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Biomedical subjects

I Thalmann

Publications and source records attributed to I Thalmann.

At least 55 records · Page 3Linked to original sources

Stimulus-induced release of endogenous amino acids from skins containing the lateral-line organ in Xenopus laevis.

The release of endogenous amino acids from skins of Xenopus laevis was studied by comparing the effects of pulsatile water motion on the efflux of glutamate and aspartate from isolated skins with and without lateral-line stitches. The stimulated efflux of glutamate from stitch skins was significantly greater than its stimulated efflux from non-stitch skins (p < 0.01). The results for aspartate were less clear cut. Although the source and mechanisms underlying the greater stimulated efflux from stitch skins remain to be determined, the results demonstrate that differences can be detected between stitch and non-stitch skins under stimulus conditions which should induce release of the afferent transmitter substance(s).

Animals↗

Organ of Corti-specific polypeptides: OCP-I and OCP-II.

Two polypeptides, OCP-I and OCP-II, specific to the organ of Corti of the quinea pig and the rate, were detected by two-dimensional polyacrylamide gel electrophoresis. They were neither present in other inner ear structures, nor in other organs tested. The two polypeptides constitute a substantial portion of the total protein of the organ of Corti. Both inner and outer layer of the organ of Corti contained approximately equal amounts of OCP-I and OCP-II. The molecular weights of OCP-I and OCP-II are 37,000 and 22,500 daltons, respectively. The corresponding pI values are 4.9 and 5.1, respectively. in addition, actin and tubulin were detected in both layers of the organ of Corti.

Animals↗

Maintenance of cochlear function with artificial oxygen carriers.

By means of vascular perfusion via the anterior inferior cerebellar artery with a blood substitute containing the perfluorochemical FC 47 as oxygen carrier, it is possible to maintain normal or near normal levels of the cochlear microphonics and the endolymphatic potential of the guinea pig for perios of 90 min, or longer. Following 60 min. of perfusion with artificial blood, the levels of ATP and 5' AMP in the stria vascularis and the organ of Corti are comparable to those of nonperfused control animals maintained at optimal metabolic conditions. Following the same period of perfusion, the appearance of the organ of Corti is normal, but small vacuoles, presumably deposits of FC 47, are visible in the marginal cells of the stria vascularis. Preliminary experiments concerning the survival time and the revival time of the cochlear potentials, as well as the response to furosemide, ouabain, and mersalyl are presented to illustrate the value of this method in elucidating various biochemical and pharmacological problems of the cochlea.

Adenosine Monophosphate↗

Adenine nucleotides of the stria vascularis.

The levels of the adenine nucleotides ATP, ADP, and AMP in the stria vascularis were measured under normal conditions, and following various durations of ischemia. The concentrations of these compounds were used for the calculation of the adenylate energy charge, the energy status and the phosphorylation state of the stria. Following 10 min of ischemia the adenylate energy charge had decreased three fold, the energy status seven fold and the phosphorylation state 14 fold. To study the potential for recovery of strial function following various brief and prolonged ischemic intervals, a method for the perfusion of the ear via the anterior inferior cerebellar artery was developed. For various reasons it was found advantageous to use "artifical blood" as perfusate, relying upon fluorocarbons as oxygen carriers. The endolymphatic potential was used as electrical indicator of strial function. Recovery of the endolymphatic potential following brief periods of ischemia was paralleled by a corresponding increase of the ATP levels and a drastic decrease of the AMP levels of the stria vascularis. Preliminary results on the effects of substrate-free perfusion are presented.

Adenine Nucleotides↗

Adenylate energy charge, energy status, and phosphorylation state of stria vascularis under metabolic stress.

The purpose of the reported experiments was to measure the strial concentrations of adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) in order to arrive at estimates of three commonly used adenylate ratios. Under normal conditions, the concentrations of ATP, ADP, and AMP were found to be 11.4, 3.7, and 0.6 mmoles/kg dry weight, respectively. Of the three substances, AMP is the most sensitive indicator of metabolic stress, since its concentration doubles within 6 sec. of ischemia and reaches a peak level of about 1500% of the control following 65 sec. of ischemia. Under normal conditions, the "adenylate energy charge," the "energy status," and the "phosphorylation state" amount to 0.84, 3.0, and 1.52 gram wet weight/mumole, respectively. In ischemia of 10 min. duration, the adenylate energy charge decreases 3 fold, the energy status 7 fold and the phosphorylation state 14 fold. The size of the adenylate pool shows a slight increase in the earliest stage of ischemia, but declines progressively thereafter. The apparent equilibrium constant of strial adenylate kinase was found to be 0.48. The advantages and limitations of the different adenylate ratios, as indicators of metabolic health and as regulatory parameters, are discussed.

Adenosine Diphosphate↗

Noxious effects upon cochlear metabolism.

The influence of various toxic substances and of drugs with ototoxic side effects upon energy generation, energy utilization, and membrane processes of the cochlea were studied. None of the drugs tested interfered with energy generation to as great an extent as did anoxia or cyanide and 2,4-dinitrophenol. Ouabain produced a pronounced interference with energy utilization of the stria vascularis. The "loop" diuretics ethacrynic acid and furosemide produced a reduction of energy utilization of a lesser degree than did ouabain. The "loop" diuretics do not seem to exert their toxic action upon strial Na+K+-ATPase, but may act by interfering with strial adenylate cyclase. Aminoglycoside antibiotics and diuretic and nondiuretic mercurials seem to exert their primary noxious action upon cochlear function by interfering with membrane processes of the structures bounding the cochlear duct.

Action Potentials↗

Cyclic AMP and adenylate cyclase in the inner ear.

The activity of adenylate cyclase and the steady state levels of cyclic AMP (cAMP) were determined in stria vascularis (SV) and organ of Corti (OC) of the guinea pig cochlea. The activities are 12 and 19 pmoles/mg dry weight/minute for OC and SV, respectively. The activity was increased two to four-fold by NaF. The base level of cAMP is 4.2 and 4.4 nmoles/g dry weight in OC and SV, respectively. In contrast to brain, neither ischemia nor barbiturates produced major changes of the steady state levels of cAMP. No in vitro effect of cAMP upon the state of activation of glycogen phosphorylase was noticeable in either tissue. cAMP did not exert a significant in vitro inhibition of strial Na+K+-ATPase. Perilymphatic perfusion of cAMP (10-3 M) and of theophylline (5 times 10-3 M) did not produce changes in the endolymphatic potential (EP), but dibutyryl cAMP (10-3 M) led to a significant increase of EP. The alpha adrenergic blocking agent, phentolamine, produced very complex changes of the cochlear potentials. A possible role of catecholamines and cAMP in the secretory phenomena of the SV and in the transduction and/or transmission processes of the auditory sense organ are discussed.

Action Potentials↗

Otosclerosis: a local manifestation of a generalized connective tissue disorder?

The hypothesis that otosclerosis is a local manifestation of a clinically and genetically heterogeneous group of generalized connective tissue disorders was tested by quantitative biochemical techniques. In contrast to previous studies, no significant differences were found in individual glycosaminoglycans excreted in urine of control subjects and patients with otosclerosis. Moreover, no significant differences were detected in the rate of synthesis and secretion of glycosaminoglycans and collagen in skin fibroblast cultures of patients and controls. Preliminary results obtained with more sensitive and specific methods suggest a possible error in collagen metabolism. Polyacrylamide gel electrophoresis revealed slight differences in migration patterns of several collagenous proteins between patients and control subjects. In addition, collagenase was significantly increased in three of five patients.

Cells, Cultured↗

Distribution of cyclic nucleotides in the organ of Corti.

Recent developments in radioimmunoassay technology have made possible measurements of cyclic nucleotides in individual specimens of the organ of Corti and its subdivisions. Steep longitudinal and transverse gradients of glycogen are known to exist in the organ of Corti of the guinea pig, with preferential accumulation in the outer hair cells of the apical turns. However, no significant longitudinal gradient of cyclic AMP was detectable in the organ of Corti, and the concentration of the compound was found to be nearly equal in the inner and outer hair cell layers. This is indirect evidence against the concept that cyclic AMP plays a role as "second messenger" in the control of glycogen metabolism of the organ of Corti. By contrast, the concentration of cyclic GMP was found to be consistently higher in the inner layer than in the outer layer of the organ of Corti, and to increase significantly in basal direction. This trend is remarkably similar to the distribution patterns of acetylcholinesterase, which may be considered as indirect evidence in favor of a possible role of cyclic GMP in the mediation of cholinergic effects.

Acetylcholinesterase↗