Biomedical subjects

T Pröbstle

Publications and source records attributed to T Pröbstle.

3 recordsLinked to original sources

PubMed1998

Immunization with virus-modified tumor cells.

Direct infection of tumor cells with viruses transfering protective or therapeutic genes-a frequently used procedure for production of tumor vaccines in human gene therapy-is often limited by the number of tumor cells that can reliably be infected, as well as by issues of selectivity and safety. In this review, we describe an efficient, selective, and safe way of infecting human tumor cells with a natural virus with interesting pleiotropic immune stimulatory properties, the avian paramyxovirus Newcastle disease virus (NDV). Advantages of this virus are its good cell-binding properties, its selective replication in tumor cell cytoplasm, which is independent of cell proliferation, and its relative safety. Most important for its use as an adjuvant in human cancer vaccine are its ability to introduce T-cell costimulatory activity, to prevent anergy induction, and to induce locally chemokines (eg, RANTES, IP-10) and cytokines (eg, interferon alpha, beta [IFN-alpha, beta] and tumor necrosis factor-alpha [TNFalpha]) that affect T-cell recruitment and activation. A further development consists of attachment-via NDV-derived hemagluttinin-neuraminidase (HN) membrane-anchoring molecules-of universal defined bispecific reagents such as T-cell-activating anti-CD28 antibodies. Finally, we summarize the status of our clinical studies with the autologous virus modified live cell vaccine (ATV)-NDV.

Animals↗

PubMed1991

The different use dependences of tocainide and benzocaine are correlated with different effects on sodium channel inactivation.

To study the mechanism of use dependence, we investigated the influence of 0.5 mM tocainide on the amplitude of sodium currents elicited by membrane depolarizations with standard test pulses in voltage-clamped human myoballs. For comparison, the experiments were also conducted with 1 mM benzocaine, a drug with almost no use dependence. These concentrations were so chosen that without stimulation and at a holding potential of -135 mV, either drug blocked about 50% of the channels (tonic block). With repetitive stimulation at 1 Hz, tocainide blocked about 75% of the channels that had remained open in the rested state (phasic block), while benzocaine had little such effect. The potential dependence of steady-state inactivation (h infinity curves) of the sodium channels in these myoballs depended on the duration of the prepotential indicating that they possess at least two states of inactivation: fast and intermediate. The two drugs differed in their effects on these two states. Benzocaine always produced a left-shift of the h infinity curve, no matter whether the duration of the conditioning pulse was short (8 ms) or long (512 ms) indicating that it can bind when the channel is in the state of fast inactivation. Tocainide shifted the h infinity curve only with long prepulses, i.e. when the sodium channels were in the state of intermediate inactivation. The recovery from inactivation, a process governed by two time constants in the absence of drugs, was also differently influenced by the two drugs. In the presence of tocainide, the channels mainly recovered with the slow time constant and this time constant was significantly increased, whereas benzocaine did not substantially modify this biphasic process.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzocaine↗

PubMed1988

Hodgkin-Huxley parameters of the sodium channels in human myoballs.

Myoballs were cultured from biopsies of adult human skeletal muscle without the use of antimitotic drugs. The sodium currents flowing during stepwise depolarization of the myoball membrane were investigated with the wholecell recording technique. The temperature range covered 10-37 degrees C. Two types of sodium channel were distinguished by their different sensitivity to tetrodotoxin (TTX). The channel with normal TTX sensitivity seemed identical with the sodium channel in adult muscle, the channel with less TTX sensitivity seemed identical with the juvenile channel found in developing and in denervated muscle. The activation and inactivation parameters of both channel types were quantitatively determined. The activation parameters of the two channel types were identical, but in comparison to the h infinity-curve of the adult sodium channels the h infinity-curve of the juvenile channels was positioned at more negative potentials, had a less steep slope, and when the temperature was decreased, its point of inflection shifted more in negative direction.

Aged↗