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  • 1
    ISSN: 1432-0851
    Keywords: TNFα ; TNFβ ; sTNF-RI ; sTNF-RII ; Bladder cancer ; BCG immunotherapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Intravesical immunotherapy for bladder cancer is the most effective form of tumour immunotherapy. Following repeated instillations of bacillus Calmette-Guerin (BCG) organisms into the bladder large quantities of several cytokines are detected in the urine. These cytokines include interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor α(TNFα), interferon γ(IFNγ) and also soluble intercellular adhesion molecule ICAM-1. In the work reported here we simultaneously quantified urinary levels of TNFα, TNFβ, TNF receptor I and TNF receptor II by enzyme-linked immunosorbent assay (ELISA) techniques and compared this with bioactive levels of TNF. This was undertaken with a limited number of patients throughout a course of six instillations of immunotherapy. Sequential instillations of BCG induced secretion of TNFα and TNFβ into urine. These cytokines were not always secreted simultaneously, perhaps suggesting differential regulation of their synthesis. Maximal concentrations of TNFα were 675 pg/ml and TNFβ 47 pg/ml. High levels of both species of soluble TNF receptor were readily identified in urine. Maximal levels of sTNF-RI were 6200 pg/ml (range from 0) and for sTNF-RII 7800 pg/ml (range from 0). Contrasting with earlier published observations concerning cytokine levels, the concentration of soluble receptor did not increase with repeated instillation. In apparent contrast with the ELISA data, very low levels of bioactive TNF were identified by the L929 bioassay (maximum concentration 1 U/ml) despite the elevated concentration of immunoreactive TNF. The large concentrations of soluble TNF receptor in patients' urine samples could account for the apparently low bioactivity as determined by the L929 cytotoxicity assay. The precise nature of the role of TNF in BCG immunotherapy remains undetermined; however, it is thought that proinflammatory cytokines are in part responsible for the clinical efficacy of this therapeutic approach. Whether other cytokines are antogonised by soluble binding proteins remains to be determined. Furthermore, whether TNF is bioactive in the bladder wall and only neutralised in the urine also requires investigation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Annals of biomedical engineering 14 (1986), S. 401-415 
    ISSN: 1573-9686
    Keywords: Linear-lumped-parameter modeling ; Parameter optimization ; Frequency dependence ; Airway wall compliance ; Lung mechanics ; Comparative respiratory mechanics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Technology
    Notes: Abstract Pulmonary impedance, ZL, measured from 2 to 32 Hz in anesthetized, intubated and paralyzed bonnet monkeys (Macaca radiata) was fitted to a variety of linearlumped parameter mechanical networks. Parameter values for each network were obtained by minimizing the average of the percent distance, Dr, between the computed network impedance and measured ZL at all frequencies. Measured resistance, RL, decreased from 2 to 8 Hz and increased from 8 to 32 Hz indicating that a single series resistance-inertance-compliance (RIC) network was not optimal (Dr∼19%). Networks consisting of two series RIC pathways in parallel resulted in a lower Dr (∼14%), but parameter values were difficult to interpret. Despite not modeling the decrease in RL with frequency below 8 Hz, an airway wall compliance, C aw , network in which the airways were separated into central and peripheral components resulted in an even lower Dr (∼11%). In addition, parameter values were easy to interpret, consistent among our “normal” monkeys and changed consistently and explainably with change in lung mechanics induced by decrease in lung volume. We conclude that (1) networks containing both parallel pathways and C aw are necessary to model ZL over the entire frequency range (2–32 Hz), (2) the effect of C aw is an important determinant of ZL above 8 Hz, and (3) a six-parameter C aw network with the ratio of C aw to parenchymal compliance, Cp, fixed may prove useful in interpreting changes in ZL induced by alterations in lung mechanics in monkeys.
    Type of Medium: Electronic Resource
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