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M Kuno

Publications and source records attributed to M Kuno.

At least 91 records · Page 5Linked to original sources
PubMed1986

Effects of nerve growth factor on the survival and synaptic function of Ia sensory neurons axotomized in neonatal rats.

Sensory neurons with small diameters (A delta and C cells) are known to be responsive to exogenous NGF even at postnatal stages. We have examined whether large Group Ia sensory neurons (A alpha cells) arising from muscle spindles are also responsive to NGF in neonatal rats. For this purpose, monosynaptic excitatory postsynaptic potentials (EPSPs) were evoked in spinal motoneurons by Group Ia muscle afferent volleys. When a muscle nerve was crushed on the day after birth, the monosynaptic EPSPs elicited by afferent volleys from the muscle were depressed within several weeks. This synaptic depression was partially reversed by daily treatment with NGF. NGF treatment also enhanced the EPSPs evoked by stimulation of intact muscle nerves, but this effect was less marked than that on the EPSPs produced by stimulation of the previously crushed muscle nerve. Exogenous NGF was effective for the EPSPs when the treatment began on the day after birth but not when the treatment began 4 d after birth. Following crush of a muscle nerve on the day after birth, about 45% of the sensory neurons derived from the muscle were lost. The cell death of small sensory neurons was prevented by daily treatment with NGF, whereas the NGF treatment was ineffective in preventing the cell death of large sensory neurons. The results indicate that Group Ia sensory neurons are responsive to NGF during early postnatal life.

Animals↗
PubMed1985

Central chemosensitivity to H+ and CO2 in the rat respiratory center in vitro.

The brainstem, cervical cord and attached phrenic nerve were excised from newborn rats and superfused in vitro. Respiratory output was measured by integration of phrenic nerve discharges. Respiratory output was enhanced by an increase in pCO2 at constant pH as well as by decreased pH with constant pCO2. It is concluded that the adequate stimulus to central chemoreceptors is not restricted only to H+.

Animals↗
PubMed1985

Nerve growth factor enhances central synaptic function of Ia sensory neurons.

Daily treatment of neonatal rats with nerve growth factor (NGF) significantly enhanced monosynaptic excitatory postsynaptic potentials (EPSPs) evoked in spinal motoneurons by muscle afferent volleys. A few weeks after crush of a muscle nerve, the EPSPs elicited by afferent volleys from the muscle nerve were markedly depressed. This synaptic depression could be partly prevented by daily application of NGF. It is concluded that central synaptic function of Ia sensory neurons is responsive to exogenous NGF in postnatal animals.

Animals↗
PubMed1985

Effect of beta-lactamase induction on susceptibility to cephalosporins in Enterobacter cloacae and Serratia marcescens.

For Enterobacter cloacae GN5797 and Serratia marcescens 72-2, which produce inducible beta-lactamases and respond antagonistically to many combinations of cephalosporins, the changes in beta-lactamase activity and sensitivity to cephalosporins were examined during semi-continuous cultivation in which the concentration of inducers was decreased by two-fold dilution of the culture every 30 min starting from 1 h after the addition of inducers. The levels of beta-lactamase, which peaked at 0.5-2 h after induction, decreased concomitantly with the disappearance of the inducers in the culture, and returned to the uninduced levels by 6 h. The ability of cefoxitin and cefmetazole to induce beta-lactamases was more potent than that of cefazolin and cefotiam. The sensitivity to some cephalosporins, judged by the MIC and bactericidal effect, was slightly decreased at an early stage of induction, and reverted to the uninduced levels within several hours after the inducers were depleted.

Cephalosporins↗
PubMed1985

Differential effects of carbon dioxide and pH on central chemoreceptors in the rat in vitro.

The brain stem, cervical cord and attached phrenic nerve were excised from neonatal rats and superfused in vitro. Respiratory activity was recorded from the phrenic nerve following transection of all the cranial nerves and dorsal roots. The frequency of spontaneous periodic activity recorded from the phrenic nerve was 6-14/min during superfusion with a saline solution equilibrated with 5% CO2 in O2 at 25 degrees C (pH 7.3). The magnitude of respiration was estimated from the peak value of phrenic activity integrated for each 0.1 s period. When the pH of the superfusion fluid was altered by changing the HCO3-concentration at constant PCO2, respiratory activity increased in low pH and decreased in high pH. These changes were maintained as long as a given pH was held. Respiratory changes observed under these conditions were characterized by alterations in both respiratory frequency and magnitude. When the CO2 level of the superfusion fluid was altered, maintaining constant pH by modified HCO3-concentrations, respiratory activity increased at high PCO2 and decreased at low PCO2. These changes were transient and lasted only for a few minutes after exposure to a new level of PCO2. Respiratory changes observed under these conditions were characterized by alterations in magnitude but not in frequency. At constant PCO2 an increase in the HCO3-concentration occasionally enhanced the magnitude of respiration before respiratory activity was depressed by the increased pH. This suggests that HCO3- may act independently as a stimulus to the central chemoreceptor. It is concluded that the mammalian central chemoreceptor for respiratory control is responsive independently to H+ and CO2 and that H+ and CO2 exert differential effects on the respiratory centre in terms of frequency and magnitude. It is suggested that frequency modulation and magnitude (tidal volume) modulation for respiratory control are triggered at different regions in the respiratory centre and/or rely on different mechanisms.

Animals↗
PubMed1985

In vitro and in vivo antibacterial activities of carumonam (AMA-1080), a new N-sulfonated monocyclic beta-lactam antibiotic.

The in vitro and in vivo antibacterial activities of carumonam (AMA-1080), a synthetic sulfazecin derivative, were compared with those of aztreonam, cefoperazone, ceftazidime, and cefsulodin. Carumonam was highly active in vitro against members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus influenzae and weakly active against Streptococcus pneumoniae, but it was not active against Staphylococcus aureus. The MICs of carumonam for 90% of 1,156 clinical Enterobacteriaceae isolates were between 0.013 and 25 micrograms/ml, which were the lowest MICs of the antibiotics tested. The MIC of carumonam for 90% of Klebsiella oxytoca was 0.2 micrograms/ml, whereas that of aztreonam was 50 micrograms/ml. The superiority of carumonam to aztreonam and the reference cephalosporins was also demonstrated by their activities against Klebsiella pneumoniae and Enterobacter cloacae. The MIC of carumonam for 90% of P. aeruginosa was 12.5 micrograms/ml, which was comparable to the MICs of aztreonam and ceftazidime. Carumonam showed a high affinity for the penicillin-binding protein 3 of gram-negative bacteria, but not for the penicillin-binding proteins of S. aureus and Bacteroides fragilis. Carumonam was resistant to hydrolysis by 12 plasmid-mediated beta-lactamases and 7 chromosomal beta-lactamases. It was more stable than aztreonam to hydrolysis by the beta-lactamase of K. oxytoca; this stability is related to the superiority of the in vitro and in vivo activities of carumonam to those of aztreonam against this species. In general, the protective activities (50% effective dose) of carumonam and reference antibiotics in mice with experimental intraperitoneal infections correlated with the in vitro activities (MIC); carumonam showed excellent protective activity against most aerobic gram-negative bacteria.

Animals↗
PubMed1985

Low-threshold, slow-inactivating Na+ potentials in the cockroach giant axon.

Electrophysiological properties of the ventral giant axon in the abdominal nerve cord of the cockroach were studied by recording intracellular potentials following partial or complete block of the K+ conductance. When the K+ conductance was completely blocked by tetraethylammonium (TEA) and 3,4-diaminopyridine, the intensity of depolarizing currents necessary for eliciting the action potential was markedly decreased, and the action potential was followed by a prolonged plateau potential. During the plateau potential following the spike, the input resistance was significantly reduced. The plateau potential was not affected by changing the external Ca2+ concentration but depended on the external Na+ concentration in a manner expected from the Nernst equation and was blocked by tetrodotoxin (TTX). During the plateau potential, the Na+ conductance responsible for the spike was inactivated, whereas immediately after the plateau potential a newly evoked spike was not followed by a plateau potential, suggesting different inactivation kinetics between the spike and plateau Na+ conductances. When the K+ conductance was partially blocked by TEA alone, slow depolarizing responses were evoked at voltage levels a few millivolts more positive than the resting potential. The "threshold" for the slow potential was much lower than that for the spike potential. The slow potential produced after partial block of the K+ conductance was not affected by alterations of the external Ca2+ concentration but was blocked by TTX or in a Na+-free solution. Even in normal medium, a small TTX-sensitive depolarizing response was discernible. This response was similar in its time course and threshold to the slow potential observed after partial block of the K+ conductance. It is concluded that the cockroach giant axon has two populations of Na+ channels, which can be distinguished by differences in time course and voltage levels for activation and that the slow, low-threshold Na+-dependent potential is largely masked by delayed increases in the K+ conductance under normal conditions. It remains uncertain whether the low-threshold slow potential and the plateau potential originate from the same or different populations of Na+ channels.

4-Aminopyridine↗
PubMed1985

Interactions of formylamino- and methoxy-substituted beta-lactam antibiotics with beta-lactamases.

Cephem and nocardicin-type monocyclic beta-lactam antibiotics with a formylamino substituent were highly resistant to hydrolysis by both penicillinases and cephalosporinases. Among antibiotics with a methoxy substituent, an N-sulfonated monocyclic beta-lactam antibiotic, sulfazecin was resistant to beta-lactamases, but cephem antibiotics were sensitive to the cephalosporinase of Enterobacter cloacae. The resistance of the antibiotics to the beta-lactamases depended primarily on the presence of the substituent, but affinity for the beta-lactamases was affected not only by the substituent but also by the presence of other side chains. Formylamino compounds and sulfazecin were as good inducers of beta-lactamases as semisynthetic 7-methoxycephalosporins, but naturally occurring 7-methoxycephalosporins were poor inducers. The inducer activities of the antibiotics were not necessarily related to their beta-lactamase stabilities. The stabilities of the compounds to the beta-lactamases were well reflected in their antibacterial activities against beta-lactamase producing bacteria.

Anti-Bacterial Agents↗
PubMed1985

A physiological study on acetylcholine receptor expressed in Xenopus oocytes from cloned cDNAs.

Nicotinic ACh receptor was expressed in Xenopus oocytes by injecting mRNAs produced from cloned cDNAs encoding the four subunits of ACh receptor of Torpedo californica. ACh responses recorded from oocytes 3 days after injection of the mRNAs were reversibly blocked by d-tubocurarine (1-2 microM), indicating that the newly synthesized receptor is of nicotinic type. The reversal potential of ACh response was found at around -1 - -5 mV. The reversal potential was not changed by removal of extracellular C1-, suggesting that the ionic channel of the newly expressed ACh receptor is permeable only to cations. Repetitive applications of ACh caused desensitization of the receptor. The rate of the desensitization was greater when the membrane potential was more negative. Subunit deletion studies showed that all four subunits are required for the formation of ACh receptors with normal ACh sensitivity. However, ACh receptors without delta subunit responded to ACh with low sensitivity. Studies on ACh receptor mutants with -subunits altered by site directed mutagenesis of the cDNA suggest that the anphipathic segment is involved in the channel function of the receptor as well as the four hydrophobic segments since partial deletion of amino acids in these segments essentially abolished ACh sensitivity with relatively little change in 125I-alpha-bungarotoxin binding activity.

Animals↗
PubMed1985

Calcium dependence of membrane sealing at the cut end of the cockroach giant axon.

Following transection of a nerve fiber, the ruptured membrane must be resealed before regeneration from the proximal cut end. However, it is not certain how fast the cut end is resealed or how it is resealed. We have examined the membrane sealing process following transection of the cockroach giant axon, using recovery of decreased membrane potential and input resistance as criteria. The cable analysis and the injury current profile measured under voltage clamp suggested that the injured site is resealed by a structure with high electrical resistances 5 to 30 min after the transection. This recovery of membrane properties roughly coincided in time with the appearance of a partition-like structure formed near the cut end. The membrane resealing process was highly dependent upon temperature and extracellular Ca2+. Substitution of Ca2+ by equimolar Mg2+, Mn2+, or Sr2+ failed to induce the membrane sealing following transection. However, even in a Ca2+-free solution, the membrane resealing occurred if Ca2+ was injected into the axoplasm near the cut end. Thus, the membrane resealing appears to require Ca2+ entry into the axoplasm. The resealing process was not affected by colchicine or cytochalasin. However, the resealing was prevented by the application of phospholipase A2 inhibitors. These results suggest that the membrane resealing is triggered by phospholipase A2, which is activated by excess Ca2+ entering the axoplasm at the injured site.

Animals↗
PubMed1984

Efferent discharges of sympathetic and parasympathetic nerve fibers during increased intracranial pressure in anesthetized cats in the absence and presence of pressor response.

Efferent discharges of the cervical sympathetic cardiovascular and vagal type 1 fibers in response to increased intracranial pressure (ICP) were simultaneously recorded in cats anesthetized with pentobarbitone and ventilated artificially. Sympathetic outflow of renal nerve fibers was also recorded in some animals. The type 1 fibers were assumed to be cardiac vagal fibers, from the response behavior such a pulse-synchronicity to respiratory and heart rhythm, reflex activation from arterial baroreceptors and reciprocal relationship of the activity to sympathetic ones during slower fluctuations of hemodynamic changes, and which occur spontaneously during Mayer waves. The vagal type 1 discharges increased to various amplitudes with increase in ICP and in the absence and the presence of pressor response. Efferent outflow of the renal and cervical sympathetic fibers frequently decreased with a moderate increase in ICP. There was a slight decrease or no apparent change in the blood pressure, and a higher elevation of ICP ensued. Heart rates decreased with increase in ICP, while the rate frequently increased with levels of ICP over about 120 mm Hg. Changes in the vagal and sympathetic discharges always began at a time before the initiation of cardiovascular response to the elevated ICP. However, when ICP was repeatedly increased, the increase in vagal discharges progressively decayed and was accompanied by vigorous sympathetic firings and a marked pressor response. The sympathetic outflow also decayed following the decrease in vagal activities. The present findings of changes in the vagal type 1 discharges demonstrate clear participation of parasympathetic as well as sympathetic nerve activity in the occurrence of cardiovascular responses to increased ICP. Changes in both these autonomic nerve responses may explain the initial fall in arterial blood pressure and pressor responses associated with bradycardia or tachycardia, at different levels of elevated ICP.

Animals↗
PubMed1984

A hypothesis for neural control of the speed of muscle contraction in the mammal.

A hypothesis for neural control of the contractile properties of muscle is presented. The hypothesis is based on two assumptions: i) the motoneurons innervating both the fast- and slow-twitch muscles in the mammal possess an identical neurotrophic substance which accelerates the speed of muscle contraction, and ii) slow contractions of the slow-twitch muscle are induced by the low frequency discharges of the innervating motoneurons. The presence of such a trophic substance in the motoneurons is supported by the prolongation of contraction time in both the fast- and slow-twitch muscles following denervation. Furthermore, a given slow-twitch muscle dually reinnervated by the fast and slow muscle nerves contracts at the same speed regardless of which nerve is stimulated, if identical neural activity patterns are chronically imposed upon the two nerves. The presence of effective neural activity patterns in the motoneurons innervating the slow-twitch muscle is supported by an increase in the contraction speed of the slow-twitch muscle following virtual elimination of motoneuron activity by transection of the spinal cord. Under such conditions, contraction time of the fast-twitch muscle remains unchanged. Also, cord transection of newborn animals does not affect the postnatal acceleration in contraction time of the fast-twitch muscle, while the postnatal changes of contraction of the slow-twitch muscle mimic those of the fast-twitch muscle. The contraction time of slow-twitch muscle fibers is correlated with the duration of after-hyperpolarization (AHP) in the motoneurons, which regulates the discharge frequency. The duration of AHP increases with age in the motoneurons innervating the slow-twitch muscle but not in those innervating the fast-twitch muscle. It is proposed that the maintenance of slow contractions in the slow-twitch muscle during muscle differentiation is due to the appearance of low frequency discharges in the innervating motoneurons as a result of the postnatal prolongation of the AHP. The implications and limitations of the proposed hypothesis are discussed.

Aging↗
PubMed1983

How a nerve fiber repairs its cut end: involvement of phospholipase A2.

Following transection of a giant axon, the nerve membrane at the cut end is resealed within 5 to 30 minutes. This membrane resealing process is highly dependent upon temperature and extracellular calcium ions. The membrane resealing is triggered by excess calcium entering the axoplasm at the site of transection but is prevented by the application of phospholipase A2 inhibitors. We propose that calcium activated phospholipase A2 plays a central role in resealing of the ruptured nerve membrane.

Acetophenones↗
PubMed1983

Adaptive changes in firing rates in goldfish auditory fibers as related to changes in mean amplitude of excitatory postsynaptic potentials.

Relationship between the firing rate in the auditory fibers and the amplitude of the excitatory postsynaptic potentials (EPSPs) that trigger afferent impulses was investigated. The unitary EPSPs and spike potentials were extracellularly recorded from the goldfish large auditory fibers by means of a microelectrode placed close to the distal terminals. The relation between the firing rate and the amplitude of the EPSPs was studied using a variety of stimulus conditions. The firing probability of phase-locked impulses was linearly related to the mean amplitude of the EPSPs determined for the same time bins. The same linear relation was applicable for the firings elicited by different intensities of sound and observed at various times after onset and also for the firings produced by applying step increments in intensity. The threshold amplitude of the EPSPs required for initiation of afferent impulses was unchanged in these different situations. Random changes in the amplitude of successively evoked EPSPs were found to underlie the probabilistic nature of the sequence of afferent firings. The present results indicate that the per stimulus adaptation and incremental and decremental responses, as observed in the firing probability of afferent impulses, are largely attributable to adaptive changes in the mean amplitude of the evoked EPSPs and not to changes in excitability of the auditory fibers.

Adaptation, Physiological↗
PubMed1983

Synthesis and structure-activity relationships of carbapenems related to C-19393 H2.

By applying the synthetic process reported in our previous paper, we synthesized new carbapenems having various (substituted) thio and alkoxy groups at the C(3) position and 1-hydroxy-1-methylethyl and analogous groups at the C(6) position with cis- and trans-stereochemistry; the in vitro antibacterial and beta-lactamase inhibitory activities of these new carbapenems were examined. Compared to C-19393 H2, some of these compounds (e.g., 11A-a-3 approximately 5) showed improved in vitro antibacterial activity especially against Pseudomonas aeruginosa; they showed a strong beta-lactamase inhibitory activity as well. Two noteworthy effects of substituent variation at the C(6) position on the activities were observed: 1) the trans-configuration caused a definite loss; and 2) introduction of 1-hydroxycyclobutyl and 1-hydroxy-1-methylpropyl groups in place of the 1-hydroxy-1-methylethyl group caused a diminution. The carbapenem (13A-a-2) with an alkoxy group at the C(3) position had a marked decrease in activity compared to the corresponding thio-substituted carbapenem (11A-a-12).

Indicators and Reagents↗
PubMed1982

Sites and mechanisms of action of lidocaine upon the isolated spinal cord of the frog.

The sites of action of lidocaine on the responses evoked by stimulation of lateral column (LC) and dorsal root (DR) were studied in the isolated, intra-arterially perfused spinal cord of the bullfrog. When the ventral root volley produced by stimulation was abolished by lidocaine, the presynaptic focal potential was almost unchanged. Intracellular recordings from motoneurons clearly demonstrated a marked reduction in amplitude of the EPSPs before the block of conduction of presynaptic fibers and the block of invasion of the neuron soma by antidromic spike potential. At low concentrations of lidocaine, the EPSPs elicited by LC stimulation produced shortening in time to peak, slowing in the decay time, decrease in amplitude and smaller changes in the later EPSPs of a train than the earlier ones. From the observations, it was concluded that the low concentrations of lidocaine affected primarily synaptic transmission in the spinal cord. The possible mechanisms of action of lidocaine were discussed.

Animals↗