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  • 1
    Keywords: APOPTOSIS ; PROTEIN-KINASE ; MICROTUBULES ; EPITHELIAL-CELLS ; vimentin ; PHOSPHORYLATION SITES ; CULTURED FIBROBLASTS ; DYNAMIC PROPERTIES ; NEUROFILAMENT PROTEIN ; PERIPHERIN
    Abstract: Withaferin A (WFA) is a steroidal lactone present in Withania somnifera which has been shown in vitro to bind to the intermediate filament protein, vimentin. Based upon its affinity for vimentin, it has been proposed that WFA can be used as an anti-tumor agent to target metastatic cells which up-regulate vimentin expression. We show that WFA treatment of human fibroblasts rapidly reorganizes vimentin intermediate filaments (VIF) into a perinuclear aggregate. This reorganization is dose dependent and is accompanied by a change in cell shape, decreased motility and an increase in vimentin phosphorylation at serine-38. Furthermore, vimentin lacking cysteine-328, the proposed WFA binding site, remains sensitive to WFA demonstrating that this site is not required for its cellular effects. Using analytical ultracentrifugation, viscometry, electron microscopy and sedimentation assays we show that WFA has no effect on VIF assembly in vitro. Furthermore, WFA is not specific for vimentin as it disrupts the cellular organization and induces perinuclear aggregates of several other IF networks comprised of peripherin, neurofilament-triplet protein, and keratin. In cells co-expressing keratin IF and VIF, the former are significantly less sensitive to WFA with respect to inducing perinuclear aggregates. The organization of microtubules and actin/microfilaments is also affected by WFA. Microtubules become wavier and sparser and the number of stress fibers appears to increase. Following 24 hrs of exposure to doses of WFA that alter VIF organization and motility, cells undergo apoptosis. Lower doses of the drug do not kill cells but cause them to senesce. In light of our findings that WFA affects multiple IF systems, which are expressed in many tissues of the body, caution is warranted in its use as an anti-cancer agent, since it may have debilitating organism-wide effects.
    Type of Publication: Journal article published
    PubMed ID: 22720028
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  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Food Chemistry 47 (1993), S. 11-15 
    ISSN: 0308-8146
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0003-9861
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1423-0127
    Keywords: Common allergenic epitope ; Minor allergen ; Bermuda grass pollen ; Cyn dI ; Lol pI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The present study disclosed the cross-reactivity between Bermuda grass pollen (BGP) and other grass pollens using monoclonal antibodies (MAbs) and polyclonal antiserum. MAb 9–13, directed against a group of minor allergens of BGP (Cyn d Bd68K, 48K, 38K) was found to cross-react with extracts of ten other grass pollens. Immunoblotting assays illustrated that MAb 9–13 cross-reacted with multiple components of most of these pollens, and the major cross-reactive components had molecular weights of 29–36 kD. The cross-reactivity between BGP andLol pI, the group I allergen of rye grass pollen, was further evaluated;Lol pI was recognized by MAb 9–13, but not by our MAbs/polyclonal antiserum againstCyn dI, the major allergen of BGP. These results suggest that the epitope recognized by MAb 9–13 is a common (C) epitope shared byLol pI andCyn d Bd68K, 48K, 38K, andCyn dI does not share significant antigenicity withLol pI. In a modified radio-allergosorbent test, IgE antibodies in the serum of BGP-allergic patients reacted mildly with C-epitope-bearing components of both BGP and rye grass pollens, and this binding could be blocked specifically by MAb 9–13. This suggests that in addition to an antigenic cross-reaction, the C epitope can also lead to an allergenic cross-reaction.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0012-1606
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1434-3916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Arthroscopy of the knee joint was performed in 356 consecutive outpatients in local anaesthesia and without premedication. A continuous pressure-irrigation system was used with 0.2% lidocaine chloride solution in the irrigation fluid, following administration of 5–7 ml prilocaine with epinephrine in each portal. All patients had clinical symptoms of internal derangement of the knee, such as meniscal, cruciate ligament injury or osteoarthritis. Associated intra-articular pathology was registered. Intra-articular surgery was performed in 228 cases. This included partial or subtotal meniscectomy in 207 cases and meniscus suture in 3 cases. In 18 of 228 cases (8%) the operative procedure had to be terminated due to patient discomfort. Of the meniscal injuries 84% were medial and 16% lateral. The age distribution of the medial meniscus tears was as follows: bucket handles 33 ± 9 years; flap tears 42 ± 10 years and degenerative tears 53 ± 10 years. For the lateral meniscus the age distribution was: bucket handles 34 ± 9 years, cleavage and radiating tears 37.5 ± 12 years, flap tears 29 ± 7 years, peripheral tears 32 ± 9 years and degenerative tears 48 ± 11 years. Osteoarthritis was observed in 52% of all medial degenerative tears, whereas a low frequency was found in the remaining tears. The majority of patients tolerated the procedure well. In summary, 64% of the consecutive arthroscopies were operative, including 3 meniscal sutures. Only 8% of these procedures had to be abandoned due to patient discomfort. Thus, arthroscopic surgery in local anaesthesia with no premedication is an efficient and well-tolerated method in outpatient practice.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1434-3916
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This report describes the incidence, localization, and cause of injuries in Swedish male and female elite gymnasts during 18 active months (three seasons). Thirty-one elite gymnast clubs with all together 437 gymnasts were included in the study, which consisted of a written questionnaire reporting morphometric facts as well as data concerning the injury. There were in total 82 injury reports. The injury incidence was 6.25 per 100 elite gymnasts and season. A majority of the injuries occurred in the lower extremities. The right leg was injured more often than the left. Most of the severe injuries occurred during mounting and dismounting which advocates the need for preventive measures in association with these particular events. Male gymnasts were more prone to sustain severer injuries such as dislocations and fractures. Severe injuries affected the upper extremity in 83%, and the right side was injured more often than the left.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1614-3116
    Keywords: creep damage ; visco-elasticity ; finite element method ; short fibre composite ; computer simulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract Creep damage at crack tip in short fibre composites has been simulated by using the finite element method (FEM). The well-known Schapery non-linear viscoelastic constitutive relationship was used to characterize time-dependent behaviour of the material. A modified recurrence equation was adopted to accelerate the iteration. Kachanov-Rabotnov's damage evolution law was employed. The growth of the damage zone with time around the crack tip was calculated and the results were shown with the so-called “digit photo”, which was produced by the printer.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1600-0838
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Sports Science
    Notes: We recently presented a pilot study using an instrumented staple system for measurein in vivo local deformation on tibia. Methodological development has now proceeded in vitro. Consecutively, we performed 1. a sheep bone micrometer study, 2. a sheep bone four-point bending test and 3. a pig bone four-point and three-point bending test. This was done in order to secure a standardized application of the staple, to analyze the interaction of the bone and the staple and to secure calibration and reliability of the system to be used in vivo. With refernce to the above studies: 1. There was a linear relationship (r=0.998) between the applied deformation of the bone and the measured deformation of the staple. ICC values ranged from 0.866 to 0.997. 2. An excellent intra-test reliability as well as linearity between staple measures and surface strain on the bone was observed (r=0.998). 3. The slope of regression lines (k) was min 7.2 and max 9.4. The results from this test are used for calibration of the instrumented staple. Great variations were found between tension and compression measurements. However, within each test the SD was negligible. We suggest that the instrumented staple system may be calibrated in vitro and validly used for in vivo measurement of local bone deformation.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1546-1696
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: [Auszug] Accumulation of foreign proteins as inclusion bodies in Escherichia coli was investigated using single–cell light scatter measurements from flow cytometry. Significant increases in forward–angle light scatter and right–angle light scatter were observed for E. coli strains ...
    Type of Medium: Electronic Resource
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