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  • Cell & Developmental Biology  (2)
  • GBS toxin  (2)
  • brightness  (1)
  • 1
    ISSN: 1572-817X
    Keywords: brightness ; efficiency ; electroluminescence ; organic diode
    Source: Springer Online Journal Archives 1860-2000
    Topics: Electrical Engineering, Measurement and Control Technology , Physics
    Notes: Abstract Remarkable improvement in efficiency and electroluminescence (EL) has been observed in an organic EL device, which consists of a hole-transport layer and a luminescent layer. The hole-transport layer is an N,N′-bis(3-methyphenyl)-N,N′-diphenylbenzidine film. The doped emitting layer consists of 8-(quinolinolate)-aluminum as the host and rubrene as the emission dopant. The doped cell with aluminum cathode demonstrated a luminance in excess of 20,000 cd/m2 and an external quantum efficiency of 2.7%, which is about four times and three times, respectively, greater than those of the undoped cell. The EL emission from the device shows spectral narrowing and a shift to higher energy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1335
    Keywords: CM101 ; GBS toxin ; Cancer ; Inflammation ; Neovascularization ; Angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A polysaccharide toxin, GBS toxin, is produced by group BStreptococcus (GBS) isolates from neonates who died of “early-onset disease”. GBS toxin, named CM101 in the clinic, was hypothesized, on the basis of our previous in vivo studies, to induce inflammation in pulmonary neovasculature in neonates by crosslinking of embryonic receptors still expressed after birth and in tumor neovasculature in adults. Immunohistochemical in vitro analysis of human biopsies showed that tumor neovasculature is indeed a binding site for CM101. In vivo studies in mice have demonstrated that CM101 induced inflammatory responses in neoplastic tumor neovasculature causing inhibition of tumor growth and tumor cell necrosis. These experimental observations warranted a phase I clinical trial for CM101 as an anti-neovascularization agent in human cancer therapy. Cancer patients received one cycle of therapy consisting of three treatments during 1 week. CM101 was administered over 15 min by i.v. infusion. Dosages of 7.5 μg/kg (1 U/kg),n=3; 15 μg/kg (2 U/kg),n=6; 24.75 μg/kg (3.3 U/kg),n=3; and 37.5 μg/kg (5 U/kg),n=3 were used. Enzyme-linked immunosorbent sandwich assays (ELISA) of the patients' sera showed a marked elevation of soluble E-selectin with a peak concentration observed at 8–12 h after each CM101. infusion. The average baseline value for soluble E-selectin prior to the first treatment was 97.3±23.4 ng/ml (mean±SEM,n=15) and the average peak level at 8 h was 441.6±62.4 (mean±SEM,n=15;P〈0.001). Subsequent treatments gave average maximum soluble E-selectin levels again at 8 h of 466.9±87.6 and 412.0±67.8 ng/ml, for treatment 2 and 3 respectively. Baseline values for treatment 2 and 3 were 192.3±26.4 and 226.4±26.1 ng/ml respectively (p〈0.01 versus treatment 1). Out of 15 patients, 5 showed tumor reduction or stabilization and were given additional cycles of therapy. CM101 induced an increase in soluble E-selectin levels, which remained elevated over baseline at the start of the following treatment cycles. The baseline remained elevated for several weeks after the final treatment, i.e.,P〈0.01 for levels before treatment 1 compared to those at week 4 after treatment. Elevated soluble E-selectin is considered proof of endothelial engagement in an inflammatory process. Our data support the contention that the inflammatory response observed in these cancer patients is targeting the tumor neovasculature and that measurement of soluble E-selectin levels in patients treated with CM101 can provide important information on the magnitude of CM101-mediated neovascular endothelial activation and tumor cell damage in cancer of endothelial origin, or cancer with a major neo-angiogenic component.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1335
    Keywords: Key words CM101 ; GBS toxin ; Cancer ; Inflammation ; Neovascularization ; Angiogenesis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A polysaccharide toxin, GBS toxin, is produced by group B Streptococcus (GBS) isolates from neonates who died of “early-onset disease”. GBS toxin, named CM101 in the clinic, was hypothesized, on the basis of our previous in vivo studies, to induce inflammation in pulmonary neovasculature in neonates by crosslinking of embryonic receptors still expressed after birth and in tumor neovasculature in adults. Immunohisto chemical in vitro analysis of human biopsies showed that tumor neovasculature is indeed a binding site for CM101. In vivo studies in mice have demonstrated that CM101 induced inflammatory responses in neoplastic tumor neovasculature causing inhibition of tumor growth and tumor cell necrosis. These experimental observations warranted a phase I clinical trial for CM101 as an anti-neovascularization agent in human cancer therapy. Cancer patients received one cycle of therapy consisting of three treatments during 1 week. CM101 was administered over 15 min by i.v. infusion. Dosages of 7.5 μg/kg (1 U/kg), n=3; 15 μg/kg (2 U/kg), n=6; 24.75 μg/kg (3.3 U/kg), n=3; and 37.5 μg/kg (5 U/kg), n=3 were used. Enzyme-linked immunosorbent sandwich assays (ELISA) of the patients’ sera showed a marked elevation of soluble E-selectin with a peak concentration observed at 8–12 h after each CM101 infusion. The average baseline value for soluble E-selectin prior to the first treatment was 97.3±23.4 ng/ml (mean±SEM, n=15) and the average peak level at 8 h was 441.6±62.4 (mean±SEM, n=15; P〈0.001). Subsequent treatments gave average maximum soluble E-selectin levels again at 8 h of 466.9±87.6 and 412.0±67.8 ng/ml, for treatments 2 and 3 respectively. Baseline values for treatments 2 and 3 were 192.3±26.4 and 226.4±26.1 ng/ml respectively (p〈0.01 versus treatment 1). Out of 15 patients, 5 showed tumor reduction or stabilization and were given additional cycles of therapy. CM101 induced an increase in soluble E-selectin levels, which remained elevated over baseline at the start of the following treatment cycles. The baseline remained elevated for several weeks after the final treatment, i.e., P〈0.01 for levels before treatment 1 compared to those at week 4 after treatment. Elevated soluble E-selectin is considered proof of endothelial engagement in an inflammatory process. Our data support the contention that the inflammatory response observed in these cancer patients is targeting the tumor neovasculature and that measurement of soluble E-selectin levels in patients treated with CM101 can provide important information on the magnitude of CM101-mediated neovascular endothelial activation and tumor cell damage in cancer of endothelial origin, or cancer with a major neo-angiogenic component.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 147 (1991), S. 374-382 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: Insulin was observed to modulate the growth and the phosphoenolpyruvate carboxykinase(PEPCK) activity of primary cultures of rabbit renal proximal tubule cells in serum free medium. Insulin was stimulatory to primary proximal tubule cell growth at a concentration of 10-8 M. In contrast, insulin was inhibitory to a proximal tubule function, PEPCK activity, following a 5-minute incubation period. An insulin dosage as low as 10-10 M was inhibitory to PEPCK activity, suggesting the involvement of insulin receptors. Although insulin was required at a significantly higher dosage to stimulate the growth of the primary renal proximal, tubule cells than to inhibit PEPCK activity, the elevated dosage required in order to observe a growth effect may be explained by the degradation of insulin by the primary renal proximal tubule cells. However the possible involvement of receptors for Insulin-like Growth Factor I (IGF-I) and Insulin-like Growth Factor II (IGF-II) in mediating the effects of insulin cannot be excluded. Other effector molecules were also examined with respect to their effects on PEPCK activity. The possible involvement of cyclic AMP in the control of the PEPCK activity of the primary renal cells was indicated by the stimulatory effects of 8 bromocyclic AMP, isobutyl methylxanthine (a cyclic AMP phosphodiesterase inhibitor), and forskolin (an activator of adenylate cyclase). Phorbol 12-myristate 13-acetate (TPA), which activates protein kinase C, was inhibitory. The actions of these effector molecules and insulin on the PEPCK activity of the primary renal cultures are remarkably similar to their effects on hepatic PEPCK. Several growth factors, fibroblast growth factor (FGF), and transforming growth factor beta (TGF beta) were also examined. FGF was observed to be stimulatory, whereas TCF beta was inhibitory to the PEPCK activity of the primary renal proximal tubule cells.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Journal of Cellular Physiology 151 (1992), S. 337-346 
    ISSN: 0021-9541
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The role of PGE1 in regulating the activity of the Na+, K+ -ATPase in Madin Darby Canine Kidney (MDCK) cells has been examined. PGE1 increased the initial rate of ouabain-sensitive Rb+ uptake by MDCK cells, a process that continued to occur over a 5-day period The increase in the initial rate of ouabain-sensitive Rb+ uptake in MDCK cells treated with PGE1 could be explained by a 1.6-fold increase in the Vmax for ouabain-sensitive Rb+ uptake. The increase in the Vmax for ouabain-sensitive Rb+ uptake observed in MDCK cells under these conditions can be explained either by an increase in the number of active Na+ pumps, or by an increase in the efficiency of the Na+ pumps. Consistent with the former possibility is the observed increase in the number of ouabain binding sites, as well as the increase in Na+, K+-ATPase activity in cell lysates obtained from MDCK monolayers treated with PGE1. The involvement of cyclic AMP in mediating these effects of PGE1 on the Na+, K+-ATPase in MDCK cells is supported by: (1) the observation of similar effects in 8-bromocyclic AMP treated MDCK monolayts, and (2) a dramatic reduction of the stimulatory effects of PGE1 and 8-bromocyclic AMP on the Vmax for ouabain-sensitive Rb+ uptake, and on the number of ouabain binding sites in dibutyryl cyclic AMP resistant clone 3 (DBr 3) (which is defective in cyclic AMP dependent protein kinase activity). PGE1 independent MDCK monolayers exhibit both an increase in the Vmax for ouabain-sensitive Rb+ uptake and an increase in the number of ouabain binding sites in response to 8-bromocyclic AMP. Apparently, the cyclic AMP phosphodiesterase defect in these PGE1 independent cells did not cause cellular cyclic AMP levels to be elevated to a sufficient extent to maximally increase the Na+, K+-ATPase activity in these variant cells. © 1992 Wiley-Liss, Inc.
    Additional Material: 4 Ill.
    Type of Medium: Electronic Resource
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