Search

Parathyroid hormone (PTH) increased intracellular cyclic AMP and reduces Na+/phosphate cotransport activity in OK cells [Malmström & Murer (1986) Am. J. Physiol. 251, C23-C31; Caverzasio, Rizzoli & Bonjour (1986) J. Biol. Chem. 261, 3233-3237]. It was also shown that PTH activates phosphoinositide metabolism in OK cells [Hruska, Moskowitz, Esprit, Civitelli, Westbrook & Huskey (1987) J. Clin. Invest. 79, 230-239]. In the present paper we show that tumour-promoting phorbol esters are effective in reducing Na+/phosphate cotransport. The Ca2+ ionophores A23187 and ionomycin had only a small effect on Na+/phosphate cotransport; added together, A23187 and phorbol esters showed a synergistic action. Phorbol esters and phorbol esters plus ionomycin stimulated prostaglandin synthesis as well as cyclic AMP production; acetylsalicylic acid prevented phorbol-ester-induced prostaglandin synthesis and cyclic AMP production, but had no effect on inhibition of Na+/phosphate cotransport. In suspensions of OK cells, PTH and thrombin produced a rise in intracellular Ca2+. In contrast with PTH, thrombin did not elevate cellular cyclic AMP in suspended OK cells. PTH and thrombin reduced Na+/phosphate cotransport in suspended OK cells. It is suggested that two regulatory cascades are involved in PTH action on Na+/phosphate cotransport: cyclic AMP/kinase A and Ca2+/diacylglycerol/kinase C.

Abstract.: In a previous report we documented an increased Na+-dependent transport of inorganic phosphate (P i ) in Xenopus laevis oocytes injected with mRNA isolated from rabbit duodenum (Yagci et al., Pfluegers Arch. 422:211–216, 1992; ref 24). In the present study we have used expression cloning in oocytes to search for the cDNA/mRNA involved in this effect. The identified cDNA (provisionally named PiUS; for P i -uptake stimulator) lead to a 3-4-fold stimulation of Na+-dependent P i -uptake (10ng cRNA injected, 3–5 days of expression). Na+-independent uptake of P i was also affected but transport of sulphate and l-arginine (in the presence or absence of sodium) remained unchanged. The apparent K m -values for the induced Na+-dependent uptake were 0.26 ± 0.04 mm for P i and 14.8 ± 3.0 mm for Na+. The 1796 bp cDNA codes for a protein of 425 amino acids. Hydropathy analysis suggests a lack of transmembrane segments. In vitro translation resulted in a protein of 60 kDa and provided no evidence of glycosylation. In Northern blots a mRNA of ∼2 kb was recognized in various tissues including different intestinal segments, kidney cortex, kidney medulla, liver and heart. Homology searches showed no similarity to proteins involved in membrane transport and its control. In conclusion, we have cloned from a rabbit small intestinal cDNA library a novel cDNA encoding a protein stimulating P i -uptake into Xenopus laevis oocytes, but which is not a P i -transporter itself.

The interaction between the moth, Cactoblastis cactorum, and the cactus, Opuntia stricta, is used as a model to examine the question of whether the CO2 sense of a herbivorous insect can detect the CO2 gradients associated with a plant's metabolic activity. Both the anatomical and the electrophysiological characteristics of CO2-sensitive receptor neurons in C. cactorum indicate an adaptation to the detection of small fluctuations around the atmospheric background. Evidence is provided that further rises in background will impair the function of the sensory organ. In the habitat of the plant, during the diurnal window of the moth's activity, two types of CO2 gradients occur that are detectable by the moth's sensors. The first gradient, associated with soil respiration, is vertical and extends from the soil surface to an altitude of approximately 1 m. Its magnitude is well above the detectability limit of the sensors. The notion that this gradient provides, to a flying insect, a cue for the maintenance of a flight altitude favourable for host detection is supported by field observations of behaviour. The second gradient, associated with CO2 fixation by the plant, extends from the surfaces of photosynthetic organs (cladodes) over a boundary layer distance of approximately 5 mm. Again, its magnitude is well above the detectability limit. The notion that this gradient provides, to a walking insect, a cue to the physiological condition of the plant is supported by the observation that females of C. cactorum, prior to oviposition, actively probe the plant surface with their CO2 sensors. In a simulation of probing, pronounced responses of the sensors to the CO2-fixing capacity of O. stricta are observed. We propose that by probing the boundary layer, females of C. cactorum can detect the healthiest, most active O. stricta cladodes, accounting for earlier observations that the most vigorous plants attract the greatest density of egg sticks.

Summary: Brush border membranes were isolated from rat renal cortex by a divalent cation precipitation method.l-35S-cysteine uptake into the vesicles was measured by a rapid filtration method. Only minimal binding of the amino acid to the vesicles was observed. Sodium stimulatesl-cysteine uptake specifically. Anion replacement experiments, experiments in the presence of potassium/valinomycin-induced diffusion potential as well as experiments with a potential-sensitive fluorescent dye document an electrogenic sodium-dependent uptake mechanism forl-cysteine. Tracer replacement experiments as well as the fluorescence experiments indicate a preferential transport ofl-cysteine. Transport ofl-cysteine is inhibited byl-alanine andl-phenylalanine but not byl-glutamic acid and thel-basic amino acids. Initial, linear influx kinetics provide evidence for the existence of two transport sites. The results suggest (a) sodium-dependent mechanism(s) forl-cysteine shared by other neutral amino acids.

Abstract: Brush border membranes were isolated from rat renal cortex by a divalent cation precipitation method.l-35S-cystine uptake into the vesicles was measured by a rapid filtration method. Covalent incorporation of tracer into membrane proteins was observed after prolonged incubations. At short incubation periods (1 min) binding was small and allowed an analysis of transmembrane transport. To guarantee transport ofl-cystine, the experiments were performed in the presence of the oxidant diamide.Sodium stimulatedl-cystine uptake specifically. A potassium/valinomycin induced inside negative diffusion potential stimulated sodium dependentl-cystine transport. Thus, transport is potential sensitive in the presence of sodium. At low substrate and inhibitor concentrations,l-cystine transport was inhibited byl-lysine,l-ornithine andl-arginine but not byd-lysine in the presence and absence of sodium. At higher inhibitor concentration, the neutral amino acidsl-phenylalanine andl-leucine also inhibitedl-cystine uptake, but only the sodium dependent uptake. These inhibition experiments suggest thatl-cystine is transported by the brush border membrane by a transport system for basic amino acids not necessarily requiring sodium. In addition, transport ofl-cystine can also procee via sodium dependent transport pathways for neutral amino acids.In the concentration range tested (up to 0.225 mmoles/l), no saturation ofl-cystine transport was observed in the presence and absence of sodium.

In a former investigation the effect of promethazine (Atosil®) on the late acoustically evoked potential component N1 was examined. Now the cochlear and the brain-stem potentials were registered by the earlobe-vertex pick-up with i.m. application of 0.8 mg/kg (body weight) promethazine. There was no influence of promethazine either on the compound action potential (NAP) or on the brain-stem potentials (Pot. II–V), but sedation improves significantly the signal-to-noise ratio, therefore we sedate all patients when registering the five early acoustically evoked potentials.

THOUGH many new antibiotics have been found, the streptomycin series have not lost their importance. They are still one of the most effective remedies for all forms of tuberculosis. However, the use of streptomycin is limited by its additional neurotoxical and ototoxical affects. Such accompaniments were first described by Brown and Hinshaw.1 Since then, a great many clinical and experimental papers concerning the ototoxicity of basic streptomyces-antibiotics have been published.2-9Electrophysiological experiments of Stange et al9 concerning the efficiency of streptomycin-sulfate on excitation and adaptation of the hair-cells in the organ of Corti, especially, proved that streptomycin injures the metabolism of the sensory cells in the ear. It affects the cellular membrane and restricts its reabsorption.5 The result is an accumulation of streptomycin in the sensory cells and, consequently, loss of function.Experiments to reduce the ototoxic effect of streptomycin have been made for several years.

Zusammenfassung Das Auftreten toxischer Schäden am akustischen System — zentral wie peripher —, durch Streptomycinsulfat in 20facher therapeutischer Dosis verursacht, kann im Tierexperiment durch Lösung des Streptomycins in Ozothin weitgehend gemindert und bei vorheriger i. m. Injektion von Ozothin sogar verhütet werden. Bei dem wesentlich ototoxischeren Neomycinsulfat kann durch Ozothin eine weitgehende, signifikante Minderung der ototoxischen Wirkung erreicht werden. Die „in vivo-Versuche” an mit drei Infektionsarten infizierten Mäusen beweisen, daß das Ozothin im Vergleich zum Aqua bidest. die biologische Aktivität des Streptomycinsulfats weder abschwächt, noch verstärkt, also nicht beeinflußt. Somit zeigen these Untersuchungsergebnisse eindeutig, daß in der Klinik bei einer notwendigen Behandlung mit basischen Streptomyces-Antibiotica die Zugabe von Ozothin eine Verhütung ototoxischer Schäden ermöglichen und sogar eine Erhöhung der Streptomycindosen — unter strenger audiologischer Kontrolle — wahrscheinlich werden lassen kann.

Zusammenfassung: In den Jahren 1964 bis 1968 wurden in der Universittsklinik fr Hals-, Nasen- und Ohrenkrankheiten in Freiburg 78 Patienten mit pltzlicher Hrverminderung oder- verlusten ber 4–6 Wochen stationr behandelt. Der Behandlungsbeginn lag bei 41 Kranken innerhalb der ersten 6 Wochen (Gruppe a), bei 37 Patienten zwischen 6–24 Monaten nach Eintritt des akuten Krankheitsgeschehens (Gruppe b). Die Kranken erhielten tglich Complamin, Ozothin, Neurobion, Rovigon und jeden 2. Tag im Wechsel 7% ige NaHCO3-infusionen und Stellatumblockaden. Der Behandlungserfolg in beiden Gruppen ist signifikant unterschiedlich (3 σ). Die Gruppe a wies in den tiefen Frequenzen einen Behandlungserfolg von 15 dB, in den mittleren und hohen Frequenzen von durchschnittlich 20 dB, die Gruppe b 3–4 dB in den tiefen Frequenzen, 4–5 dB in den mittleren Frequenzen und 5–7 dB in den hohen Frequenzen auf nach 4–6 Wochen Behandlungsdauer. Bei einer weiteren Gruppe von Patienten, die zustzlich Gleichgewichtsstrungen hatten, war der Hrgewinn von den Frherfaten und Spterfaten ohne Gleichgewichtsstrungen unterschiedlich; im mittleren Frequenzbereich von 1–2 kHz zeigten auch diese Patienten den gleichen Hrgewinn von 20 dB am Ende der stationren Behandlung, konnten jedoch in tiefen Frequenzen von 0.06–0,5 kHz und in den hohen Frequenzen von 3,0–12,0 kHz durchschnittlich nur einen Hrgewinn von 8 dB am Ende der stationren Behandlung erreichen. — Bei 8 Patienten von 78 Erkrankungen konnte kein eindeutiger therapeutischer Erfolg erzielt werden, von denen 1 Patient der Gruppe a und 7 Patienten der Gruppe b angehrten. Das Behandlungsergebnis beweist die Notwendigkeit eines sofortigen Therapiebeginns nach Eintritt des akuten Hrsturzes. Eine lange Behandlungsdauer ist nicht nur berechtigt, sondern auch notwendig. Selbst bei Patienten, bei denen rasch ein normales Gehr innerhalb der ersten 2 Wochen nach Behandlungsbeginn erreicht werden konnte, ist noch eine weitere stationre Behandlung von etwa 10 Tagen notwendig, um Rezidive zu vermeiden. Im Durchschnitt setzt nach der 3. und in den hohen Frequenzen auch nach der 4. Wochen noch ein deutlicher, teils signifikanter Hrgewinn ein. So ist in den hohen Frequenzen bei den Patienten der Gruppe b erst in der 4. Woche berhaupt ein deutlicher Hrgewinn zu verzeichnen. Das Ergebnis hat weiterhin gezeigt, da die Patienten, bei denen gleichzeitig Gleichgewichtssymptome vorhanden sind, vor allem im mittleren Frequenzbereich von 1–2 kHz ein sehr guter Hrgewinn durch die Therapie ermglicht werden kann, whrend die hohen und tiefen Frequenzen einen mittleren Hrgewinn nur von 7 dB verzeichnen. Es hat sich also eindeutig ergeben, da bei Patienten ohne Strungen des Gleichgewichtsapparates der therapeutische Erfolg hinsichtlich des gesamten Frequenzbereiches wesentlich gnstiger ist. Bei Kontrollen bis 6 Monaten nach Therapiebeginn zeigt sich, da keine Rezidive zu verzeichnen sind, sondern noch Besserungen bis zu einem Hrgewinn von 30 dB vor allem bei der Gruppe a eintreten. — Ein vollstndiges Literaturverzeichnis bis zum Jahre 1965 befindet sich beiNeveling.

Zusammenfassung:

50%-DMSO-solution effects the following damage to the acoustic biopotentials (cochlear microphonics; excitation and adaptation of the compound action potentials of the acoustic nerve) of the cat:1.After application of DMSO into the external auditory meatus during 21 days:a)diminution of the threshold shift of 20 dB;b)severe damage to the outer hair cells of 65%;c)medium damage to the inner hair cells of 30%;d)disturbance of the metabolism of adaptation;e)severe damage to the hair cells of the basal turn of the cochlea.2.Acute 500/0-DMSO-damage:a)application into the external auditory meatus effects a damage to the compound action potentials of the acoustic nerve of 40% (during 6 hours);b)application into the middle-ear effects a damage to the compound action potentials of the acoustic nerve of 60% (during 6 hours).

After removal of the organ of Corti on one side, four sequential efferent compound action potentials were registered from the cochlear nerve of the same side upon click stimulation of the contralateral ear. For an input of 105 dB SPL, there were three early potentials having maximum average latencies of 2.3, 3.1, and 4.7 msec, and average amplitude of 60, 50, and 25 µV respectively.

In the present paper the input-output functions of the slow acoustically evoked potential are determined under the following conditions: vertex-, ipsi-lateral and contra-lateral pick-up. In all three modes of pick-up we got the input-output function of the high stimulus repetition rate;—this means: for the adapted stage of the system as well as that for the small repetition rate, the non-adapted stage. In all three modes of pick-up we found a different input-output-function and a difference between the adapted and the non-adapted stage. The simultaneous registration is more advisable than the successive one. We determined the normal characteristic curves of 10 adults in order to compare them with patients. The vertex-pick-up seems to be the best one for determining the threshold, whereas the contralateral pick-up seems to give more information about the pathological function of the acoustic system.

The method described in this paper enables the locomotor activity of small insects to be recorded. It is based on variations in capacitance within a bridge circuit, the variations being due to movements of the animals. The method is adapted to the use of multi-channel action recorders, thus allowing a greater number of sensor units to be employed simultaneously.

1. An Katzen, bei denen in Dial-Narkose das runde Fenster freigelegt worden war, wurde bei monauraler Beschallung in einer reflexionsfreien, elektrisch abgeschirmten Kammer mit Hilfe der Makroelektrodenrechnik am runden Fenster Reizfolgeströme und Summenaktionspotentiale abgeleitet.