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Biomedical subjects

R Matsuo

Publications and source records attributed to R Matsuo.

At least 19 recordsLinked to original sources

Noxious tooth pulp stimulation suppresses c-fos expression in the rat hippocampal formation.

Changes in the expression of immediate early gene c-fos by noxious mechanical stimulation to the mandibular incisor pulp of rats were immunohistochemically examined in the hippocampus (Ammon's horn and dentate gyrus) and the retrohippocampus (subiculum, presubiculum, parasubiculum and entorhinal cortex). The highest control levels were found in subiculum, CA1, dentate and deep medial entorhinal cortex. Lower, but substantial levels were present in the other areas. Whereas weak dentinal stimulation caused increases in c-fos expression in some regions which were not statistically significant, strong tooth pulp stimulation caused a bilateral decrease in c-fos expression in every region except contralateral subiculum. These decreases reached statistical significance in superficial layer parasubiculum bilaterally (p<0.01), bilateral CA1 and ipsilateral side of superficial layer of medial entorhinal cortex (p<0.05). We suggest that inhibitory circuitry in hippocampal formation regions may be activated by peripheral noxious somatosensory inputs and this change in activity is accompanied by a change in the expression of the immediate early gene, c-fos.

Animals

Serotonergic modulation of the hyperpolarizing spike afterpotential in rat jaw-closing motoneurons by PKA and PKC.

Intracellular recordings were obtained from rat jaw-closing motoneurons (JCMNs) in slice preparations to investigate the effects of serotonin (5-HT) on the postspike medium-duration afterhyperpolarization (mAHP) and an involvement of protein kinases in the effects. Application of 50 microM 5-HT caused membrane depolarization and increased input resistance in the most cells without affecting the mAHP, whereas not only membrane depolarization and an increase in input resistance, but also the suppression of the mAHP amplitude was induced by higher dose of 5-HT (100 or 200 microM). On the other hand, when the mAHP amplitude was increased by raising [Ca(2+)](o) from 2 to 6 mM, 5-HT-induced attenuation of the mAHP amplitude was enhanced, and even 50 microM 5-HT reduced the mAHP amplitude. This 5-HT-induced suppression of the mAHP could be mimicked by application of membrane-permeable cAMP analogue 8-Bromo-cAMP, potentiated by the cAMP-specific phosphodiesterase inhibitor Ro 20-1724 and antagonized by protein kinase A (PKA) inhibitor H89. The enhancement of the mAHP attenuation induced by 50 microM 5-HT under raised [Ca(2+)](o) was blocked by a protein kinase C (PKC) inhibitor chelerythrine, suggesting an involvement of PKC in this enhancement. On the other hand, the attenuation of the mAHP induced by PKC activator phorbol 12-myristate 13-acetate was blocked almost completely by H89, suggesting that the PKC action on the mAHP requires PKA activation. Neither 5-HT(1A) antagonist NAN-190 or 5-HT(4) antagonist SB 203186 blocked 5-HT-induced attenuation of the mAHP. We conclude that 5-HT induces dose-dependent attenuation of the mAHP amplitude through cAMP-dependent activation of PKA and that PKC-dependent PKA activation is also likely to be involved in the enhancement of 5-HT-induced attenuation of the mAHP under raised [Ca(2+)](o). Because the slope of the linear relationship between firing frequency and injected current was increased only when the mAHP amplitude was decreased by 5-HT, it is suggested that the relation between incoming synaptic inputs and firing output in JCMNs varies according to serotonergic effects on JCMNs and calcium-dependent modulation of its effects.

Animals

Two types of parasympathetic preganglionic neurones in the superior salivatory nucleus characterized electrophysiologically in slice preparations of neonatal rats.

1. The electrophysiological properties of parasympathetic preganglionic neurones in the superior salivatory nucleus were studied in thin- and thick-slice preparations of rats aged 1 and 2 weeks using the whole-cell patch-clamp technique. 2. The superior salivatory neurones were identified by a retrograde tracing method with dextran-tetramethylrhodamine-lysine. The injection of the tracer into the chorda-lingual nerve labelled the neurones innervating the submandibular ganglia and those innervating the intra-lingual ganglia, while the injection into the tip of the tongue labelled the latter group of neurones. 3. Firing characteristics were investigated mainly in the neurones of 6-8 days postnatal rats. In response to an injection of long depolarizing current pulses at hyperpolarized membrane potentials (< -80 mV) under a current clamp, the neurones labelled from the nerve displayed a train of action potentials with either a long silent period preceding the first spike (late spiking pattern) or a long silent period interposed between the first and second spikes (interrupted spiking pattern). The neurones labelled from the tongue invariably displayed the interrupted spiking pattern. 4. Under a voltage clamp, among the neurones from 6-8 days postnatal rats, those labelled from the nerve expressed either a fast or a slow transient outward current (A-current), while those labelled from the tongue invariably showed a slow transient outward current. Both the fast and slow A-currents were largely depressed by 1 mM 4-aminopyridine. 5. Similar fast and slow A-currents were observed in the neurones of rats aged 14-15 days. Both the time to peak and decay time constant of these A-currents were accelerated, suggesting a developmental trend of maturation in the activation and inactivation kinetics between 6 and 15 days postnatal. 6. Based on the differences in the firing pattern and outward current, the superior salivatory neurones can be separated into two distinct types. We discuss the functional aspects of these two types of neurones with reference to their target organs.

Algorithms

Cataloging altered gene expression during rat hippocampal long-term potentiation by means of differential display.

We have employed mRNA differential display (DD) to generate a catalog of cDNAs whose expression in the hippocampus was regulated during long-term potentiation (LTP) in dentate gyrus of anesthetized rats. DD with 459 combinations of primer pairs revealed that 80 out of approximately 70000 bands displayed showed a reproducible change in their expression level. These cDNAs were categorized into seven groups according to changes in their temporal expression pattern. Some of these cDNAs were induced rapidly, but transiently, after the LTP induction, some induced rapidly and persistently, some induced slowly, and some down-regulated following LTP. This suggests that a complex molecular hierarchy underlies the maintenance of hippocampal LTP.

Animals

Neural activity of the superior salivatory nucleus in rats.

We recorded the neural activity of the superior salivatory (SS) neurons in brain slice preparations from neonatal rats in vitro and in decerebrate anesthetized rats in vivo. In the in vitro experiment, the SS neurons were retrogradely labeled by the injection of Rhodamine into the chorda-lingual nerve (labeling SS neurons innervating the submandibular and intra-lingual ganglia) or into the anterior part of the tongue. The SS neurons labeled from the nerve were classifiable into two types: Type-I, tonic firing at a frequency of up to 30 Hz; and Type-II, phasic firing at a higher frequency of up to 70 Hz followed by tonic firing at 30-50 Hz. All of the SS neurons labeled from the tongue were Type-II. Since the anterior tongue is a non-glandular area, the type of cells may be involved in vasodilatation. Type-I neurons, which did not innervate the tongue, may be responsible for salivation. In the in vivo experiment, the reflex activity evoked by taste or mechanical stimulation was recorded from the axons of the SS neurons innervating the submandibular ganglia. These fibers also displayed two firing patterns. One was a tonic firing pattern discharging at 5-30 Hz. The other consisted of a transient firing (about 80 Hz) at the beginning of stimulation and then a prolonged firing at 5-40 Hz. The latter firing pattern was similar to that of the Type-II neurons. These findings suggest that the parasympathetic nerves of the salivary glands contain both the secretory- and vasodilator-type of SS neuron.

Action Potentials

Role of submandibular and sublingual saliva in maintenance of taste sensitivity recorded in the chorda tympani of rats.

1. To evaluate the role of saliva in the maintenance of taste sensitivity, the activities in the rat chorda tympani innervating taste buds in the anterior part of the tongue were analysed. The effects of chronic extirpation of the submandibular and sublingual salivary glands were tested and compared with results after chronic oral administration of artificial saliva. 2. Removal of the salivary glands sharply decreased chorda tympani responses to four different taste stimuli by 7 days post-desalivation, while a stable response to cold water was observed by at least 28 days. 3. This selective decrease in taste responses was considerably recovered by 7-day-oral injection of artificial saliva (containing NaHCO3, KCl and/or mucin) or distilled water. However, the injection of the salt-containing artificial saliva induced significantly larger sucrose and smaller NaCl, HCl and quinine responses than did the injection of distilled water. 4. In our salivary manipulations, an alteration in the number of the functional sweet receptors was suggested by the cross-adaptation technique using NaHCO3, whereas sensitivity to the epithelial sodium transport blocker, amiloride, was stable in the NaCl response. 5. Salivary water and electrolytes which may participate in forming the external environment of the taste receptor cells modulated taste sensitivity in the chorda tympani.

Adaptation, Physiological

CD4- CD8- TCR alpha/beta+ suppressor T cells demonstrated in mice 1 day after thermal injury.

We have described previously that CD8+ CD11b+ TCR gamma/delta+ type 2 T cells (BA-type 2 T cells) and suppressor macrophages (Sup-Mł) are generated in spleens of mice 3 to 5 days (Sup-Mł) and 4 to 9 days (BA-type 2 T cells) after thermal injury. In the present study, an additional suppressor T cell, characterized as CD3+ CD4- CD8- TCR alpha/beta+ T cells (double negative suppressor T cells, DN Sup-T cells), was demonstrated in mice 1 day after thermal injury. DN Sup-T cells inhibited the proliferation of lymphocytes stimulated with allogeneic cells or a lectin in a mixed lymphocyte reaction, and produced both type 1 and type 2 cytokines (interferon-gamma, interleukin-2, interleukin-4, and interleukin-10) when they were stimulated in vitro with anti-CD3 monoclonal antibody. These results suggest that DN Sup-T cells express phenotypic properties similar to natural suppressor cells and cytokine-producing profiles different from type 1 (Th1 cells and CTLs) and type 2 T cells (Th2 cells and CD8+ type 2 T cells). DN Sup-T cells may play a role on the burn-associated immunosuppression appearing in the acute phase of thermally injured individuals.

Animals

Modulation of jaw muscle spindle discharge during mastication in the rabbit.

Discharges of jaw muscle spindles were recorded during chewing carrot from mesencephalic trigeminal nucleus (Mes V) in the awake rabbit to evaluate contribution of the muscle spindles to the development of complete sequences of masticatory movements. The Mes V spindle units were divided into two types according to the maximum firing rates during mastication, with a dividing line at 200 Hz; high-frequency units and low-frequency units. Although both types of units fired maximally during the jaw-opening phase of chewing cycles, their firing rates and pattern varied according to three sequential stages of mastication (stages I, IIa, and IIb). The high-frequency units often increased firing before the start of mastication and built up firing in the first few chewing cycles. Their maximal firing rate was sometimes lower during stage IIa (chewing stage) than during stage I (ingestion stage) and stage IIb (preswallowing stage), although the jaw movements were greater in stage IIa than in other stages. The phase relationship of the firing to a jaw movement cycle in stage IIa was consistent in individual units. The low-frequency units did not build up activity before the onset of movements. They fired mostly during the jaw-opening phase, but the peak of firing did not necessarily coincide with the time of maximal opening. It was concluded that the difference in the firing pattern among masticatory stages may be ascribed to a stage-dependent modulation of both fusimotor activity and jaw movement pattern.

Animals

Regulation of masticatory force during cortically induced rhythmic jaw movements in the anesthetized rabbit.

To examine the relationships between masticatory force, electromyogram (EMG) of masticatory muscles, and jaw movement pattern, we quantitatively evaluated the effects of changing hardness of a chewing substance on these three variables. Cortically induced rhythmic jaw movements of a crescent-shaped pattern were induced by electrical stimulation of the cerebral cortical masticatory area in the anesthetized rabbit. The axially directed masticatory force was recorded with a small force-displacement transducer mounted on the ground surface of the lower molars. EMGs were recorded from the masseter and digastric muscles simultaneously with jaw movements. Five test strips of polyurethane foam of different hardness were prepared and inserted between the upper molar and the transducer during the movements. The peak, impulse, and buildup speed of the masticatory force increased with strip hardness, whereas duration of the exerted force did not vary with strip hardness. The integrated activity and duration of the masseteric EMG bursts also increased with strip hardness. The integrated EMG activity of the digastric bursts was weakly related to strip hardness, whereas the duration was not. The minimum gape increased with strip hardness, but the maximum gape did not. The horizontal excursion of the jaw did not vary in a hardness-dependent manner, although it was greater in the cycles with strip application than in the cycles without strip application. Deprivation of periodontal sensation by cutting the nerves to the teeth reduced the buildup speed of the force, maximum gape, net gape, and horizontal jaw movements. The denervation also elongated the force duration and that of masseteric EMG bursts. However, the rate of the hardness-dependent changes in the above parameters did not alter after denervation. The latency of the masseteric EMG response to strip application was evaluated before and after denervation. In both conditions, it was > or = 6 ms in approximately 70% of the cycles and <6 ms in the remaining approximately 30%, which cannot be explained by a simple reflex mechanism. On the basis of the analysis of correlation coefficients, the masseteric integrated EMG seemed to be a good indicator of the peak and impulse of the masticatory force both before and after denervation. We conclude that periodontal afferents would be responsible for a quick buildup of masticatory force and that afferents other than those from periodontal tissue would contribute to the hardness-dependent change of masticatory force during cortically induced rhythmic jaw movements.

Animals

Role of calcium conductances on spike afterpotentials in rat trigeminal motoneurons.

Intracellular recordings were obtained from rat trigeminal motoneurons in slice preparations to investigate the role of calcium conductances in the depolarizing and hyperpolarizing spike afterpotential (ADP and mAHP, respectively). The mAHP was suppressed by bath application of 1 microM apamin, 2 mM Mn2+, and 2 mM Co2+, and also by intracellular injection of ethylene glycol-bis(b-aminoethylenether)-N,N,N',N'-tetraacetic acid (EGTA), suggesting that the potassium conductance generating the mAHP is activated by Ca2+ influx. Mn2+ (2 mM) or Cd2+ (500 microM) reduced the ADP, whereas the ADP amplitude was increased by raising extracellular Ca2+ concentration from 2 to 8 mM by bath application of Ba2+ (0.5-5 mM) and by intracellular injection of EGTA. This would suggest that Ca2+ itself is likely to be the charge carrier generating the ADP. Focal application of omega-conotoxin GVIA (10-30 microM) suppressed the mAHP and enhanced the ADP, whereas focal application of omega-agatoxin IVA (10-100 microM) reduced the ADP amplitude without apparent effects on the mAHP. We conclude that Ca2+ influx through omega-agatoxin IVA-sensitive calcium channels is at least in part responsible for the generation of the ADP and that Ca2+ influx through omega-conotoxin GVIA-sensitive calcium channels contributes to the generation of the mAHP. Because of the selective suppression of the ADP and mAHP by omega-agatoxin IVA and omega-conotoxin GVIA, respectively, it is suggested that both calcium channels are separated geometrically in rat trigeminal motoneurons.

Animals

[Efficacy and safety of intramuscular imipenem/cilastatin (IPM/CS) for complicated urinary tract infections].

An intramuscular preparation of imipenem/cilastatin (IPM/CS, 500 mg/500 mg) was administered to 59 patients with complicated urinary tract infections (UTI; cystitis and pyelonephritis) to evaluate its efficacy and safety. The obtained results are summarized as follows: In patients with cystitis, evaluations based on daily frequencies of administration were also performed. 1) According to the treating doctors, the drug showed an overall efficacy rate of 80% (45/56 patients). The efficacy rate was 89% in patients with cystitis treated by a u.i.d. regimen. Among patients treated by a b.i.d. regimen, the efficacy rate was 67% for cystitis cases and 84% for pyelonephritis cases. 2) When clinical efficacy was assessed according to the criteria for UTI drug efficacy evaluation, the drug was 'markedly effective' in 14 patients, 'effective' in 23, and ineffective in 11 patients, for an efficacy rate of 77% (37/48 patients). 3) The microbiological eradication rate was 88% (59/67 strains). The rate was 95% (20/21 strains) for Gram-positive bacteria and 85% (39/46 strains) for Gram-negative bacteria. The efficacy for Enterobacter faecalis and Pseudomonas aeruginosa was 100% and 73%, respectively. 4) As side effects, pain at the injection site was reported by one patient and abnormal laboratory test values were observed in 2 patients. All of these reactions were mild and resolved shortly after the completion of treatment. Based on these findings, it is concluded that this intramuscular preparation of IPM/CS is effective for treating complicated urinary tract infections.

Adolescent

Interleukin-12 protects thermally injured mice from herpes simplex virus type 1 infection.

Severe burn injury is associated with increased susceptibility to severe herpesvirus infections. Type 2 cytokines [interleukin (IL)-4 and IL-10] released from burn-associated CD8+ type 2 T cells (BA-type 2 T cells) have been shown to play a role in the increased susceptibility of thermally injured mice (TI-mice) to herpes simplex virus type 1 (HSV-1) infection. Because IL-12 has been shown to inhibit the generation of type 2 T cells, murine rIL-12 was injected into TI-mice exposed to HSV-1 to determine whether IL-12 could influence HSV-1 infections in individuals bearing type 2 T cells. rIL-12 improved the resistance of TI-mice or mice inoculated with T6S cells (a BA-type 2 T cell clone) against HSV-1 infection. Type 2 cytokines were detected in sera of TI-mice or mice inoculated with T6S cells (T6S-mice). However, treatment of TI-mice or T6S-mice with rIL-12 inhibited type 2 cytokine production in the sera of these mice. All TI-mice exposed to a lethal dose of HSV-1 survived when they were treated with a mixture of monoclonal antibodies (mAbs) against type 2 cytokines. Staphylococcal enterotoxin A [an interferon-gamma (IFN-gamma) inducer] stimulated serum IFN-gamma production in TI-mice and T6S-mice treated with rIL-12, whereas no IFN-gamma was produced in mice treated with saline. These results suggest that IL-12 has the potential to protect TI-mice infected with a lethal dose of HSV-1 via a shift to type 1 T cell responses from type 2 T cell responses.

Animals

[MR imaging of hepatocellular carcinoma following microwave coagulation therapy].

MRI was performed in 13 patients who had microwave coagulation therapy (MCT) for hepatocellular carcinoma. Six of them underwent surgery after MRI. The area (including tumor) treated by MCT showed low to high intensity on T1WI, and low to isointensity on T2WI. No enhancement was obtained on dynamic MRI. Histologically, this area was supposed to be coagulation necrosis. On T1WI, only tumor showed high intensity within the MCT area in 8 patients, and nearly uniform intensity was observed in 5 patients. Histologically, residual cell nuclei were observed in the former, and nearly uniform coagulation necrosis in the latter. The marginal part of the MCT area exhibited low intensity on T1WI, and high intensity on T2WI. Strong enhancement was obtained on dynamic MRI, and histologically, granulation tissue was noted. In the hepatic parenchyma around the MCT area, a ring-or wedge-shaped high intensity part was observed in 7 patients on T2WI, and that part was enhanced on dynamic MRI. This finding was considered to reflect changes such as hepatic hyperperfusion. In terms of the capability of visualizing residual tumor after MCT, MRI was superior to CT. Furthermore, a clear distinction was seen between the MCT area and non-MCT area on T2WI and dynamic MRI. Thus, MRI was useful in the determination of additional therapy.

Aged

Neural activity of chorda tympani mechanosensitive fibers during licking behavior in rats.

The chorda tympani nerve, supplying the anterior two-thirds of the tongue, contains gustatory and mechanosensitive afferent fibers. We have analyzed discharge patterns in rats of various fibers recorded from dissected nerve filaments during licking behavior of which 4 were taste-sensitive and 12 mechanosensitive. The incidence of these two types were estimated electrophysiologically under anesthesia and their conduction velocity measured. Recordings in freely moving animals showed that the mechanosensitive fibers innervating the dorsal part of the tongue gave two burst discharges per lick, suggesting that contact of the tongue with the upper incisors and/or lip occurred during tongue protrusion and retraction. The fibers from the tip of the tongue showed one burst discharge per lick, which was the response to contact with a drinking spout. No rhythmical discharges synchronized with lick signals were observed in the fibers from the lateral part of the tongue or the taste-sensitive fibers. Such mechanoreceptor discharges were difficult to detect in recordings from the whole chorda tympani nerve. This masking of responses was due mainly to activation of a small number of mechanosensitive fibers by licking-induced mechanical stimulation. The lubricating action of saliva also decreased mechanoreceptor sensitivity. Despite their small number, the mechanosensitive fibers had axons with faster conduction velocities (larger diameter) than the taste-sensitive fibers. This was probably the reason why dissected nerve bundles more frequently showed mechanical than taste responses in conscious rats.

Action Potentials

Prolonged incubation with neuropeptide Y upregulates beta-adrenoceptors yet does not cause supersensitivity of beta-adrenoceptor signaling.

In neonatal rat ventricular myocytes prolonged incubation with 1 microM neuropeptide Y (2 h-48 h) increased beta-adrenoceptor density 16-24% (n = 4--8, all p < 0.05), an effect prevented by pertussis toxin pretreatment. Prolonged incubation with neuropeptide Y had no effect on adenylycylclase activity stimulated by 5'-guanylylimidodiphosphate or (-)-isoprenaline, probably because of a neuropeptide Y-induced decrease in affinity of the beta-adrenoceptor for agonist. Thus, chronic incubation with an inhibitory agonist does not inevitably lead to supersensitivity of the adenylylcyclase pathway.

Adenylyl Cyclases

Inhibitory effect of sympathetic stimulation on activities of masseter muscle spindles and the jaw jerk reflex in rats.

1. To evaluate sympathetic effects on jaw muscles, the discharges of masseter muscle spindle afferents, jaw muscle electromyographic (EMG) activities and blood flow changes were compared in anaesthetized decerebrate rats before and during electrical stimulation of the cervical sympathetic trunk. 2. To eliminate the possibility of efferent control from the trigeminal motoneurones, muscle spindle activity was recorded from the cut peripheral end of the masseter nerve. The absence of a sympathetic component in the masseter nerve was confirmed by the horseradish peroxidase method. 3. Electrical stimulation of the sympathetic nerve at frequencies within the physiological range reduced muscle spindle afferent discharges evoked by passive jaw opening. 4. Sympathetic stimulation also reduced the EMG activity evoked by the jaw jerk reflex, which may reflect a sympathetic effect on spindle afferents. After cessation of stimulation, a transient increase in EMG activity was observed, which may be due to efferent supply from the trigeminal motoneurones. During rhythmical jaw movements, no sympathetic effect on EMG activity was detected. 5. The above sympathetic effect on muscle spindle afferents and EMG activity was independent of blood flow changes.

Action Potentials

Decreased mitogenic and osteogenic responsiveness of calvarial osteoblasts isolated from aged rats to basic fibroblast growth factor.

Osteoporosis seen in aged individuals is represented by the reduced bone mass most likely resulting from decreased bone formation by osteoblasts. To examine whether aging causes a decrease in osteoblast activity, calvarial osteoblasts were isolated from aged rats (AOB) and studied for the capacity of the cells to form mineralized bone-like nodules in comparison with that of fetal calvarial osteoblasts (FOB). There were no significant differences in basal mineralized bone-like nodule formation determined by quantifying the size of the nodules which were formed in the cultures of AOB and FOB. However, the responsiveness of AOB to growth factors was profoundly reduced. AOB showed only marginal increase in mineralized bone-like nodule formation and growth in response to basic fibroblast growth factor (bFGF). On the other hand, bFGF markedly promoted mineralized bone-like nodule formation and proliferation in FOB. These results suggest that decreased responsiveness to local osteotropic growth factors such as bFGF might account for the reduced bone formation by aged osteoblasts, which in turn leads to the loss of bone mass characteristic for senile osteoporosis.

Aging

[Treatment of refractory hypoxemia due to right-to-left interatrial shunt complicating right ventricular infarction: successful short-term percutaneous catheter closure of the patent foramen ovale].

Refractory hypoxemia as a complication of right ventricular infarction is rare. A 74-year-old man developed persistent hypoxemia due to right-to-left interatrial shunting through a patent foramen ovale during the acute phase of right ventricular infarction. Short-term percutaneous transvenous closure of the patent foramen ovale with a large balloon occlusion catheter was life-saving.

Aged