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7-Hydroxyguanine, an antitumor purine-analog, reacted with ribose (or deoxyribose)-1-phosphate in the presence of purine nucleoside phosphorylase. We prepared 7-hydroxyguanine riboside and deoxyriboside using purine nucleoside phosphorylase from bovine spleen. Each nucleoside exhibits antitumor activity against mouse leukemia L1210 cells. The therapeutic effect of 7-hydroxyguanine deoxyriboside is superior to those of 7-hydroxyguanine and 7-hydroxyguanine riboside.

This report describes a female patient with childhood form of acid maltase deficiency who survived till fifteen years old. Although acid alpha-1,4-glucosidase was deficient in the liver, kidney, skeletal and cardiac muscles, neutral alpha-1,4-glucosidase was present in normal concentrations in those organs. On light microscopic examination, numerous intracytoplasmic vacuoles containing acid phosphatase positive granules and PAS positive materials were present in both type 1 and 2 A fibers, predominantly in the latter. The striking finding in the present case was a selective type 2 fiber atrophy with type 2 B fiber deficiency believed to result from type 2 motor neuron dysfunction in the spinal cord. Electron microscopic study revealed extensive glycogen particle accumulation, autophagic vacuoles and myelin figures in the muscle fibers.

B-16 melanoma cells in culture were prelabeled with (3H)-arachidonate, and exposed to UV radiation. Immediately after irradiation the cells released labeled materials. This UV-stimulated release was inhibited by mepacrine (20 microM) and calmodulin inhibitor W7 (0.5 microM). To determine the influence of extracellular Ca2+ on the UV-stimulated release, experiments were made with media containing various concentrations of Ca2+. The release decreased significantly at lower Ca2+ concentrations. These results suggest that Ca2+-calmodulin-dependent phospholipase A2 was involved in UV-stimulated release of radiolabeled materials, possibly arachidonic acid and its metabolites, from the cells.

Sequences (ndhA-F) homologous to human mitochondrial genes for components of the respiratory chain NADH dehydrogenase have been found in the chloroplast DNA of tobacco. The ndhA, D, E and F sequences corresponding to the mitochondrial URF1, 4, 4L and 5 are located in the small single copy region, the ndhB sequence corresponding to URF2 in the inverted repeat and the ndhC sequence corresponding to URF3 in the large single copy region of the chloroplast DNA. Northern blot hybridization revealed that all six ndh sequences are actively expressed in the chloroplasts. The ndhA and ndhB sequences contain single introns and the splice sites of their pre-mRNAs were determined by reverse transcription analysis. These findings suggest that potential components of an NADH dehydrogenase are synthesized in the chloroplasts.

The effect of alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), a new anti-inflammatory compound, on arachidonate lipoxygenase and cyclooxygenase was investigated. KME-4 showed a dose-dependent inhibition of 5-lipoxygenase activity in both the cytosol (IC50: 0.85 microM) and ionophore A23187-stimulated cells (IC50: 11.5 microM) of guinea pig peritoneal polymorphonuclear leukocytes. KME-4 was also found to inhibit rabbit platelet cyclooxygenase (IC50: 0.44 microM), but had no inhibitory effect on platelet 12-lipoxygenase at concentrations up to 100 microM, whereas BW755C inhibited both enzymes in the same range of concentrations. The results indicate that KME-4 is a dual 5-lipoxygenase and cyclooxygenase inhibitor which is different from BW755C in affecting 12-lipoxygenase. These effects may provide information for understanding the pharmacological activity of KME-4.

The effects of vitamin E, vitamin B2 and selenite on DNA single strand breaks induced by Na2CrO4 were examined by alkaline elution. Incubation of Chinese hamster V-79 cells with alpha-tocopherol succinate (vitamin E) for 24 h prior to exposure to Na2CrO4 resulted in a decrease of DNA breaks produced by this compound. However, similar pretreatment with riboflavin (vitamin B2) or Na2SeO3 resulted in an enhanced formation of breaks induced by Na2CrO4. Pretreatment with Na2SeO3 resulted in increased levels of glutathione in these cells while levels of glutathione remained the same with vitamin E or vitamin B2. These results suggest that Na2CrO4 induced DNA breaks appear to be mediated by the formation of free radicals and/or cellular reductive metabolism.

DNA polymerase activity was determined in hyperkeratotic epidermis of the guinea pig by topical application of n.hexadecane. Epidermal cells were separated by Percoll gradient centrifugation. DNA polymerase alpha activity was higher in the basal cells, but polymerase beta activity was higher in granular cells than in cells from the other layers. The hyperkeratosis was accompanied by an increase in polymerase alpha activity in both the squamous and basal cells. However, polymerase beta activity decreased in the granular cells and was distributed almost uniformly across the epidermis. The distribution pattern of polymerase activities in the hyperkeratotic epidermis was not simply an enhancement of the pattern in normal epidermis.

KME-4,alpha-(3,5-di-t-butyl-4-hydroxybenzylidene)-gamma-buty rolactone was found to reduce the accumulation of leucocytes and exudate volume in the rat carrageenan pleurisy model. When administered orally 1 h before carrageenan, KME-4 (3-10 mg kg-1) induced a degree of inhibition of leucocyte migration almost equal to that of indomethacin (3-10 mg kg-1) in both 5 h and 24 h pleurisies. Furthermore, KME-4, when administered orally 5 h after the carrageenan, inhibited both monocyte numbers and exudate volume in a 24 h pleurisy and was more effective than indomethacin and BW755c which inhibited only monocyte migration. These results suggest that KME-4 has a differential anti-inflammatory activity. Dexamethasone (0.25 mg kg-1) showed strong inhibition of total cell numbers and exudate volume.

In this general pharmacological study of N-[2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), its effects on the cardiovascular and respiratory systems were studied. SUN 1165, at doses of up to 1.0 mg/kg i.v., had almost no effect. SUN 1165, at doses of 3.0 and 6.0 mg/kg i.v., caused dose-dependent decreases in blood pressure, common carotid, vertebral, coronary, hepatic and femoral artery and portal vein blood flows, cardiac contractility, heart rate and myocardial oxygen consumption. SUN 1165 increased urine volume and urinary excretion of electrolytes in rats at a dose of 100 mg/kg p.o. SUN 1165 decreased renal plasma flow and urinary excretion of electrolytes in anesthetized dogs at 6.0 mg/kg i.v., but at the antiarrhythmic doses (1.0-3.0 mg/kg i.v. in dogs), it had almost no effects on renal function. SUN 1165 had almost no effect on the autonomic nervous systems in anesthetized dogs. These results suggest that SUN 1165 at the antiarrhythmic doses do not have any effects on the respiratory and cardiovascular systems, renal function and autonomic nervous systems in rats and dogs, but that when administered at high doses, it has inhibitory effects on respiratory and cardiovascular system and renal function. In conclusion, SUN 1165 seems to be a novel antiarrhythmic drug relatively free of cardiovascular, respiratory, renal and autonomic effects.

The individual muscle fibers of the anterior byssus retractor muscle (ABRM) of Mytilus edulis L. are uninucleate, 1.2-1.8 mm in length, 5 microm in diameter, and organized into bundles 100-200 microm in diameter, surrounded by connective tissue. Some bundles run the length of the whole muscle. Adjacent muscle cell membranes are interconnected by nexuses at frequent intervals. Specialized attachments exist between muscle fibers and connective tissue. Electrical constants of the resting muscle membrane were measured with intracellular recording electrodes and both extracellular and intracellular current-passing electrodes. With an intracellular current-passing electrode, the time constant tau, was 4.3 +/- 1.5 ms. With current delivered via an extracellular electrode tau was 68.3 +/- 15 ms. The space constant, lambda, was 1.8 mm +/- 0.4. The membrane input resistance, R(eff), ranged from 23 to 51 MOmega. The observations that values of tau depend on the method of passing current, and that the value of lambda is large relative to fiber length and diameter are considered evidence that the individual muscle fibers are electrically interconnected within bundles in a three-dimensional network. Estimations are made of the membrane resistance, R(m), to compare the values to fast and slow striated muscle fibers and mammalian smooth muscles. The implications of this study in reinterpreting previous mechanical and electrical studies are discussed.

1. In the nerve-muscle preparation, where catch was characteristically minimal, 5-hydroxytryptamine (5-HT) had no effect on resting membrane potential, junction potentials, spikes or contraction.2. In muscle bundles, where catch was prominent, 5-HT did not change membrane potentials, but prolonged junction potentials and lowered the threshold for spike discharge and contraction.3. In muscle bundles, exposed to high concentrations of 5-HT, depolarization evoked repetitive spikes, while in low 5-HT, spikes were seldom fired even with much greater depolarization.4. In muscle bundles, the effective membrane resistance, R(eff.), decreased from 45-60 to 23-35 MOmega as 5-HT concentration was increased.5. It is suggested that 5-HT may facilitate spike discharge by lowering the internal free Ca(2+) concentration.

Field stimulation of the jejunum elicited successively an action potential of spike form, a slow excitatory depolarization, a slow inhibitory hyperpolarization, and a postinhibitory depolarization as a rebound excitation. The slow depolarization often triggered the spike. The inhibitory potential showed lower threshold than did the excitatory potential. Both the excitatory potentials were abolished by atropine and tetrodotoxin. Effective membrane resistance measured by the intracellular polarizing method was reduced during the peak of the excitatory potential, but the degree of reduction was smaller than that evoked by iontophoretic application of acetylcholine. Conditioning hyperpolarization of the muscle membrane modified the amplitude of the excitatory potential. The estimated reversal potential level for the excitatory potenialt was about 0 mv. No changes could be observed in the amplitude of the inhibitory potential when hyperpolarization was induced with intracellularly applied current. Low [K](o) and [Ca](o) blocked the generation of the excitatory potential but the amplitude of the inhibitory potential was enhanced in low [K](o). Low [Ca](o) and high [Mg](o) had no effect on the inhibitory potential.

1. The electrical properties of red muscle fibres of the silver carp (Carassius auratus (Linné)) were investigated and compared with those of white fibres. The resting membrane potential of red muscle was -73.1 mV, and of white muscle -82.4 mV. The effective resistance of fibre, time constant and space constant were 1.43 MOmega, 26.6 msec and 2.1 mm for red muscle and 1.0 MOmega, 48.4 msec and 1.9 mm for white muscle.2. The membrane capacitance in red muscle was 2.55 muF/cm(2) and in white muscle was 7.23 muF/cm(2), though the sarcoplasmic reticulum and the transverse tubular system were developed equally in both tissues.3. No rectification could be observed in the current-voltage relation in both the muscles. However, in excess potassium solutions, both types of muscle showed anomalous rectification.4. In red muscle it was rare to trigger a spike by nerve stimulation or by field stimulation of the tissue. However, in white muscle, there appeared graded responses and occasionally spikes were generated with overshoot potentials.5. Excess potassium concentration produced contracture in the red muscle, but even forty times of normal potassium never produced contracture in the white muscle.

1. The effects of adrenaline and noradrenaline on neuromuscular transmission and the question of whether these catecholamines act on the presynaptic nerve terminal or on the post-synaptic membrane were investigated using the fin muscles of the silver carp.2. Noradrenaline (10(-8)-10(-6) g/ml.) had no effect on membrane potential or input resistance of the membrane. In contrast, adrenaline (10(-8)-10(-6) g/ml.) hyperpolarized the membrane and increased the input resistance.3. Noradrenaline had no effect on the amplitude of the miniature junction potentials but caused them to become more frequent.4. Adrenaline enhanced the amplitude of the miniature junction potentials and slightly increased their frequency. These effects of adrenaline were partly due to the increased input resistance of the post-synaptic membrane, and probably did not involve the presynaptic terminals.5. Both noradrenaline and adrenaline increased the amplitude and prolonged the falling phase of the excitatory junction potentials (e.j.p.s).6. Noradrenaline enhanced the amplitude and prolonged the duration of the extracellularly recorded excitatory junction current. No such effect was observed with adrenaline.7. Adrenaline but not noradrenaline enhanced the amplitudes of acetylcholine potentials evoked by iontophoretic application of acetylcholine.8. Noradrenaline and adrenaline had no effect on the compound action potentials of the nerve supplying the red muscle, recorded by the sucrose gap method.