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Biomedical subjects

M Kuno

Publications and source records attributed to M Kuno.

At least 109 records · Page 6Linked to original sources

Quantal analysis of a decremental response at hair cell-afferent fibre synapses in the goldfish sacculus.

1. On application of a step decrement in the sound intensity, the amplitude of excitatory post-synaptic potentials (e.p.s.p.s) recorded intracellularly from large afferent auditory fibres in goldfish's sacculus showed a decremental response in which the amplitude of the e.p.s.p.s was temporarily reduced to a very low level, but soon returned to a new steady level appropriate to the decreased sound intensity. This response seems to underlie the temporary reduction in the rate of afferent discharge observed in the mammalian cochlea upon cessation of sound or upon reduction of its intensity 2. A statistical analysis revealed that reduction in the size of the mean quantal content (m) during the decremental response was associated with reduction in the size of binomial population (n), but not that of the probability (p) of any one of the available quanta actually being used. 3. The temporary reduction in the size of n during the decremental responses can be explained if it is assumed that replenishment to vacant release sites was channelled to high threshold sites and that the low threshold sites were bypassed. The mechanism underlying this special type of replenishment is discussed in relation to the ultrastructural features of presynaptic sites in the hair cell.

Animals↗

Beta-lactamase inhibitory activities and synergistic effects of 5,6-cis-carbapenem antibiotics.

Twelve 5,6-cis-carbapenem antibiotics were examined for their beta-lactamase inhibitory activities, their types of inhibitions, and their synergistic activities with other beta-lactam antibiotics. All the carbapenems inhibited eight types of beta-lactamases including cephalosporinases which were insensitive to clavulanic acid and sulbactam. The sulfonyloxy ethyl carbapenems were the most active inhibitors; they inhibited all beta-lactamases in a progressive fashion, whereas some of the hydroxyl compounds exerted non-progressive inhibition against several beta-lactamases such as those of Escherichia coli TN713 and Proteus vulgaris GN4413. Several carbapenems were inactivated by the beta-lactamases of Citrobacter freundii GN1706, P. vulgaris GN4413, E. coli TN713, and Klebsiella pneumoniae TN1698. Most of the carbapenems potentiated the antibacterial activities of ampicillin and cefotiam against beta-lactamase-producing bacteria.

Anti-Bacterial Agents↗

Do identical activity patterns in fast and slow motor axons exert the same influence on the twitch time of cat skeletal muscle?

1. The fast-twitch flexor digitorum (the lateral head; equivalent to the flexor hallucis longus) and slow-twitch soleus muscles of the cat were denervated, and the two nerves immediately reunited to one or the other muscle. Contraction times of the dually reinnervated muscle were examined 9 weeks post-operatively in response to separate stimulation of its own and the foreign nerve. Over a 5 week period before the terminal experiment, a variety of artificial activity patterns was imposed on the two nerves.2. Following the dual-union operation, the flexor digitorum muscle was preferentially reinnervated by its own nerve. In contrast, the soleus muscle showed no evidence of preferential reinnervation.3. When neural activity was not artificially modified, the dually reinnervated flexor digitorum or soleus muscle showed faster contractions in response to stimulation of the flexor digitorum nerve than to stimulation of the soleus nerve.4. Following a 5 week period in which neural activity was virtually eliminated by cord transection or in which the two nerves were stimulated at the same frequency, the contraction times of the dually reinnervated soleus muscle were the same in response to stimulation of either nerve.5. In contrast, under the experimental conditions described above (cord transection or nerve stimulation), the dually reinnervated flexor digitorum muscle showed a significantly faster contraction in response to stimulation of its own nerve than to stimulation of the soleus nerve.6. It is concluded that, when neural activity is absent or identical in pattern, motoneurones normally innervating the fast- or slow-twitch muscles exert the same influence on contraction times of the soleus muscle.7. The dependence of contraction times of the dually reinnervated flexor digitorum muscle upon the type of the innervating motoneurone may be explained either by selective reinnervation of a particular group of muscle fibres or by different trophic substances emanating from the motoneurones.

Action Potentials↗

Beta-lactamase stability and antibacterial activity of cefmenoxime (SCE-1365), a novel cephalosporin.

Cefmenoxime, a new cephalosporin antibiotic, has been shown to be stable to a Staphylococcus aureus penicillinase and R plasmid-mediated type I and type IV penicillinases. It was also resistant to hydrolysis by most cephalosporinases, but was susceptible to hydrolysis by a Proteus vulgaris beta-lactamase. Cefmenoxime was active against cephaloridine-resistant species, except Pseudomonas aeruginosa, which was moderately resistant to cefmenoxime. Cefmenoxime was an inducer of P. vulgaris beta-lactamase biosynthesis, but 1 microgram or more of the drug per ml, which inhibits most of the clinical isolates of P. vulgaris, was required for the production of detectable amounts of the enzyme. Cefmenoxime was a strong competitive inhibitor of beta-lactamases of Enterobacter cloacae, Citrobacter freundii, P. aeruginosa, and Serratia marcescens, but it did not inhibit penicillinases in spite of its resistance to hydrolysis.

Anti-Bacterial Agents↗

C-19393 S2 and H2, new carbapenem antibiotics. IV. Inhibitory activity against beta-lactamases.

New carbapenem antibiotics, C-19393 S2 and H2, have been found to be potent and broad-spectrum inhibitors of beta-lactamases. Among 11 types of beta-lactamases tested, those from Escherichia coli (plasmid-bearing), Klebsiella pneumoniae, Proteus vulgaris, Serratia marcescens and Bacteroides fragilis were especially sensitive. They also inhibited cephalosporinases insensitive to clavulanic acid. The inhibition by C-19393 S2 and H2 was of progressive type, except for the inhibition of E. coli enzyme (plasmid-mediated type I) by C-19393 H2. The inhibition of E. coli beta-lactamase by C-19393 S2 was irreversible, while that by C-19393 H2 was reversible.

Anti-Bacterial Agents↗

Enhancement of synaptic function in cat motoneurones during peripheral sensory regeneration.

1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from medial (m.g.) and lateral gastrocnemius (l.g.) motoneurones in the cat 2-30 weeks after crushing the m.g. nerve.2. The mean amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were initially depressed (2-3 weeks after injury) and subsequently reached levels greater than normal for a period (8-12 weeks) before slowly declining to about 70% of the normal values (by week 30).3. Monosynaptic e.p.s.p.s evoked in m.g. motoneurones from the intact l.g. nerve showed neither initial depression nor subsequent alterations following crush of the m.g. nerve.4. By the eighth week after nerve crush, about 70% of Group I and Group II sensory fibres in the m.g. nerve responded to muscle stretch, about 15% had regenerated into the muscle but did not respond to muscle stretch, and the remainder failed to regenerate across the neuroma formed by the nerve crush.5. Homonymous, monosynaptic e.p.s.p.s produced by impulses in single sensory fibres responding to stretch of the m.g. muscle were recorded 8 weeks after crush of the m.g. nerve. Their amplitude distribution was indistinguishable from that obtained in normal, unoperated cats. Thus, there was no evidence that functionally reinnervated sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s observed during peripheral regeneration.6. When the m.g. nerve had been sectioned and prevented from regenerating into the muscle for 8 weeks, the amplitudes of homonymous and heteronymous e.p.s.p.s evoked from the m.g. nerve were significantly smaller than those observed in control animals. Thus, there was no evidence that non-regenerating sensory fibres are responsible for the enhanced phase of composite e.p.s.p.s after nerve crush.7. It is suggested that the sensory fibres responsible for abnormally large composite e.p.s.p.s following nerve crush are those that regenerate into the muscle but do not achieve functional reinnervation. This possibility is discussed in relation to the increase in central synaptic efficacy observed after prolonged disuse of the sensory pathway.

Animals↗

Reaction of synapses on motoneurones to section and restoration of peripheral sensory connexions in the cat.

1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s.) were recorded from triceps surae motoneurones of the cat 2-8 months after section of the medial gastrocnemius nerve whose regeneration into the muscle was prevented. In other animals, the cut nerve was reunited to the muscle with a post-denervation delay varying from 2 to 6 months, and the e.p.s.p.s were recorded 2 months later. The e.p.s.p.s were evoked by stimulation of the medial gastrocnemius nerve central to the site of the section or reunion. 2. The mean amplitudes of the e.p.s.p.s decreased with time after nerve section, virtually disappearing by the eighth post-operative month. The decrement of the e.p.s.p. amplitude occurred more quickly in soleus motoneurones than in medial or lateral gastrocnemius motoneurones. 3. The e.p.s.p.s evoked in medial or lateral gastrocnemius motoneurones from the cut medial gastrocnemius nerve returned to normal levels 2 months after reunion of the cut nerve even following a post-denervation delay of 6 months. However, in soleus motoneurones the e.p.s.p. recovery was incomplete. 4. The degree of functional motor reinnervation of the medial gastrocnemius muscle depended upon the post-denervation delay preceding the reunion operation. With a delay of 6 months before the reunion, the muscle showed no or only weak contractions in response to nerve stimulation. 5. Axotomized medial gastrocnemius motoneurones showed a significant decrease in conduction velocity and significant increase in the amplitude of overshoot of action potentials. The changes persisted even when the cut nerve was reunited to the muscle 2-6 months after denervation. 6. When the cut medial gastrocnemius nerve was reunited to the muscle 4 months after denervation, most of the sensory fibres, tested 2 months later, failed to respond to muscle stretch. 7. It is concluded that recovery of monosynaptic e.p.s.p.s following reconnexion of the cut nerve with its muscle does not require recovery of muscle activity, full restoration of sensory activity or the recovery of normal motoneurone properties. 8. It is also suggested that the degree to which central synaptic efficacy declines and recovers following section and regeneration of a peripheral nerve depends partly upon the type of motoneurone (fast phasic or slow tonic) with which the sensory fibres form synaptic connexions.

Animals↗

Dependence of motoneurone properties on the length of immobilized muscle.

1. The soleus muscle of adult cats was fixed in a shortened or lengthened position for 2 weeks by immobilizing the leg with a plaster cast. To eliminate the effects of reflex activity arising from the muscle, the lumbosacral dorsal roots were sectioned on the side of leg immobilization.2. The soleus muscle showed a significant decrease in weight after immobilization in a shortened position. Immobilization of the muscle in a lengthened position produced no significant changes in its weight.3. Two weeks after transection of the throacic spinal cord, the soleus muscle showed a significant decrease in weight. This decrease was prevented by immobilization of the muscle in a lengthened position. Immobilization in a shortened position caused no further muscle atrophy in cord-transected animals.4. Soleus motoneurones showed a significant decrease in the duration of after-hyperpolarization (a.h.p.) 2 weeks after immobilization of the muscle in a shortened position, whereas immobilization of the muscle in a lengthened position caused no significant changes in the duration of a.h.p.5. A decrease in the duration of a.h.p. of soleus motoneurones induced by cord transection was significantly prevented by immobilization of the muscle in a lengthened position but not by immobilization in a shortened position.6. In a variety of experimental conditions, the mean duration of a.h.p. of soleus motoneurones was significantly correlated with the soleus muscle: body wt. ratio.7. It is concluded that certain motoneurone properties depend upon the condition of the innervated muscle and that the primary factor responsible for the trophic influence is metabolic change in the muscle rather than contractile activity itself.

Animals↗

Disuse enhances synaptic efficacy in spinal mononeurones.

1. Monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) were recorded from triceps surae motoneurones in the cat following section or chronic conduction block of the medial gastrocnemius (m.g.) nerve with tetrodotoxin (TTX) or after daily stimulation of the sciatic nerve. 2. The mean maximum amplitudes of homonymous and heteronymous monosynaptic e.p.s.p.s evoked by stimulation of the mg. nerve were reduced significantly between 1 and 2 weeks after section of the muscle nerve. The mean amplitudes of monosynaptic e.p.s.p.s produced in the same motoneurones by afferent volleys from the intact synergists showed no significant alterations. 3. Reduction of the amplitude of monosynaptic e.p.s.p.s. evoked by the sectioned m.g. afferent volleys was not prevented by daily stimulation of the sciatic nerve. The chronic stimulation of the sciatic nerve did not increase the amplitude of monosynaptic e.p.s.p.s evoked by stimulation of the intact, lateral gastrocnemius (l.g.) or soleus nerve. 4. Chronic conduction block of the intact m.g. nerve with TTX cuffs for 2 weeks resulted in a significant increase in the homonymous e.p.s.p. amplitude. The amplitude of the heteronymous e.p.s.p.s evoked in the same m.g. motoneurones by stimulation of the intact l.g. or soleus nerve showed no significant changes. 5. It is concluded that decreased central synaptic transmission following section of the peripheral nerve is not due to elimination of impulse activity (disuse) of the sensory input and that prolonged disuse of the sensory fibres causes an increase, rather than a decrease, in central synaptic efficacy.

Animals↗

Evidence for the maintenance of motoneurone properties by muscle activity.

1. Electrophysiological properties of soleus motoneurones in adult cats were examined with intracellular electrodes following alterations of activity of the soleus muscle induced by transection of the thoracic spinal cord or by conduction block of the muscle nerve with tetrodotoxin (TTX) cuffs. Attempts were also made to maintain muscle activity by daily stimulation of the maintain muscle activity by daily stimulation of the peripheral nerve. 2. Within 8 days after transection of the thoracic cord, soleus motoneurones showed a significant decrease in the duration of afterhyperpolarization following action potentials. This change in motoneurone properties induced by cord transection was prevented by daily stimulation of the sciatic nerve. 3. Soleus motoneurones showed a significant decrease in the duration of after-hyperpolarization within 8 days after conduction block of the soleus nerve with TTX. This change in montoneurone properties was prevented by daily stimulation of the nerve peripheral to the TTX cuff but not central to the cuff. 4. The soleus muscle showed a significant decrease in weight relative to body weight within 8 days after transection of the thoracic cord. This decrease in muscle weight following cord transection was prevented by daily stimulation of the sciatic nerve. 5. No fibrillation was detected in the soleus muscle 8 days after conduction block of the soleus nerve with TTX. The maximum twitch tension of the soleus muscle evoked by nerve stimulation showed no significant difference between the two sides treated and untreated with TTX. Fast axoplasmic transport measured with cholinesterase as a marker was not affected by TTX. Thus, there was no sign of functional although morphological abnormalities were found in some nerve fibres. 6. It is concluded that motoneurone properties in an adult depend partly upon some factors associated with activity of the innervated muscles and that such trophic signals are retrogradely carried by the motor axons.

Action Potentials↗

Disparity of motoneurone and muscle differentiation following spinal transection in the kitten.

1. The spinal cord of kittens, 3--5 days of age, was transected at the lower thoracic level. Isometric contractions of the medial gastrocnemius and soleus muscles as well as intracellular potentials of their motoneurones were recorded after varying post-operative periods of up to 110 days. Similar observations were made 52--59 days after cord transection in adult cats. 2. In cord-transected kittens, contraction time of the gastrocnemius muscle showed normal development, whereas the soleus muscle failed to maintain slow contraction. In adult cats, cord transection increased the speed of contraction in the soleus muscle without significant changes in contraction times of the gastrocnemius muscle. 3. Soleus motoneurones showed a normal post-natal increase in the duration of afterhyperpolarization (a.h.p.) up to a certain stage (61--71 days in age) following cord transection. However, the subsequent increase in the duration of a.h.p. of soleus motoneurones observed in normal kittens was lacking in cord-transected kittens. It is suggested that soleus motoneurones show two stages of differentiation in terms of the duration of a.h.p. 4. In adult cats, cord transection caused a decrease in the duration of a.h.p. of soleus motoneurones approximately to the value observed at the end of the first stage of differentiation in kittens. 5. The duration of a.h.p. of gastrocnemius motoneurones remained virtually unchanged follwoing cord transection in both kittens and adult cats. 6. The positive correlation between the duration of a.h.p. of soleus motoneurones and contraction time of the innervated muscle fibres normally observed in kittens and adult cats was absent following cord transection. 7. It was assumed that alteration s in contraction time of the muscle following cord transection are due to virtual elimination of motoneurone discharge and that the duration of a.h.p. reflects the discharge pattern of motoneurones under normal conditions. Based on these assumptions, a possible process for normal post-natal differentiation of motoneurone and muscle is proposed.

Age Factors↗

Reaction of intact spinal motoneurones to partial denervation of the muscle.

1. The properties of soleus motoneurones of the cat were examined with intracellular electrodes about 3 weeks after partial denervation of the soleus muscle. Soleus motoneurones whose axons had been left intact were distinguished from those whose axons had been sectioned by the presence or absence of muscle contraction in response to intracellular stimulation of each motoneurone. 2. The average twitch tension of motor units evoked by intracellular stimulation of intact soleus motoneurones after partial denervation of the muscle was not significantly different from that observed in control, unoperated cats. Therefore, it was assumed that the majority of intact motoneurones had not been subject to injuries in their axons upon partial denervation. 3. Soleus motoneurones whose axons had been sectioned showed a significant increase in overshoot of action potentials and a significant decrease in resting membrane potential, in axonal conduction velocity and in the duration of after-hyperpolarization. 4. Soleus motoneurones whose axons had been left intact also showed a significantly shorter after-hyperpolarization than that seen in control, unoperated cats. Other electrophysiological properties of the intact soleus motoneurones were indistinguishable from those observed in unoperated animals. 5. The decrease of the duration of after-hyperpolarization in intact soleus motoneurones was greater in highly denervated preparations than in moderately denervated preparations. 6. The decrease of the duration of after-hyperpolarization in intact soleus motoneurones was associated with a decrease in contraction times of the innervated muscle fibres, the former preceding the latter by one to two weeks. 7. It is concluded that motoneurone properties can be modified without injury to their axons and that alterations in the properties of intact motoneurones depend upon the degree of partial denervation of the muscle. The possible signal for alterations of motoneurone properties is discussed. 8. It is also concluded that the contractile properties of muscle fibres can be modified without cross-union of the nerves. It is suggested that the contractile properties of muscle fibres may be linked to the duration of after-hyperpolarization or to some mechanism related to this factor in the innervating motoneurones.

Action Potentials↗

Membrane properties and conduction velocity in sensory neurones following central or peripheral axotomy.

1. The properties of dorsal root ganglion cells in the lumbosacral segments were examined with intracellular electrodes about 3 weeks after section of the central (dorsal roots) or peripheral processes in the cat.2. Chronic section of the peripheral nerve in the hind limb resulted in a reduction in conduction velocity of both the central and peripheral processes of sensory neurones.3. Sensory neurones arising from the triceps surae and plantaris muscles were subject to ;disuse' conditions for about 3 weeks by section of the ventral roots combined with severance of the Achilles tendon. Under such conditions, the central and peripheral conduction velocities of these sensory neurones tended to decrease, but the decrease was significantly less than that following peripheral nerve section.4. Chronic section of the dorsal roots produced no significant changes in conduction velocity of the central processes of muscle sensory neurones but caused a significant increase in the peripheral conduction velocity.5. The only electrophysiological property of dorsal root ganglion cells which altered following axotomy was the time-dependent membrane rectification in response to hyperpolarizing current pulses. The rectification characteristics were modified by chronic section of the peripheral nerve but not by chronic section of the dorsal root.6. It is concluded that injuries in nerve fibres per se do not necessarily result in a decrease of their conduction velocity and that a decrease in their conduction velocity is associated with changes in the properties of the cell bodies.7. It is suggested that a decrease in conduction velocity following nerve section may require the participation of changes in the neurone cell body.

Animals↗