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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Annals of oncology 10 (1999), S. 235-237 
    ISSN: 1569-8041
    Keywords: carboplatin ; metastatic nasopharyngeal carcinoma ; paclitaxel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: An earlier phase II trial of paclitaxel in patients with metastatic nasopharyngeal carcinoma (NPC) demonstrated a response rate of 22%. Hence we proceeded to study the combination of paclitaxel and carboplatin in these patients. Patients and methods: The 21-day regimen was as follows: i.v. paclitaxel 175 mg/m2 over three hours preceded by standard premedications, followed by i.v. carboplatin dosed at AUC of six infused over one hour. Only chemotherapy-naïve patients with histological diagnoses of undifferentiated carcinoma of the nasopharynx, systemic metastases and radiologically measurable lesions were eligible. Results: Thirty-two patients were accrued to this study. Twenty patients (62%) had at least two sites of metastasis. The main grade 3–4 toxicity was neutropenia (31%). Nine patients (28%) developed neutropenic sepsis, which caused the demise of one of them. Twenty-four patients (75%) responded to treatment, with one (3%) attaining a complete response. The median time to progression of disease was seven months and the median survival was 12 months. At one year, 52% of the patients were alive. Conclusions: The combination of paclitaxel and carboplatin is an active regimen in NPC. Its convenience of administration and good tolerability make it an attractive alternative regimen to consider for patients with metastatic disease.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Copenhagen : Munksgaard International Publishers
    Allergy 56 (2001), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background: Buckwheat flour (BF) is known as a potent food allergen. Sensitization to it usually occurs by ingestion but also by inhalation in occupational or domestic exposure. Buckwheat chaff-stuffed pillows (BCP) can be contaminated with BF during the process of pilling, and many Korean children and adults use BCP for health reasons. Methods and Results: We here present three cases of BF allergy in children using BCP, who had been treated as nonatopic asthmatics after undergoing the routine allergy skin tests and serologic tests. We took careful clinical histories, and performed skin prick tests (SPT), the radioimmunoassay (RIA) for specific IgE, the BCP-elimination test, the BF bronchial provocation test, and IgE Western blot. All three children showed positive skin reactions to BF, but none of them had positive reactions to house-dust mites. Nocturnal asthmatic symptoms were improved during 7 days of BCP elimination, and asthmatic responses were observed by bronchial provocation tests with homemade BF extract. Serum BF-specific IgE antibodies and several IgE-binding proteins were detected by RIA and Western blot analysis, respectively. Conclusions: Thus, a small amount of BF attached to BCP can induce BF sensitization, and BCP should be considered a main cause of childhood nocturnal asthma in those asthmatics exposed to these pillows.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Berlin, Germany : Blackwell Verlag GmbH
    ISSN: 1439-0264
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: cDNA of cyclin-dependent kinase 5 (Cdk5) was cloned based on its primary sequence homology to Cdc2 and Cdk2. Cdk5 requires the neuronal Cdk5 activators such as p35 or p39nck5ai (p39) for its activity. In this study, we examined post-natal changes in the p39 expression pattern during the development of the rat cerebellum. p39 began to express in somata and dendrites of Purkinje cells at post-natal day 3 (PD3). In particular, at PD12, parasagittal bands (stripes) with p39 immunoreactivity were weakly observed. At PD21, p39-immunoreactive stripes were developed when compared with the PD12 group. At this age stage, p39 immunoreactivity became weak in somata of Purkinje cells, not forming stripes. At PD28, a series of parasagittal bands were more distinct than those of the PD21 group, and p39 immunoreactivity disappeared in Purkinje cells, not forming p39 immunoreactive stripes. In the adults, p39 immunoreactivity in Purkinje cells was similar to that found in the PD28 group which showed that parasagittal bands were very narrow, and became progressively more slender. Therefore, we suggest that the post-natal changes of p39 expression in Purkinje cells in the cerebellum is an autonomous characteristic of Purkinje cells with a role of Cdk5 activators.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 67 (1990), S. 6360-6367 
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: Tunneling and thermionic emission through n+-GaAs–i-AlxGa1−xAs–n-GaAs heterojunction barriers are studied as a function of temperature from 77 to 200 K and as a function of externally applied uniaxial stress up to 10 kbar. A procedure to extract parameters for theoretical calculations is also proposed. The parameters extracted from the I-V characteristics of these heterostructures grown on (100) GaAs substrates with different aluminum mole fractions from 0.3 to 0.8 and thicknesses from 300 to 400 A(ring) agree well with those of previous reports. The dependence of the I-V characteristics on uniaxial stress in the 〈100〉 direction perpendicular to the heterojunction plane has also been measured. The experimental results show good agreement with theoretical calculations assuming there is a linear stress-dependent decrease of the energy-band edges of the longitudinal X valleys (Xl) in AlGaAs with respect to the Γ valley in GaAs. The slope of the decrease is found to be 14±2 meV/kbar. This results in an X-valley shear deformation potential of 9.6±1.8 eV, which is believed to be the most accurate measured value to date.
    Type of Medium: Electronic Resource
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  • 5
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    Unknown
    BMJ Publishing
    In: BMJ Open
    Publication Date: 2015-07-18
    Description: Objectives To assess the association between secondhand smoke exposure and blood lead and cadmium concentration in women in South Korea. Design Population-based cross-sectional study. Setting South Korea (Korea National Health and Nutrition Examination Survey V). Participants 1490 non-smoking women who took part in the fifth Korea National Health and Nutrition Examination Survey (2010–2012), in which blood levels of lead and cadmium were measured. Primary outcome measures The primary outcome was blood levels of lead and cadmium in accordance with the duration of secondhand smoke exposure. Results The adjusted mean level of blood cadmium in women who were never exposed to secondhand smoke was 1.21 (0.02) µg/L. Among women who were exposed less than 1 h/day, the mean cadmium level was 1.13 (0.03) µg/L, and for those exposed for more than 1 h, the mean level was 1.46 (0.06) µg/L. In particular, there was a significant association between duration of secondhand smoke exposure at the workplace and blood cadmium concentration. The adjusted mean level of blood cadmium concentration in the never exposed women's group was less than that in the 1 h and more exposed group, and the 1 h and more at workplace exposed group: 1.20, 1.24 and 1.50 µg/L, respectively. We could not find any association between lead concentration in the blood and secondhand smoke exposure status. Conclusions This study showed that exposure to secondhand smoke and blood cadmium levels are associated. Especially, there was a significant association at the workplace. Therefore, social and political efforts for reducing the exposure to secondhand smoke at the workplace are needed in order to promote a healthier working environment for women.
    Keywords: Open access, Addiction, General practice / Family practice, Health policy, Occupational and environmental medicine, Public health, Smoking and tobacco
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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  • 6
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    Unknown
    Oxford University Press
    Publication Date: 2015-05-29
    Description: HP0268 is a conserved, uncharacterized protein from Helicobacter pylori . Here, we determined the solution structure of HP0268 using three-dimensional nuclear magnetic resonance (NMR) spectroscopy, revealing that this protein is structurally most similar to a small MutS-related (SMR) domain that exhibits nicking endonuclease activity. We also demonstrated for the first time that HP0268 is a nicking endonuclease and a purine-specific ribonuclease through gel electrophoresis and fluorescence spectroscopy. The nuclease activities for DNA and RNA were maximally increased by Mn 2+ and Mg 2+ ions, respectively, and decreased by Cu 2+ ions. Using NMR chemical shift perturbations, the metal and nucleotide binding sites of HP0268 were determined to be spatially divided but close to each other. The lysine residues (Lys7, Lys11 and Lys43) are clustered and form the nucleotide binding site. Moreover, site-directed mutagenesis was used to define the catalytic active site of HP0268, revealing that this site contains two acidic residues, Asp50 and Glu54, in the metal binding site. The nucleotide binding and active sites are not conserved in the structural homologues of HP0268. This study will contribute to improving our understanding of the structure and functionality of a wide spectrum of nucleases.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 7
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    Unknown
    Oxford University Press
    Publication Date: 2012-05-13
    Description: VapD-like virulence-associated proteins have been found in many organisms, but little is known about this protein family including the 3D structure of these proteins. Recently, a relationship between the Cas2 family of ribonucleases associated with the CRISPR system of microbial immunity and VapD was suggested. Here, we show for the first time the structure of a member of the VapD family and present a relationship of VapD with Cas2 family and toxin–antitoxin (TA) systems. The crystal structure of HP0315 from Helicobacter pylori was solved at a resolution of 2.8 Å. The structure of HP0315, which has a modified ferredoxin-like fold, is very similar to that of the Cas2 family. Like Cas2 proteins, HP0315 shows endoribonuclease activity. HP0315-cleaved mRNA, mainly before A and G nucleotides preferentially, which means that HP0315 has purine-specific endoribonuclease activity. Mutagenesis studies of HP0315 revealed that D7, L13, S43 and D76 residues are important for RNase activity, in contrast, to the Cas2 family. HP0315 is arranged as an operon with HP0316, which was found to be an antitoxin-related protein. However, HP0315 is not a component of the TA system. Thus, HP0315 may be an evolutionary intermediate which does not belong to either the Cas2 family or TA system.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 14 (1997), S. 911-916 
    ISSN: 1573-904X
    Keywords: CTLA4Ig ; intravenous ; subcutaneous ; pharmacokinetics ; immunogenicity ; rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The objectives of this study were: to delineate the pharmacokinetics of CTLA4Ig in rats after single and multiple intravenous (IV) and subcutaneous (SC) doses; to assess the relationship of the pharmacokinetic parameters of CTLA4Ig vs dose; to calculate the SC absolute bioavailability; and to assess the antibody response of CTLA4Ig. Methods. A total of 48 (24 male and 24 female) Sprague Dawley rats were divided into eight treatments with 3 rats per gender in each group: a single dose of 10, 80, or 200 mg/kg of CTLA4Ig given either IV or SC and a repeated dose of 10 mg/kg (once every other day for 7 doses over 13 days) given either SC or IV. Serial blood samples were collected up to 43 days after single dose administration and up to 50 days following the administration of the last multiple dose on day 13. The serum concentration of CTLA4Ig and anti-CTLA4Ig antibodies were measured using ELISA assays. Results. After single IV doses, Cmax and AUCinf increased in a dose proportional manner; CL appeared to be dose independent, while both Vss and T1/2 increased as the administered dose increased. Following single SC doses, Cmax and AUCinf increased in a linear manner but not proportionally; mean Tmax values were prolonged but similar among the three dose levels, while T1/2 increased as the administered dose increased. The absolute SC bioavailability of CTLA4Ig decreased as the dose increased from 10 (62.5%), 80 (55.7%), and 200 mg/kg (41.1%). Comparison of the AUCtau values between the first and last doses suggested an accumulation (3.1−4.7) of CTLA4Ig. However, regardless of the route of dosing, AUCtau after the last dose were comparable to AUCinf values following the single dose. Anti-CTLA4Ig antibodies were detected at the 10 mg/kg dose level after single or multiple doses for both routes of administration. However, regardless of single or multiple doses, antibody titers were relatively greater for the SC compared to the IV administration. Conclusions. The key findings of this study were: (i) the elimination characteristics of CTLA4Ig were comparable between the SC and IV routes; (ii) the repeated dosing did not alter the pharmacokinetics of CTLA4Ig; (iii) the SC absolute bioavailability tended to decrease as the administered dose increased; and (iv) a greater formation of anti-CTLA4Ig antibodies was observed after SC compared to IV at a single 10 mg/kg dose level; however, after multiple dosing, the formation of antibodies from either of the two routes was relatively slower, and (v) during the study period, no antibodies were observed at either the 80 or 200 mg/kg dose levels regardless of the route of administration.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1573-7217
    Keywords: breast cancer ; cell cycle ; DNA-DMBA binding ; DNA repair ; DNA synthesis ; pathogenesis of breast cancer ; susceptibility to carcinogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been demonstrated that in humans certain factors such as early menarche, late pregnancy, and nulliparity are associated with a higher risk of developing breast cancer, while early pregnancy acts as a protective factor. Induction of mammary cancer in rats by administration of the chemical carcinogen 7, 12-dimethylbenz(a)anthracene reveals that the same factors influencing human breast cancer risk also affect the susceptibility of the rat mammary gland to the chemical carcinogen. Nulliparous rats and rats undergoing pregnancy interruption are more susceptible to developing carcinomas. This fact has been attributed to the incomplete differentiation of the gland at the time of carcinogen administration. Parous rats are resistant to the carcinogenic effect of DMBA, which is explained by the complete development of the gland attained during pregnancy and lactation. This development is manifested by the differentiation of terminal end buds into secretory units, which have a smaller proliferative compartment; the epithelial cells of these secretory units have a longer cell cycle, less avidity for binding DMBA, and possess a more efficient DNA excision repair capacity.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Biotechnology letters 14 (1992), S. 779-784 
    ISSN: 1573-6776
    Source: Springer Online Journal Archives 1860-2000
    Topics: Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary Pseudomonas elastase was found to be efficient in catalysing the reaction betweenN-benzyloxycarbonyl-L-aspartic acid and L-phenylalanine methyl ester producing the aspartame precursor in aqueous and aqueous methanolic solutions. 25% (v/v) methanol was most favourable for the synthesis where about 100% increase in yield was obtained compared to that in aqueous solution.
    Type of Medium: Electronic Resource
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