicity are largely unknown. Polymorphisms in XRCC1 have been associated with altered susceptibility to asbestos-related diseases. However, it is unclear whether oxidative DNA damage repaired by XRCC1 contributes to asbestos-induced chromosomal damage. Objectives: We sought to examine the importance of XRCC1 in protection against genotoxic effects of crocidolite and Libby amphibole asbestos. Methods: We developed a genetic model of XRCC1 deficiency in human lung epithelial H460 cells and evaluated genotoxic responses to carcinogenic fibers (crocidolite asbestos, Libby amphibole) and nongenotoxic materials (wollastonite, titanium dioxide). Results: XRCC1 knockdown sensitized cells to the clastogenic and cytotoxic effects of oxidants [hydrogen peroxide (H2O2), bleomycin] but not to the nonoxidant paclitaxel. XRCC1 knockdown strongly enhanced genotoxicity of amphibole fibers as evidenced by elevated formation of clastogenic micronuclei. Crocidolite induced primarily clastogenic micronuclei, whereas Libby amphibole induced both clastogenic and aneugenic micronuclei. Crocidolite and bleomycin were potent inducers of nuclear buds, which were enhanced by XRCC1 deficiency. Libby amphibole and H2O2 did not induce nuclear buds, irrespective of XRCC1 status. Crocidolite and Libby amphibole similarly activated the p53 pathway. Conclusions: Oxidative DNA damage repaired by XRCC1 (oxidized bases, single-strand breaks) is a major cause of chromosomal breaks induced by crocidolite and Libby amphibole. Nuclear buds are a novel biomarker of genetic damage induced by exposure to crocidolite asbestos, which we suggest are associated with clustered DNA damage. These results provide mechanistic evidence for the epidemiological association between XRCC1 polymorphisms and susceptibility to asbestos-related disease.

A prominent feature of fibrotic tissue in general and of lungs in particular is fibroblast proliferation and accumulation. In patients overcoming fibrosis, apoptosis limits this excessive cell growth. We have previously shown resistance to Fas-induced apoptosis of primary lung fibroblasts from mice with bleomycin-induced lung fibrosis, their escape from immune surveillance, and continued accumulation in spite of overexpression of the Fas death receptor. Cellular FLICE-like inhibitory protein (c-FLIP) is a regulator of cell death receptor-induced apoptosis in many cell types. We aimed to determine c-FLIP levels in myofibroblasts from fibrotic lungs and to directly assess c-FLIP's role in apoptosis and proliferation of primary lung myofibroblasts. c-FLIP levels were determined by apoptosis gene array, flow cytometry, Western blot, and immunofluorescence before and after down-regulation with a specific small interfering RNA. Apoptosis was assessed by caspase cleavage in Western blot and by Annexin V affinity labeling after FACS and tissue immunofluorescence. Proliferation was assessed by BrdU uptake, also using FACS and immunofluorescence. We show that myofibroblasts from lungs of humans with idiopathic pulmonary fibrosis and from bleomycin-treated versus normal saline-treated mice up-regulate c-FLIP levels. Using the animal model, we show that fibrotic lung myofibroblasts divert Fas signaling from apoptosis to proliferation and that this requires signaling by TNF receptor-associated factor (TRAF) and NF-?B. c-FLIP down-regulation reverses the effect of Fas activation, causing increased apoptosis, decreased proliferation, and diminished recruitment of TRAF to the DISC complex. This indicates that c-FLIP is essential for myofibroblast accumulation and may serve as a potential target to manipulate tissue fibrosis. PMID:22582174

Recent reports have suggested that metformin has anti-inflammatory and anti-tissue remodeling properties. We investigated the potential effect of metformin on airway inflammation and remodeling in asthma. The effect of metformin treatment on airway inflammation and pivotal characteristics of airway remodeling were examined in a murine model of chronic asthma generated by repetitive challenges with ovalbumin and fungal-associated allergenic protease. To investigate the underlying mechanism of metformin, oxidative stress levels and AMP-activated protein kinase (AMPK) activation were assessed. To further elucidate the role of AMPK, we examined the effect of 5-aminoimidazole-4-carboxamide-1-?-4-ribofuranoside (AICAR) as a specific activator of AMPK and employed AMPK?1-deficient mice as an asthma model. The role of metformin and AMPK in tissue fibrosis was evaluated using a bleomycin-induced acute lung injury model and in vitro experiments with cultured fibroblasts. Metformin suppressed eosinophilic inflammation and significantly reduced peribronchial fibrosis, smooth muscle layer thickness, and mucin secretion. Enhanced AMPK activation and decreased oxidative stress in lungs was found in metformin-treated asthmatic mice. Similar results were observed in the AICAR-treated group. In addition, the enhanced airway inflammation and fibrosis in heterozygous AMPK?1-deficient mice were induced by both allergen and bleomycin challenges. Fibronectin and collagen expression was diminished by metformin through AMPK?1 activation in cultured fibroblasts. Therefore metformin reduced both airway inflammation and remodeling at least partially through the induction of AMPK activation and decreased oxidative stress. These data provide insight into the beneficial role of metformin as a novel therapeutic drug for chronic asthma. PMID:23041647

There are currently few treatment options for pulmonary fibrosis. Innovations may come from a better understanding of the cellular origin of the characteristic fibrotic lesions. We have analyzed normal and fibrotic mouse and human lungs by confocal microscopy to define stromal cell populations with respect to several commonly used markers. In both species, we observed unexpected heterogeneity of stromal cells. These include numerous cells with molecular and morphological characteristics of pericytes, implicated as a source of myofibroblasts in other fibrotic tissues. We used mouse genetic tools to follow the fates of specific cell types in the bleomcyin-induced model of pulmonary fibrosis. Using inducible transgenic alleles to lineage trace pericyte-like cells in the alveolar interstitium, we show that this population proliferates in fibrotic regions. However, neither these cells nor their descendants express high levels of the myofibroblast marker alpha smooth muscle actin (Acta2, aSMA). We then used a Surfactant protein C-CreER(T2) knock-in allele to follow the fate of Type II alveolar cells (AEC2) in vivo. We find no evidence at the cellular or molecular level for epithelial to mesenchymal transition of labeled cells into myofibroblasts. Rather, bleomycin accelerates the previously reported conversion of AEC2 into AEC1 cells. Similarly, epithelial cells labeled with our Scgb1a1-CreER allele do not give rise to fibroblasts but generate both AEC2 and AEC1 cells in response to bleomycin-induced lung injury. Taken together, our results show a previously unappreciated heterogeneity of cell types proliferating in fibrotic lesions and exclude pericytes and two epithelial cell populations as the origin of myofibroblasts. PMID:22123957

blackwood b., alderdice f., burns k.e.a., cardwell c.r., lavery g.g. &o'halloran p. (2009) Protocolized vs. non-protocolized weaning for reducing the duration of mechanical ventilation in critically ill adult patients: Cochrane review protocol. Journal of Advanced Nursing 65(5), 957-964 Abstract Title. Protocolized vs. non-protocolized weaning for reducing the duration of mechanical ventilation in critically ill adult patients: Cochrane review protocol. Aim. This paper is a report of the protocol for a review to identify, critically appraise and synthesize the best current evidence supporting the use of weaning protocols compared to non-protocolized practice in liberating patients from mechanical ventilation. Background. Patients experiencing difficulty in weaning require a longer hospital...

High efficient routing is an important issue for the design of wireless sensor network (WSN) protocols to meet the severe hardware and resource constraints. This paper presents a comprehensive survey and comparison of routing protocols in WSNs. The first part of the paper surveys state-of-the-art routing protocols in WSNs from classical routing protocols to swarm intelligence based protocols. The routing protocols are categorized based on their computational complexity, network structure, energy efficiency and path establishment. The second part of the paper presents a comparison of a representative number of classical and swarm based protocols. Comparing routing protocols in WSNs is currently a very challenging task for protocol designers. Often, much time is required to re-create and re-...

Many cryptographic protocols are intended to coordinate state changes among principals. Exchange protocols coordinate delivery of new values to the participants, e.g. additions to the set of values they possess. An exchange protocol is fair if it ensures that delivery of new values is balanced: If one participant obtains a new possession via the protocol, then all other participants will, too. Fair exchange requires progress assumptions, unlike some other protocol properties. The strand space model is a framework for design and verification of cryptographic protocols. A strand is a local behavior of a single principal in a single session of a protocol. A bundle is a partially ordered global execution built from protocol strands and adversary activities. The strand space model needs two additions for fair exchange protocols. First, we regard the state as a multiset of facts, and we allow strands to cause changes in this state via multiset rewriting. Second, progress assumptions stipulate that some channels are...

The think-aloud protocol, also known as concurrent verbalisation protocol, is widely used in the field of HCI today, but as the technology and applications have evolved the protocol has had to cope with this. Therefore new variations of the protocol have seen the light of day. One example is retrospective verbalisation. To compare concurrent and retrospective verbalisation an experiment was conducted. A home healthcare application was evaluated with 15 participants using both protocols. The results of the experiment show that the two protocols have each their strengths and weaknesses, and as such are very equally good although very different.

In this paper, we present a new protocol for optimistic rollback recovery in distributed systems. This protocol is completely asynchronous, minimizes rollback, and is independent of any particular underlying distributed computation to be made fault tolerant. This protocol improves on earlier work in asynchronous optimistic rollback recovery in that previous protocols either sacrificed some of these properties or required larger timestamps. Furthermore, we establish that this protocol is optimal, in that no rollback recovery protocol can achieve these properties and have asymptotically smaller timestamps.

A group key exchange (GKE) protocol allows a group of parties communicating over a public network to establish a common secret key. As group-oriented applications gain popularity over the Internet, a number of GKE protocols have been suggested to provide those applications with a secure multicast channel. In this work, we investigate the security of Wu and Zhu's password-authenticated GKE protocol presented recently in FC'08. Wu and Zhu's protocol is efficient, supports dynamic groups, and can be constructed generically from any password-authenticated 2-party key exchange protocol. However, despite its attractive features, the Wu-Zhu protocol should not be adopted in its present form. Due to a flaw in its design, the Wu-Zhu protocol fails to achieve authenticated key exchange. We here report this security problem with the Wu-Zhu protocol and show how to solve it.   

We consider two-party quantum protocols starting with a transmission of some random BB84 qubits followed by classical messages. We show a general "compiler" improving the security of such protocols: if the original protocol is secure against an "almost honest" adversary, then the compiled protocol is secure against an arbitrary computationally bounded (quantum) adversary. The compilation preserves the number of qubits sent and the number of rounds up to a constant factor. The compiler also preserves security in the bounded-quantum-storage model (BQSM), so if the original protocol was BQSM-secure, the compiled protocol can only be broken by an adversary who has large quantum memory and large computing power. This is in contrast to known BQSM-secure protocols, where security breaks down completely if the adversary has larger quantum memory than expected. We show how our technique can be applied to quantum identification and oblivious transfer protocols.

... of the questions is, "What is the current protocol for screening the donor heart?" There's a number ... giving the right immunosuppressant medications. And usually the protocol after transplantation, it varies from center to center. ...

...review and discuss selected human gene transfer protocols and related data management...review and discuss selected human gene transfer protocols and related data management...NIH has instituted stringent procedures for entrance onto the NIH...

Volume III: Radiometric Measurements and Data Analysis Methods (Rev. 4) ... Detailed protocols for HPLC measurement of phytoplankton .... A simple “effective radius” adaptation of the GD protocol for MOBY and MOS ...............................5 ...

This report is a generic verification protocol by which EPA?s Environmental Technology Verification program tests newly developed equipment for distributed generation of electric power, usually micro-turbine generators and internal combustion engine generators. The protocol will ...

In-network data aggregation is an essential technique in mission critical wireless sensor networks (WSNs) for achieving effective transmission and hence better power conservation. Common security protocols for aggregated WSNs are either hop-by-hop or end-to-end, each of which has its own encryption schemes considering different security primitives. End-to-end encrypted data aggregation protocols introduce maximum data secrecy with in-efficient data aggregation and more vulnerability to active attacks, while hop-by-hop data aggregation protocols introduce maximum data integrity with efficient data aggregation and more vulnerability to passive attacks. In this paper, we propose a secure aggregation protocol for aggregated WSNs deployed in hostile environments in which dual attack modes are present. Our proposed protocol is a blend of flexible data aggregation as in hop-by-hop protocols and optimal data confidentiality as in end-to-end protocols. Our protocol introduces an efficient $O(1)$ heuristic for checking...

Stove testing is important and necessary. Lab tests provide valuable information, but are inadequate for predicting field performance. Field tests are needed, including controlled cooking test protocols and kitchen performance test protocols. The objectiv...

Leukemia; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Lymphoma; Sexual Dysfunction and Infertility; Sexuality and Reproductive Issues; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Key words: Firewalls, grids, high performance networking, multiport protocols, network ... same models are just as applicable to modern protocols for grids, high performance file transfer, voice over ...... Vsftpd. http://vsftpd.beasts.org. 38. Welch ...

This document explains how to integrate the TESLA source authentication and packet integrity protocol to the ALC and NORM content delivery protocols. This document only considers the authentication/integrity of the packets generated by the session's sender.

...Reports/System Access Application; OMB 3220-0008...Transfer Protocol (FTP), secure Email or...includes RRB Form BA-12, Application for Employer Reporting...Transfer Protocol (FTP), or secure Email...Notice of Employees' Applications and Claims for...

In 2009, Tseng et al. proposed a password sharing and chaotic map based key agreement protocol (Tseng et al.'s protocol). They claimed that the protocol provided mutual authentication between a server and a user, and allowed the user to anonymously interact with the server to establish a shared session key. However, in 2011, Niu et al. have proved that Tseng et al.'s protocol cannot guarantee user anonymity and protocol security when there is an internal adversary who is a legitimate user. Also it cannot provide perfect forward secrecy. Then Niu et al. introduced a trust third party (TTP) into their protocol designing (Niu et al.'s protocol). But according to our research, Niu et al.'s protocol is found to have several unsatisfactory drawbacks. Based on reconsidering Tseng et al.'s protoco...

This protocol describes how to genotype mice using Quantitative Polymerase Chain Reaction (PCR). The protocol focuses specifically on Ts65Dn mice, but can be used as a basis for genotyping ohter strains.

Long-term monitoring of hydrologic change using a standard data-collection protocol is essential for the effective management of terrestrial, aquatic, and estuarine ecosystems in the coastal park environment. This study develops a consistent protocol for ...

The main aim of the quantum cryptography protocols is the maximal secrecy under the conditions of the real experiment. This work presents the result of the new protocol building with the use of the secrecy maximization. While using some well known approaches this method has allowed to achieve the completely new results in quantum cryptography. The process of the protocol elaboration develops from the standard BB84 protocol upgrading to the building of completely new protocol with arbitrary large bases number. The secrecy proofs of the elaborated protocol appear to be natural continuation of the protocol building process. This approach reveals possibility to reach extremely high parameters of the protocol. It suits both the restrictions of contemporary technologies and requirements for high...

The Digital Imaging and Communications in Medicine (DICOM) Standard specifies a non-proprietary data interchange protocol, digital image format, and file structure for biomedical images and image-related information. The fundamental concepts of the DICOM message protocol, services, and informat...

The introduction of multislice computed tomography (MSCT) has provided the thoracic radiologist with a powerful tool with which to image the lungs. Enthusiasm for new protocols should be tempered with concerns over the potential increase in radiation dose, and before older protocols are abandoned there should be good evidence that newer protocols are objectively superior. Ultimately, the best protocol is one that provides the most relevant clinical information at the lowest dose possible.

An improved protocol for thermogravimetric analysis (TGA) of samples of single-wall carbon nanotube (SWCNT) material has been developed to increase the degree of consistency among results so that meaningful comparisons can be made among different samples. This improved TGA protocol is suitable for incorporation into the protocol for characterization of carbon nanotube material. In most cases, TGA of carbon nanotube materials is performed in gas mixtures that contain oxygen at various concentrations. The improved protocol is summarized.

Key-exchange protocols have been overlooked as a possible means for implementing oblivious transfer (OT). In this paper we present a protocol for mutual exchange of secrets, 1-out-of-2 OT and coin flipping similar to Diffie-Hellman protocol using the idea of obliviously exchanging encryption keys. Since, Diffie-Hellman scheme is widely used, our protocol may provide a useful alternative to the conventional methods for implementation of oblivious transfer and a useful primitive in building larger cryptographic schemes.

As stated in the Request for Proposal, a clinical protocol document shall be provided with the technical proposal. This “Protocol Document Template” presents the recommended format and required content for the clinical protocol document. During the competitive source selection those Offerors in the competitive range may be asked to respond to questions from the DCP Technical Evaluation Panel to improve and strengthen their proposal and to make the corresponding changes in the protocol document.

This thesis-project aims to research the possibilities of new wireless technologies in general control-situations. We have studied different existing control protocols, and developed a new protocol focusing on textbased menus. Our protocol is scaleable, easy to implement, and platform- and media ind...

We review a communication protocol recently proposed by us that makes use of a two-way quantum channel. We provide a characterization of such a protocol from a practical perspective, and consider the most relevant eavesdropping strategies against it. This allows us to compare its potentialities with those of a standard protocol which uses a one-way quantum channel.

This paper introduces the doubly-linked list (DLL) protocol for distributed shared memory (DSM) multiprocessor systems. The protocol makes use of two linked lists to keep track of valid copies of pages in the system, thus eliminating the use of copysets. Simulation studies show that the DLL protocol...

In this research report, we present simulation results for the Optimized Link State Routing protocol: «OLSR». «OLSR» is a routing protocol currently submitted at the IETF in the Mobile Ad-hoc NETwork workgroup. «OLSR» is a proactive protocol, thus it periodically sends «control» packets to build and...

SYNC2SINK is a global synchronization protocol used for Wireless Sensor Net-work. The objective of this thesis is to implement SYNC2SINK protocol on the CC2510-based data gathering sensor network and mastering the radio interface.The project consists of two parts: framework design and protocol imple...