Optimizing the efficiency of ECAP measurements due to interpolation.

Background: Thresholds of electrically evoked compound action potentials (TECAP) may serve as starting points for electrophysiologically based fitting of cochlear implants. Absent TECAP data at single electrodes reduces the number of data points available for fitting and can be substituted by interpolation of measured data points.

Aim: To compare complete TECAP profiles with interpolated TECAP profiles of 5/22 (∼22.

Speech comprehension across multiple CI processor generations: Scene dependent signal processing.

Objectives: In clinical practice, characterization of speech comprehension for cochlear implant (CI) patients is typically administered by a set of suprathreshold measurements in quiet and in noise. This study investigates speech comprehension of the three most recent cochlear implant sound processors; CP810, CP910, and CP1000 (Cochlear Limited). To compare sound processor performance across generations and input dynamic range changes, the state-of-the art signal processing technologies available in each sound processor were enabled.

ECAP analysis in cochlear implant patients as a function of patient's age and electrode-design.

Introduction: Electric compound action potentials (ECAPs) provide information about the nerve's and device's function in and after cochlear implantation. In general, lower ECAP values are expected to generate better results. Aim was an analysis of ECAPs in the course of time as a function of the patient's age and electrode design.

Antitumor activity of the R- and S-enantiomers of RS-2-[[hydroxy[[2-[ (octadecyloxy)methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N, N,N,-trimethylethylaminium hydroxide inner salt.

The R- and S-enantiomers of 2-[[hydroxyl[[2-[(octadecyloxy) methyl]tetrahydrofuran-2-yl]methoxy]-phosphinyl]oxy]-N,N,N,- trimethylethylaminium hydroxide salt (SRI 62-834) have been evaluated in several assays to determine potential antitumor activity. The S-enantiomer showed slightly greater cytotoxic activity than the R- or RS-forms against several murine tumor cell lines. In the mouse Meth A fibrosarcoma model, the S-enantiomer was ca.

Preclinical pharmacology and possible mechanism of action of the novel antitumor agent 5-(4'-piperidinomethylphenyl)-2,3-dihydroimidazo [2,1-a]isoquinoline.

SDZ 62-434 (CAS 115621-95-9, 5-(4'-piperidinomethylphenyl)-2,3-dihydroimidazo [2,1-a]isoquinoline dihydrochloride), a member of a novel class of antitumor agents, exhibited direct and macrophage-induced cytotoxicity against a variety of murine tumor cell lines. It is more effective than edelfosine in increasing survivors and reducing tumor volume in the oral mouse Meth A fibrosarcoma model. Preliminary studies suggest that an undefined cytotoxic effect, macrophage activation and possible effects on signal transduction may account for its antitumor mechanism of action.

Antitumor activity of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines.

A series of 5-aryl-2,3-dihydroimidazo[2,1-a]isoquinolines previously reported to be platelet activating factor (PAF) receptor antagonists were evaluated for potential antitumor activity. Several compounds, such as the 5-(4'-tert-butylphenyl) (65), 5-[4'-(trimethylsilyl)phenyl] (69), and 5-(4'-cyclohexylphenyl) (71) analogs showed very good cytotoxicity against several tumor cell lines. 5-[4'-(Piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1- a]isoquinoline (SDZ 62-434, 53) was more effective on a milligram per kilogram basis than the clinical cytostatic agent edelfosine (1) in increasing survivors and decreasing tumor volume in the oral mouse Meth A fibrosarcoma assay.

Antitumor activity of a piperidine phospholipid.

A piperidine phospholipid ((+/-)-2-[hydroxy] [1-octadecyloxycarbonylpiperidin-3-yl]methoxy-phosphinyl] oxy]-N,N,N, trimethylethaniminium hydroxide inner salt, SDZ 62-826) has been prepared that exhibited weak direct cytotoxicity and strong macrophage-induced cytotoxicity in vitro against a variety of murine and one human tumor cell lines. This compound was found to be as effective as ET-18-OCH3 and SRI 62-834, phospholipids with both strong direct and macrophage-induced cytotoxicity, in increasing survivors and reducing tumor volume when given either orally or intravenously in the mouse MethA fibrosarcoma model. These findings suggest that the macrophage-induced cytotoxicity exhibited by ET-18-OCH3 and other phospholipids may play an important role in this tumor model.

Macrophage mediated tumor cell destruction measured by an alkaline phosphatase assay.

A new assay to measure the cytotoxic or growth-inhibitory activity of macrophages against tumor cells is described. The method is based on the fact that, in contrast to macrophages, natural killer cells or cytotoxic lymphocytes, a variety of tumor cells have a very high content of alkaline phosphatase. The strong linearity between tumor cell number and alkaline phosphatase activity in the cultures permits evaluation of macrophage function with standard ELISA equipment.

Age-related changes in interleukin production in BALB/cNNia and SJL/J mice and their modification after administration of foreign macromolecules.

In vitro production of Interleukin-2, -3, -4 and -10 by activated lymphocytes of BALB/cNNia and SJL/J was studied. While IL-2 production in BALB/c mice remains constant throughout the life span of the animals (8-113 weeks), an increase in production from stimulated SJL cells was seen. Age-related increases in IL-3 and IL-4 production occur between young and middle age (8-60 weeks) in both strains.

Differential modulation of the effects of lipopolysaccharide on macrophages by a major outer membrane protein of Proteus mirabilis.

We previously showed that a major protein isolated from purified cell walls of Proteus mirabilis (39-kDa protein) is a strong modulator of the specific immune responses to LPS from this bacterium in mice. When mixed with LPS before immunization, this protein enhances T cell-dependent, IgG antibody-producing cell responses specific for LPS. Furthermore, complexes of the 39-kDa protein with LPS drastically inhibit the production of oxygen radicals by murine macrophages activated with LPS, as measured in a chemiluminescence assay.

Alkyllysophospholipid prevents induction of experimental allergic encephalomyelitis.

Alkyllysophospholipids are synthetic analogues of natural phospholipids possessing a high immunomodulating and antitumoral capacity. Experimental autoimmune encephalomyelitis is a model disease for multiple sclerosis which can be induced by injecting rats with myelin basic protein, MBP. The effect of one alkyllysophospholipid, ET-18-OCH3, on the course of experimental autoimmune encephalomyelitis was investigated.

Antitumor activity of Ilmofosine (BM 41.440) in the 3Lewis-lung carcinoma model.

Ilmofosine (1-hexadecylthio-2-methoxymethyl-1,3-propanediol-phosphocholine, BM 41.440) is a thioether phospholipid with cytostatic/cytotoxic properties. The antineoplastic activity of this compound was investigated in vivo in the 3Lewis-lung carcinoma system.

Cyclic oxygen analogues of alkyl-lysophospholipids. Synthesis and neoplastic cell growth inhibitory properties.

Ether phospholipids have demonstrated both in vitro and in vivo activity against a wide variety of tumor cell lines. The known cyclic ether phospholipid, SRI 62-834, was used as the model to prepare eight novel phospholipids containing a cyclic ether. All of the compounds were as effective as ET-18-OCH3 in their ability to activate macrophage-induced cytotoxicity against the Abelson-8.

Influence of platelet activating factor and a nonmetabolizable analogue on superoxide production by bone marrow derived macrophages.

Serum-free cultured macrophages could be stimulated for lucigenin-dependent chemiluminescence by platelet activating factor (PAF) and phorbol myristate acetate (PMA). Stimulation with PMA resulted in a desensitization against PAF, whereas prestimulation with PAF had no influence on a following response caused by PMA. The PAF analogue, 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (Et-18-OCH3), did not induce chemiluminescence by itself and desensitized the cells against PAF, like substimulating concentrations of PAF.

Increased membrane permeability for an antitumoral alkyl lysophospholipid in sensitive tumor cells.

We have investigated cellular sensitivity to the antitumoral alkyl lysophospholipid (ALP) 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine (ET-18-OCH3) in vitro. The permeation of this lipid into the cell was not influenced by metabolic inhibitors of ATP biosynthesis. ET-18-OCH3 uptake was not saturable within sublytic concentrations, but could be inhibited in part by cytochalasin B (CB) and dipyridamole.

[Determination of the phagocytosis of granulocytes by the measurement of chemiluminescence].

During two successive years the phagocytic capacity of the granulocytes of 800 children from areas with environmental pollution and with clean air was examined and compared. To this end, the luminol chemiluminescence during phagocytosis of opsonized zymosan was measured in whole blood. In all areas the phagocytic activity of the granulocytes of boys was higher than that of girls.

Antitumor activity of SRI 62-834, a cyclic ether analog of ET-18-OCH3.

SRI 62-834, an analog of the antitumor agent ET-18-OCH3 in which the oxygen atom at carbon atom 2 has been incorporated into a five-membered heterocycle, has been prepared and evaluated as an antitumor agent. The compound exhibited good cytotoxicity in vitro against a variety of tumor cell lines and was as effective as ET-18-OCH3 given orally in the mouse Meth A sarcoma model. SRI 62-834 was shown to be an inhibitor of platelet-derived growth factor (PDGF), possibly at the receptor level, and platelet-activating factor (PAF) at the receptor level.

Ether phospholipids as inhibitors of the arachidonoyl-CoA: 1-acyl-sn-glycero-3-phosphocholine acyltransferase in macrophages.

1-Alkylglycerophosphatide analogs which are known to activate macrophages to enhanced tumor cytotoxicity are structurally closely related to 1-acyl-sn-glycero-3-phosphocholine. In this study we have examined the influence of some of these compounds and of platelet-activating factor (PAF-acether, 1-0-alkyl-2-0-acetyl-sn-glycero-3-phosphocholine) on the arachidonoyl-CoA: 1-acyl-sn-glycero-3-phosphocholine acyltransferase (EC 2.3.

Effect of a lysolecithin analogue on nonspecific resistance to infection of mice.

The effect of racemic 1-octadecyl-2-methoxy-sn-glycero-3 phosphorylcholine (ET-18-OCH3) on the nonspecific resistance of mice to infection with Salmonella typhimurium was investigated. Two S. typhimurium strains with different virulence were studied and no effect was observed in either case at concentrations of ET-18-OCH3 up to 100 micrograms/mouse.

Tumor cytotoxicity of human macrophages after incubation with synthetic analogues of 2-lysophosphatidylcholine.

Human alveolar macrophages as well as macrophages derived from Teflon culture of blood-borne monocytes were incubated with synthetic analogues of 2-lysophosphatidylcholine and then tested for their cytotoxic capacity against an allogeneic lymphoma cell line. Metabolic, rather stable analogues enhanced macrophage cytotoxicity significantly. This phenomenon was shown both in a growth-inhibition assay as well as in the 51Cr release assay.

Influence of the alkyllysophospholipid ET-18-OCH3 on methylnitrosourea-induced rat mammary carcinomas.

This study describes the efficacy of the alkyllysophospholipid 1-octadecyl-2-methoxy-Sn-racglycero-3-phosphocholine (ET-18-OCH3) in inhibiting the growth of methylnitrosourea-induced mammary carcinomas in Sprague-Dawley rats. In experiment A 2 X 10 mg/kg Et-18-OCH3 were administered daily for 10 weeks prior to manifestation of mammary carcinomas which resulted in a significant inhibition of median tumor number and median tumor volume per rat. Treatment of established tumors (experiment B) with 6 and 60 mg/kg ET-18-OCH3 daily for 3 weeks effected a stagnation in tumor growth for the higher dosage only with 90% tumor inhibition in comparison to untreated controls; at the same time, however, clear toxic effects were seen, thus indicating a narrow therapeutic index of ET-18-OCH3 in single-drug therapy.

Temperature dependence of leukemic cell destruction by alkyl-lysophospholipids (NSC 324368).

Alkyl-analogs (ALP) of 2-lysophosphatidylcholine induce a progressive destruction of neoplastic cells by interfering with the continuous turnover of membrane phospholipids. Using leukemic blast cells from patients with acute forms of leukemia the effect of temperature was evaluated. It was found that temperature strongly influences the cytotoxic activity of ALP.

Cell-destructive activity in the serum of a tumor patient after infusion of alkyl lysophospholipid.

Sera collected from 1 tumor patient after a 12-hour infusion of 30-50 mg alkyl lysophospholipids (ALP)/kg induced a progressive destruction of human leukemia cells (HL60) in vitro. This cytotoxic serum activity correlated with the dose of ALP administered and was inhibited by the addition of a metabolizable lysophospholipid analogue. Human bone marrow cells and concanavalin A-stimulated lymphoblasts were affected to a much lesser degree, whereas cells of the erythroleukemia line K562 appeared to be relatively resistant.