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Direct effects of ONO-1101 ¿(-)-[(S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl-3-[4-[(S) -2-hydroxy-3-(2-morpholino carbonylamino)ethylamino] propoxy]phenylpropionate monohydrochloride), a novel beta-antagonist, on action potential parameters and membrane currents, and its beta adrenoceptor antagonism were examined in cardiac muscle. Action potential-parameters in papillary muscle of reserpinized animals and membrane currents recorded from single myocytes obtained from guinea pig and rabbit hearts were not affected by 1 to 100 microM ONO-1101. On the other hand, ONO-1101 markedly inhibited the potentiation of Ca current by isoproterenol in single cardiac myocytes of the guinea pig. The concentration-response relationship of Ca current for isoproterenol was shifted to the right. This effect resembled that of esmolol, which is also a beta adrenoceptor antagonist. A Schild plot analysis revealed the slope and pA2 value of each antagonist (ONO-1101, 0.94, 8.0; and esmolol, 0.98, 7.3, respectively) and demonstrated that ONO-1101 is about 5 times more potent than esmolol as a beta-antagonist. Two other effects of isoproterenol: 1) potentiation of delayed rectifier K current and 2) activation of chloride current, were also inhibited by ONO-1101. The time required for 50% removal of beta-antagonism of ONO-1101 and esmolol after the washout was estimated as 4 and 6 min, respectively, in depolarized papillary muscle. These results suggest that ONO-1101 is a potent beta-antagonist whose effects were removed quickly by washout. When applied at what is thought to be a clinical dosage, ONO-1101 had no direct effects on action potential-parameters and membrane currents in cardiac muscle. These characteristics of ONO-1101 suggest that this agent may be effective in clinical use.

A 12-year-old boy with growth hormone deficiency and partial diabetes insipidus resulting from transsphenoidal meningoencephalocele and with eye abnormalities is described. Fifteen other patients with transsphenoidal meningoencepalocele have been reported. Hypothalamic-pituitary dysfunctions were diagnosed by endocrinological studies in seven cases. It is important to recognize transsphenoidal meningoencephalocele as a cause of hypopituitarism, since some cases may have gone unrecognized. The association of hypothalamic-pituitary dysfunction and a midline craniocerebral anomaly has been reported in patients with cleft lip and/or palate, septo-optic dysplasia, the holoprosencephalies, and Kallmann syndrome. However, there was no evidence of transsphenoidal meningoencephalocele in these disorders and this may be a different form of midline craniocerebral and midfacial anomaly.

1. Ionic currents underlying the action potential were recorded from enzymatically isolated smooth muscle cells of guinea‐pig ureter. 2. The action potential recorded from a single cell was similar to that from a multicellular preparation. It showed repetitive spikes on a plateau potential which followed the first spike. Treatment with 10 mM‐tetraethylammonium (TEA) increased the amplitude and duration of the plateau phase and abolished the repetitive spikes. 3. Under voltage clamp mode, at least two (maybe three) kinds of outward currents were activated during depolarizing pulses. The main outward current was Ca2+‐dependent K+ current (IK(Ca], which was mostly blocked in Ca2+‐free solution, or by application of 1 mM‐cadmium (Cd2+) or 2 mM‐tetraethylammonium (TEA). IK(Ca) was greatly decreased by treatment with 5 mM‐caffeine or an addition of 10 mM‐EGTA in a pipette solution. 4. In the presence of 1 mM‐Cd2+ and 2 mM‐TEA, a small transient outward current remained. 4‐Aminopyridine (1 mM) suppressed the transient outward current by about 40%. Time‐ and voltage‐dependent delayed rectifier outward currents were small in ureter cells. An inwardly rectifying K+ current was not detected. 5. An application of 1 mM‐Cd2+, 5 mM‐cobalt (Co2+), 1 mM‐lanthanum (La3+) or 0.1 microM‐nifedipine completely blocked the action potential. Replacement of 80‐90% of extracellular Na+ with Li+ or Tris almost abolished the plateau potential and repetitive spikes but did not change significantly the first spike. 6. In the presence of 30 mM‐TEA, the inward current elicited by depolarization was monophasic and lasted for more than 1 s. Application of 1 mM‐Cd2+, 1 mM‐La3+, 0.1 microM‐nifedipine, or 5 mM‐Co2+ completely blocked inward current. The replacement (87%) of extracellular Na+ ions with Li+, Tris, sucrose or TEA speeded up the decay of inward current; the inward current decreased by 10‐60% at the end of a 500 ms pulse. 7. Even in low‐Na+ solution (120 mM‐TEA), the inactivation of ICa had a quite slow component (tau = 1 s), in addition to another faster component (tau = 100 ms) at 0 mV. When short depolarizing clamp pulses (50 ms) were repetitively applied at short intervals (50 ms) and with interpulse voltage of ‐10 or ‐20 mV to mimic the repetitive spikes on the plateau of the action potential, the decline of peak Ca2+ current during the train of pulses was smaller than the decay of Ca2+ current during a long pulse.(ABSTRACT TRUNCATED AT 400 WORDS)

We report a systematic investigation of the effect of n- and p-type doping on the AlGaAsGaAssuperlattice (SL) intermixing using photoluminescence. We find that the SL intermixing is not only enhanced by Si doping but also suppressed by Be doping. Although previous models have suggested the contribution of triply negatively charged Ga vacancies, V3 −Ga, in n-type and intrinsic materials and of doubly positively charged Ga interstitials, I2 +Ga, in p-type materials, we find that at 900°C the Al-Ga interdiffusion is mediated by singly negatively charged Ga vacancies, V−Ga, in both p- and n-type materials for n < 1 × 1018cm− 3. These results are shown to be explained consistently in terms of the Fermi-level effect. Our results demonstrate that the thermal stability of AlGaAsGaAsheterostructures can be controlled, i.e., weakened or strengthened, by appropriate tuning of the Fermi level.

An attempt was made to obtain electrophysiological evidence for continuous influx of Ca ion through voltage-dependent Ca channel (VDCC) in smooth muscle during long depolarization, for example in high K solution. Noninactivated Ca current [ICa(ni)] remaining after the accomplishment of voltage-dependent inactivation by prolonged depolarization for approximately 1 min was detected by three means under whole cell voltage clamp in several types of smooth muscle cells. The measurement of ICa(ni) was performed by micropuff application of Cd2+ or Ca2+ in the presence or absence of 5 mM extracellular Ca, respectively, or jump of extracellular Ca concentration [( Ca]o). The current-voltage relationship of ICa(ni) evaluated by these means had a peak at approximately -10 mV. The peak amplitude ranged from 5 to 25 pA, depending on whether the cells were isolated from guinea pig urinary bladder, ureter, vas deferens, taenia caecum, or rabbit portal vein. The ICa(ni) may be large enough to explain sustained contraction in high K solution, at least in these smooth muscle tissues. A window current simulated from the steady-state activation and inactivation curves and the maximum conductance of Ca current (ICa) in these cells suggests a theoretical basis for the observed ICa(ni).