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Biomedical subjects

G Stark

Publications and source records attributed to G Stark.

At least 145 records · Page 8Linked to original sources

[Surgical therapy of stage Ib cervix cancer].

The following question was to be resolved: In view of the usually only minimal involvement (7.9%) of the parametria in stage Ib cervical cancer (CC Ib), is their complete removal necessary in such cases? Experience has shown that exposure can lead to subsequent impairment of the ureter, the bladder, and the rectum. Consequently, between 1971 and 1979, CC Ib was treated surgically in an alternating pattern: either after Wertheim-Meigs (WM) (108 cases in all), or after Galvin-TeLinde (GT), that is to say, with retention of the parametria to a large extent (102 cases in all). Results of histological study of the surgical specimens revealed approximately the same material in the two groups. Postoperative irradiation was performed in approximately 50% of the patients in both groups. In both groups, the frequency of metastases and recurrence was around 20%. In 1983, the evaluation of all the cases revealed a survival rate of 72.3% in the WM group, and of 78.5% in the GT group. The frequency of fistula and complaints in the GT group was only about one third of the found in the WM group. From their investigations, the authors conclude that the parametria do not have to be removed completely in cases of CC Ib, since late results are just as good with this limited operation as with Wertheim-Meigs' radical operation, yet with fewer complications. The removal of the affected uterus together with the pelvic lymph nodes and the extirpation of a vaginal cuff should be obligatory.

Combined Modality Therapy↗

Effects of ionizing radiation on artificial (planar) lipid membranes. I. Radiation inactivation of the ion channel gramicidin A.

The ion channel formed by the pentadecapeptide gramicidin A in planar lipid membranes is extremely sensitive to ionizing radiation. The membrane conductance may drop by several orders of magnitude under appropriate experimental conditions (low pH and presence of oxygen). The radiation sensitivity is strongly reduced for gramicidin M-. This analogue has the four tryptophan residues replaced by phenylalanines. Experiments performed in the presence of various radical scavengers suggest that the inactivation of the channel is due to a combined action of OH and of HO2 radicals at the tryptophan residues. The shape of the inactivation curves following continuous radiolysis or pulse radiolysis were found to be in fair agreement with a simple model which assumes that the damage of a single tryptophan residue is sufficient for channel inactivation. The conductance of inactivated channels could not be resolved within the experimental accuracy. This is contrary to photolysis of gramicidin channels found by Busath and Waldbilling (1983), where a broad distribution of low conductance states was observed. The inactivation by radiolysis seems to represent an 'all-or-none-process' of the channel conductance.

Dose-Response Relationship, Radiation↗

Effect of ionizing radiation on artificial (planar) lipid membranes. II. The ion carriers valinomycin and nonactin as probes for radiation induced structural changes of the membrane.

Planar lipid membranes in the presence of the ion carriers valinomycin or nonactin were irradiated with 14 MeV electrons from a linear accelerator. A large increase of the membrane conductance by up to more than two orders of magnitude was found. The effect is virtually abolished either at high pH, or in the absence of oxygen, or in the presence of the radical scavenger ethanol. A further prerequisite for the effect is the presence of unsaturated fatty acid residues. A kinetic analysis of the carrier transport model based on current-voltage curves and on voltage-jump relaxation experiments was performed as a function of radiation dose. Only the translocation rate constant, kMS, of the charged carrier-ion complex was found to be influenced by irradiation. The effect is interpreted as an increase of the polarity (dielectric constant) of the membrane interior induced by the presence of polar products of lipid peroxidation. A combined action of OH- and HO2-radicals seems to be responsible for the phenomena. At large radiation doses (greater than or equal to 10(3) Gy) a reduction of the membrane conductance was observed. This is interpreted as an increased microviscosity, possibly caused by cross-linking of fatty acid residues. Ion carriers represent sensitive probes of radiation induced membrane damage.

Anti-Bacterial Agents↗

Temperature-jump and voltage-jump experiments at planar lipid membranes support an aggregational (micellar) model of the gramicidin A ion channel.

The kinetics of formation and dissociation of channels formed by gramicidin A and two analogues in planar lipid membranes was studied using a laser temperature-jump technique developed earlier [Brock, W., Stark, G., Jordan, P.C. (1981), Biophys. Chem. 13:329-348]. The time course of the electric current was found to agree with a single exponential term plus a linear drift. In case of gramicidin A the relaxation time was identical to that reported for V-jump experiments [Bamberg, E., Läuger, P. (1973), J. Membrane Biol. 11:177-194], which were interpreted on the basis of a dimerization reaction. The same results were obtained for gramicidin A and for chemically dimerized malonyl-bis-desformylgramicidin. It is therefore suggested that the dimerization represents a parallel association of two dimers to a tetramer. There is evidence that the tetramer, contrary to the presently favored dimer hypothesis, is the smallest conductance unit of an active gramicidin channel. An additional V-jump-induced relaxation process of considerably larger time constant is interpreted as a further aggregation of gramicidin dimers.

Electric Conductivity↗

A laser-temperature-jump method for the study of the rate of transfer of hydrophobic ions and carriers across the interface of thin lipid membranes.

The first application of a laser-temperature-jump apparatus for the study of ion transport through planar (artificial) lipid membranes is described. The relaxation of the electric current is detected, either continuously at a constant applied voltage or discontinuously by a series of short voltage pulses. The second technique, a combined voltage- and temperature-jump method, is especially appropriate to investigate the kinetics of the adsorption/desorption process of hydrophobic ions and neutral carriers of cations at the membrane interface and to separate this phenomenon from the diffusion process through the unstirred aqueous layers adjacent to the membrane. The aim is to determine the rate-limiting step of transport. The permeation rate of the hydrophobic anion 2,4,6-trinitrophenolate is limited by the inner membrane barrier. For tetraphenylberate the rate constant of translocation across the inner barrier and that of desorption from the membrane into water are found to be of comparable magnitude. The membrane permeability of the neutral macrocyclic ion carrier enniatin B is strongly interface limited by its comparatively small rate of desorption into water. These results show that the frequently used a priori assumption of partition equilibrium at the membrane interfaces during transport is not justified.

Journal Article↗

Negative hydrophobic ions as transport-mediators for positive ions: evidence for a carrier mechanism.

The permeability of hydrophobic cations, such as tetraphenylarsonium across biological membranes and artificial lipid membranes is strongly increased in the presence of trace amounts of hydrophobic anions like tetraphenylborate (Liberman, Y.A. and Topaly, V.P. (1969) Biofizika 14, 452--461). Voltage-jump relaxation experiments performed on thin lipid membranes support the idea that the anions, A-, act as carriers for the cations, B+, by the formation of neutral ion pairs, A-B+. Their permeability is not affected by the electric dipole potential, which hinders the movement of free cations, B+.

Anions↗

Marble brain disease: recessive osteopetrosis, renal tubular acidosis and cerebral calcification in three Saudi Arabian families.

Four children are described from three Saudi Arabian families suffering from osteopetrosis, distal renal tubular acidosis and cerebral calcification associated clinically with mental retardation, stunted growth, abnormal teeth and a similar facial appearance. The syndrome is inherited as an autosomal recessive. The growth retardation is attributed to renal tubular acidosis but no metabolic link is evident between its other major features, and the fundamental defect is unknown. The disorder is radiologically indistinguishable from the classical recessive (malignant) and dominant (benign) forms of osteopetrosis but its other characteristics establish it as a separate disease entity.

Acidosis, Renal Tubular↗