Showing papers by "Free University of Berlin published in 1980"

Localization of short-term memory in the brain of the bee, Apis mellifera

Abstract: . Fixed honey-bees were conditioned to a scent in a one-trial learning paradigm. In contrast to free-flying colour-conditioned bees, fixed scent-conditioned bees do not show a biphasic time dependence of the conditioned response. Small metal probes were used to cool localized areas of the antennal lobes, alpha-lobes, and calyces of the mushroom bodies of the brain at various times after conditioning. Localized cooling impaired the formation of memory in all three structures. The susceptibility to impairment after conditioning lasted approximately 3 min in the antennal lobes, 7 min in the alpha-lobes, and 10 min in the calyx area. It was possible to determine the influence of the contralateral hemisphere (relative to the learning antenna) by conditioning bees with only one antenna. No contralateral impairment was found in the antennal lobes; there were minor effects in the alphalobes; contralateral cooling led to reductions of the conditioned response only in the calyx area. The temperature dependence of memory impairment was different for the antennal lobes and the mushroom bodies (alpha-lobes and calyces). The latter were most sensitive to cooling at 5°C. No correlation between cooling duration and impairment of memory was found in the antennal lobes, but there was a linear relation between impairment and cooling duration in the alpha-lobes. Brief cooling (5 or 10 s) resulted in significant impairment of memory formation only in the calyx area. A series of control experiments proved that the impairment of memory is due to a reversible block of neural activity. It was possible to show that the impairment is specific for the three neural structures analysed, by cooling the lobula of the optic system at various times after conditioning. Lesions of the brain or application of KCl also resulted in time-dependent reductions of the conditioned response. Cooling the entire animal at various times after conditioning led to similar memory impairment to that resulting from localized cooling of the alphalobes.

Molecular mechanisms involved in the production of cromosomal aberrations II. Utilization of neurospora endonuclease for the study of aberration production by X-rays in G1 and G2 stages of the cell cycle

Abstract: Chinese hamster ovary cells (CHO) were X-irradiated in G2 state of the cell cycle and immediately treated, in the presence of inactivated Sendai virus, with Neurospora endonuclease (E.C. 3.1.4.), an enzyme which is specific for cleaving single-stranded DNA. With this treatment, the frequencies of all types of chromosome aberrations increased when compared to X-irradiated controls. These results are interpreted as due to the conversion of some of the X-ray induced singe-stranded DNA breaks into double-strand breaks by this enzyme. Similar enhancement due to this enzyme was found following treatment with methyl methanesulfonate (MMS) and bleomycin, but not following UV and mitomycin C. Addition of Micrococcus endonuclease and Neurospora endonuclease to the cells did not alter the frequencies of aberrations induced by UV. The introduction of enzymes with specific DNA-repair function offers possibilities to probe into the molecular events involved in the formation of structural chromosome aberrations induced by different classes of physical and chemical mutagens.

Theoretical models for superionic conductors

Abstract: The present theoretical understanding of various properties of superionic conductors is reviewed. Emphasis is put on their treatment as classical many-particle systems and on the analysis of their dynamic behaviour. Different kinds of approaches pertaining to the low frequency dynamics are considered in detail. They include stochastic models, like hopping or Fokker-Planck models as well as a hydrodynamic theory. The high frequency (phonon-) dynamics and the information obtained from computer simulations is also analysed. As far as possible, the relevance of the different approaches with respect to experiments on specific materials is discussed. Possible directions for future investigations are outlined.

Effect of inhibitors of GABA transaminase on the synthesis, binding, uptake, and metabolism of GABA.

Abstract: Four catalytic inhibitors of GABA aminotransferase (gabaculine, γ-acetylenic GABA, γ-vinyl GABA, ethanolamine O-sulphate) as well as aminooxyacetic acid and valproate were studied for effects on neurochemical assays for GABA synthesis, receptor binding, uptake and metabolism in mouse and rat brain preparations. Gabaculine did not interfere with GABA synthesis as reflected by the activity of glutamate decarboxylase (GAD), it was only a weak inhibitor (IC50= 0.94 mM) of GABA receptor binding sites but was a moderately potent inhibitor of GABA uptake (IC50= 81 μM) and very potent (IC50= 1.8 μM) with respect to inhibition of the GABA-metabolizing enzyme GABA aminotransferase (GABA-T). γ-Acetylenic GABA was a weak inhibitor of GAD and GABA binding (IC50 > 1 mM), but virtually equipotent to inhibit uptake and metabolism of GABA (IC50 560 and 150 μM, respectively). This was very similar to γ-vinyl GABA, except that this drug did not decrease GAD activity. Ethanolamine O-sulphate was found to show virtually no inhibition of GAD and GABA uptake, but was a fairly potent inhibitor of GABA binding (IC50= 67 μM) and in this respect, 500 times more potent than as an inhibitor of GABA-T. Aminooxyacetic acid was a powerful inhibitor of both GAD and GABA-T (IC50 14 and 2.7 μM, respectively), but had very little affinity to receptor and uptake sites for GABA. Valproate showed no effects on GABA neurochemical assays which could be related to anticonvulsant action. The present results suggest that the anticonvulsant properties of the four catalytic inhibitors of GABA-T tested are at least in part mediated through a direct influence on GABA receptors and uptake sites.

The anchoring of glass ceramics of different solubility in the femur of the rat.

Abstract: A direct physicochemical bond between alkali-rich bioglass or glass ceramic (45 S 5 A and B, Hench) or alkali-poor glass ceramic (KG S, Bromer) and bone has been well documented. Since long-term studies have revealed the interface to be subjected to remodeling of the bone and to increased focal disintegration of the implant, glass ceramics of reduced solubility have been developed by lowering the Na2O content and adding Al2O3, Ta2O5, TiO2, and Sb2O3. Implants of glass ceramic KG S and different compositions with reduced solubility have been studied histologically 14, 29, or 30, 60, 119, and 245 days after implantation in the femur of male Sprague-Dawley rats. Implants of KG S are anchored at an interface with bone connection, which is known to provide for application of considerable shear and tensile strengths; whereas, at the interface of ceramics of reduced solubility, soft tissue, chondroid and osteoid are mainly observed. The dynamics of the events at the interface indicate a disturbance of the transformation of chondroid cells into osteoblasts and of the mineralization of osteoid. This disturbance of pathophysiologic processes during bone healing or bone regeneration is discussed.

1-Methyl-beta-carboline (harmane), a potent endogenous inhibitor of benzodiazepine receptor binding.

Abstract: The interaction of several beta-carbolines with specific [3H]-flunitrazepam binding to benzodiazepine receptors in rat brain membranes was investigated. Out of the investigated compounds, harmane and norharmane were the most potent inhibitors of specific [3H]-flunitrazepam binding, with IC50-values in the micromolar range. All other derivatives, including harmine, harmaline, and several tetrahydroderivatives were at least ten times less potent. Harmane has been previously found in rat brain and human urine, so it is the most potent endogenous inhibitor of specific [3H]-flunitrazepam binding known so far, with a several fold higher affinity for the benzodiazepine receptor than inosine and hypoxanthine. Thus, we suggest that harmane or other related beta-carbolines could be potential candidates as endogenous ligands of the benzodiazepine receptor.

Oral retinoids - present status.

Abstract: Oral retinoids are synthetic derivatives of vitamin A (retinol); they are potent and rather specific dermatotherapeutic drugs. Their development in the last 10 years and their clinical application has clearly introduced a new era in dermatotherapy. Skin diseases resistant to traditional local remedies, such as pustular psoriasis and Darier's disease and other keratotic genodermatoses, obviously respond to oral retinoid treatment. Additionally, since retinoids exert a particular pharmacological effect on skin and its appendages as a target tissue, their use in vitro and in animal experiments may help to increase our knowledge about the mechanisms of keratinization and epidermal growth control. Biosynthesis of new drugs often results from empirical knowledge of basic compounds, possibly of natural origin, indicating some beneficial properties in certain pathological conditions. In this case vitamin A was known to improve hyperkeratotic conditions in general, including acne; however, its therapeutic use was limited by its toxicity. Its therapeutic ratio, i.e. the relation between therapeutic dose and the lowest toxic dose, seemed inappropriate for long-term therapy in humans. Moreover, possible target tissues for serious side-effeas of the original vitamin A include non-keratinizing epithelia of the eyes and the gonads. In the late sixties and the following years extensive pilot studies with oral application of all-transretinoic acid, 13-cis-retinoic acid, all-trans-retinoic acid ethylamide and anhydroretinon acid were undertaken by our group, searching for a new effective compound for systemic treatment with a low incidence of\" side-effects. The overall results were rather moderate, particularly in psoriasis (Orfanos et al., 1972; Runne, Orfanos & Gartmarm, 1973). Similar to Schumacher & Stiittgen (1971) we found that the natural metabolite all-trans-retinoic acid was notably effective in disorders of keratinization and acne; however, in its therapeutic ratio it did not differ significantly from vitamin A. The daily dose required for treatment (50-200 mg) caused, as a rule, considerable side-effects. Anhydroretinon acid was less effective, retinoic acid ethylamide infiuenced Darier's disease (Orfanos, Kurka & Strunk, 1978a) and 13-cis-retinoic acid was found beneficial for acne and psoriasis at 50-100 mg/d; nevertheless, the frequency of its possible side-effects was still considered too high for it to be recommenced for routine therapy. After administration of retinoic acid ethylamide and 13-cis-retinoic acid in psoriasis elevation of blood sedimentation rate, transaminases, urea and serum lipid levels were noted (Runne et al., 1973). During these studies it became evident, however, that synthetic retinoids did maintain the basic efficacy of the parent compound, whereas some of the typical side-effects such as headaches, nausea and vomiting were less pronounced or rare; in low dosage their action was restricted mainly to keratinizing epithelia and their side-effects were dose-dependent and reversible.

Speech Acts in Interaction: A Critique of Searle.

Abstract: (1980). Speech acts in interaction: A critique of Searle. Discourse Processes: Vol. 3, No. 2, pp. 133-153.

Hospital admissions due to adverse drug reactions: A comparative study from Jerusalem and Berlin

Abstract: A comparative study of adverse drug reactions (ADR) leading to hospital admission showed that 103 (4.1%) out of 2499 medical admissions in Jerusalem and 167 (5.7%) out of 2933 admissions in Berlin were due to such reactions. Sex distribution in the two patient — populations was almost equal but the Jerusalem patients were younger. The most frequent ADRs were digitalis intoxication (in Berlin) and reactions to antibiotics (in Jerusalem). Other important differences were noted in the relative frequencies of ADRs associated anticoagulants, hypoglycemic agents and oral contraceptives. They were probably related to differences in drug usage in the two countries. The most common major side effects were arrhythmias, allergic reactions, bleeding, congestive heart failure, bronchospasm and hypoglycemia. The following risk factors were identified in both cities: old age, female sex, impaired renal function, previous history of ADR and polypragmasia.

The principle of electrical carotid sinus nerve stimulation: A nerve pacemaker system for angina pectoris and hypertension therapy

Abstract: Electrical carotid sinus nerve stimulation (CSNS) via an implanted electrode receiver assembly, radio frequency coupled to an external signal generator, is an experimental therapy for hypertension and angina pectoris. CSNS increases afferent information to the central nervous system exerting neurally regulated decreases in heart rate, stroke volume, and blood pressure. No nonspecific side effects are observed, in contrast to drug therapy. A nerve pacemaker system is described and compared to the commonly used open-loop stimulator system (fixed frequency and intensity CSNS). It is a closed-loop system, controlled by heart rate (as an indicator of the state of “arousal” and of sympathetic activity) and, thereby, feedback-controlled by its therapeutic effects. The miniaturized (hybrid technology) system consists of an ECG amplifier, a stimulus pattern memory with I-O periphery and a transmitter, including an antenna coil to be coupled to the implanted assembly. Stimulus parameters (frequency and amplitude of impulses) are optimized for each patient individually. Stimulus patterns (pulse synchronous amplitude modulated groups of impulses) are adapted to the patient's cardiovascular situation. The nerve pacemaker may be an alternative to drug therapy or major surgery in both diseases. Compatible with the open-loop system, it replaces the first step in previously treated CSNS patients.

Chromatic properties of identified interneurons in the optic lobes of the bee

Abstract: The properties of bee medulla and lobula neurons were investigated using intracellular recordings and light stimuli of different qualities. The intracellular injection of dye permitted the examination of the structure and position of neurons studied electrophysiologically. Examples of different coding mechanisms are given; transitional stages were also found.

Limited application period for dithranol in psoriasis. Preliminary report on penetration and clinical efficacy.

Abstract: SUMMARY This preliminary study suggests that a 1 h application of dithranol may be effective in the treatment of psoriasis. It is conceivable that short application periods for other topically applied agents, e. g. corticosteroids, may reduce the side-effects in non-affected skin, while maintaining the therapeutic benefit in diseased areas.

Principles of Percutaneous Absorption

Abstract: Skin is a highly differentiated, multi-functional and multi-layered organ and thus susceptible to a variety of different types of diseases. This has resulted in the development of a multitude of topical drugs, differing in their mode of action, their ability to penetrate into the skin and in the way the skin reacts to them.

A comparative study of the pharmacology of inhibitors of GABA-metabolism

Abstract: Four catalytic inhibitors of GABA-aminotransferase (GABA-T), viz. gabaculine, gamma-acetylenic GABA, gamma-vinyl GABA, and ethanolamine O-sulphate (EOS), as well as the unspecific enzyme inhibitor aminooxyacetic acid (AOAA), sodium valproate (VPA), and GABA itself were studied for anticonvulsant, biochemical, and toxic effects in mice. Elevations of the electroconvulsive threshold by 30 V were produced at the time of their maximal effect by the i.p. injection (AOAA s.c.) of 13 mg/kg AOAA, 37 mg/kg gabaculine, 65 mg/kg gamma-acetylenic GABA, 125 mg/kg VPA, 1,440 mg/kg EOS, 1,900 mg/kg gamma-vinyl GABA and 2,800 mg/kg GABA. At these doses, all drugs except GABA and VPA increased the clonic pentetrazole threshold to a similar extent, but differed in their increases in the brain content of GABA, which varied from 70% (EOS) to 300% (gamma vinyl GABA) as a consequence of decreases in the activity of GABA-T. The activity of the GABA-synthesizing enzyme glutamate decarboxylase was decreased only by gamma-acetylenic GABA. When determining the anticonvulsant effect of the different drugs against the convulsant ED 97 of pentetrazole, 3-mercaptopropionic acid, strychnine and maximal electroshock seizures, gabaculine, AOAA, VPA and in part gamma-vinyl GABA and GABA were efficacious enough to allow the determination of ED50 values, whereas gamma-acetylenic GABA and EOS showed no clear activity in any of these seizure models. Gabaculine and AOAA at their anticonvulsant ED50 were toxic or lethal. All inhibitors of GABA-T except EOS caused numerous side effects which cast doubt on the specificity of these drugs. The present results indicate that inhibitors of GABA-T hardly seem to be suited for treatment of convulsive disorders in human but are useful tools in studies of experimental epilepsy.

Chromosomal aberrations in peripheral lymphocytes of alcoholics.

Abstract: The frequencies of exchange-type aberrations found in peripheral lymphocytes of alcoholics were analysed in relation to age, sex, duration of alcohol dependency, treatment with antabuse and smoking habit. The statistical analyses were performed by the non-parametric Mann-Whitney U test and the Kruskal-Wallis 1-way analysis of vairance, both at a level of significance of P = 0.05. There was no dependency on age or sex. The chromatid exchange frequencies and the total of all exchanges were positively correlated with the duration of the dependency on alcohol and with smoking habit. Treatment with antabuse did not lead to an additional elevation of the frequency of exchange-type aberrations.

Health effects of traffic noise.

Abstract: In 57 test persons having worked 1 day under traffic noise (Leq = 85 dB(A) and 1 day without noise (Leq < 50 dB(A), blood pressure and pulse frequency were measured at 1 h intervals and total urine was collected during working hours. Additionally, blood was sampled at the end of each working day. Psychological parameters were assessed by means of questionnaires. Statistically significant reactions to noise were found in the following fields: 1. Ergnomics--decrease of working quality; 2. Psychology--increase of psychical tension; 3. Blood circulation--increase of blood pressure and pulse frequency; 4. Biochemistry--increase of epinephrine, cAMP, urine and serum Mg, protein, cholesterol plus decrease of erythrocyte Na, and renin. Hypothetical mechanisms of the action of traffic noise are discussed.

Display, Timing and Function of Wing Movements Accompanying Antiphonal Duets of Cichladusa Guttata

Abstract: I. The antiphonal duets of Cichladusa guttata (Turdidae, Aves) are often accompanied by spectacular wing movements. We have analysed the display, timing, coordination and function of this behaviour using sound films, audio and video recordings of free living and captured birds (Figs 1, 2). 2. The vocal duet contribution of the members of a pair appear well coordinated in timing, normally with no overlap of notes. Specific types of duet notes of the male or the female can release wing beats in the male (response time: 380 ± 80 msec.), but not vice versa. Additionally, note utterance can trigger the wing beat start (reaction time 30 ± 15 msec.) in the same bird, which is normally the male (Figs 4, 5, 6, 7, 8). 3. Wing beat performance is also affected by two further variables: "duet activity" and "wing beat periodicity". The duet activity which changes relatively slowly can be estimated from parameters of the behaviour (vocal density, vocal power, etc.). Auditory stimulation with conspecifics songs raises duet activity and thereby facilitates wing movements. This does not affect the "component of wing beat periodicity", which has a cycle length of 540 msec. (Fig. 3; Tab. i). 4. Normally, both wings are moved synchroneously. Experiments with restricted space on one side of a songster showed that wing beats can be blocked unilaterally. While a space restricted wing remained unmoved the other wing operated in full coordination to the duet program. 5. Due to the different affectations wing "escort" is optional. It occurs regularly, but, with high flexibility. When the variables promoting wing beats result in high values, high wing beats occur, when the values are low, low or no wing beats are observed (Fig. 9). 6. (Wing beats are supposed to support the general function described for the vocal duet contributions.) Specific functions discussed for the non-vocal contributions are: focussing and directing of attention (spectacular display via an additional signal channel; avoidance of habituation (optional and flexible occurrence) ; preventing distance signalling from disturbances in the acoustic channel (noise produced by birds singing simultaneously) ; distance measurement by identification of phase shifting between vocal and non-vocal behavioural rhythms.