Biomedical subjects

I Homma

Publications and source records attributed to I Homma.

At least 19 recordsLinked to original sources

PubMed2001

The effect of anticipatory anxiety on breathing and metabolism in humans.

Respiratory patterns are influenced by cortical and limbic factors and generated by a complex interaction between metabolic requirements and their behavioral effects. Our previous results showed that the temporal pole and the amygdala in the limbic system are related to anxiety and associated with an increase of respiratory frequency, especially in high trait anxiety subjects. The purpose of this study was to investigate the relationship between respiratory patterns and metabolic output during the production of anticipatory anxiety. In all subjects, fR increased without changes in V(O(2)), V(CO(2)) and HR; and PET(CO(2)) decreased during anticipatory anxiety. In the subjects with high trait anxiety, the increase of fR and the decrease of TE were larger than those in the subjects with low trait anxiety. These results suggest that an increase in respiratory frequency is not related to metabolic factors and is consistent with a mechanism involving the limbic system modulating respiratory drive.

Adult↗

PubMed2001

Comparison of source localization of interictal epileptic spike potentials in patients estimated by the dipole tracing method with the focus directly recorded by the depth electrodes.

The purpose of the study was to investigate the accuracy of location of equivalent current dipoles estimated by the dipole tracing method (DT) utilizing a realistic 3-shell (scalp-skull-brain) head model (SSB-DT). Three patients with intractable complex partial seizures, diagnosed as having typical temporal seizures were investigated. We recorded the interictal spike potentials with surface electrodes (International 10/20 system) and with intracerebral depth electrodes simultaneously. We compared the location of dipoles of the spikes estimated by the SSB-DT with the focus of the spikes determined by the recording from the depth electrodes. We found that the location of the dipoles estimated by SSB-DT corresponded to the location of the depth electrodes, which could record the epileptic spikes. This finding proved that SSB-DT is reliable and valid for estimating neural activity in deep locations such as the limbic system.

Action Potentials↗

PubMed2001

Involvement of central histaminergic neurons in polypnea induced by hyperthermia in rabbits.

A role of central histamine in the preoptic area/anterior hypothalamus (POA/AH) for the regulation of hyperthermia-induced polypnea was examined in anesthetized, paralyzed, vagotomized and artificially ventilated rabbits. Phrenic nerve activities were recorded to monitor respiratory neuronal output. Hyperthermia increased respiratory frequency by reductions of inspiratory time (T(I)) and expiratory time (T(E)). Pyrilamine, an H1 receptor antagonist, which was applied to the POA/AH reduced polypnea under hyperthermia. The effect of S+alpha-fluoromethylhistidine, a specific inhibitor of histidine decarboxylase, applied in a lateral ventricle was comparable to the effect of pyrilamine on polypnea. Moreover, histamine dihydrochloride applied into the POA/AH at a normal body temperature produced polypnea by reductions of T(I) and T(E). The results suggest that central histamine in the POA/AH contributes to the generation of polypnea in hyperthermia through H1 receptors.

Animals↗

PubMed2001

Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice.

Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically chemoattracts CC chemokine receptor 4-positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhibit the induction of asthmatic reaction in mice elicited by OVA. TARC was constitutively expressed in the lung and was up-regulated in allergic inflammation. The specific Ab against TARC attenuated OVA-induced airway eosinophilia and diminished the degree of airway hyperresponsiveness with a concomitant decrease in Th2 cytokine levels. Our results for the first time indicate that TARC is a pivotal chemokine for the development of Th2-dominated experimental allergen-induced asthma with eosinophilia and AHR. This study also represents the first success in controlling Th2 cytokine production in vivo by targeting a chemokine.

Animals↗

PubMed2001

Neuronal histamine release elicited by hyperthermia mediates tracheal dilation and pressor response.

Whether brain histaminergic neurons contribute to the regulation of tracheal tone and peripheral vascular tone under hyperthermia was investigated in anesthetized rabbits. Histamine release from the rostral ventrolateral medulla (RVLM), the raphe nuclei, and the solitary nucleus of the medulla oblongata was significantly increased by hyperthermia. The increased histamine was significantly suppressed by 10(-6) M tetrodotoxin microdialyzed in each area. Tracheal pressure and mean arterial pressure were significantly decreased and increased by hyperthermia, respectively. An H(1)-receptor antagonist, 5 x 10(-6) M (+)-chlorpheniramine, bilaterally microdialyzed in the RVLM significantly enhanced histamine release in the RVLM as well as significantly suppressed tracheal dilation and pressor response caused by hyperthermia. These data indicate that histamine release in the medulla oblongata is enhanced by hyperthermia. The enhanced histamine is the neuronal origin and the cause of tracheal dilation and pressor response at least via H(1) receptors in the RVLM. Brain histaminergic neurons play important roles in tracheal tone and peripheral vascular tone via H(1) receptors in the RVLM and homeostasis on body temperature.

Animals↗

PubMed2000

Lack of temperature-induced polypnea in histamine H1 receptor-deficient mice.

Breathing patterns are influenced by body temperature. However, the central mechanism for changes of breathing patterns is unknown. We previously showed that central histamine contributed to temperature-induced polypnea in mice (Izumizaki, M., Iwase, M., Homma, I., Yanai, K., Watanabe, T. and Watanabe, T., Central histamine contributed to the temperature-induced polypnea in mice, Neurosci. Res., 23 (1999) S282). In this study we examined the role of central histamine H1 receptors in temperature-induced polypnea using wild and mutant mice lacking histamine H1 receptors. Breathing patterns were characterized at two different body temperatures during hypercapnia under conscious conditions. In wild mice a raised body temperature increased respiratory frequency mainly due to a reduction in expiratory time, whereas in mutant mice respiratory frequency did not increase even though the body temperature was elevated. These results indicate that central histamine contributes to an increase in respiratory frequency due to a reduction in expiratory time through histamine H1 receptors when body temperature is raised.

Animals↗

PubMed2000

The source generator of respiratory-related anxiety potential in the human brain.

In this study, we used the dipole tracing method of a scalp-skull-brain head model to determine the location of the electric current source which correlates with the increased respiratory rate due to anxiety in humans. Anticipatory anxiety was produced by giving electrical stimulation to the left forefinger after the warning red light. While administering anticipatory anxiety, subjects' anxiety state and respiratory rates increased. In averaged electroencephalogram, which was triggered by onset of inspiration, positive waves were observed approximately 350 ms after the onset of inspiration. In this period of time, dipoles were concentrated in the right temporal pole, and the temporal pole and the amygdala in the most anxious subject. This data suggests that there are respiratory-related neural activities in limbic and paralimbic areas which may correlate with anxiety in humans.

Amygdala↗

PubMed2000

Central histamine contributed to temperature-induced polypnea in mice.

Breathing pattern is influenced by body temperature. However, the central mechanism for changing breathing patterns is unknown. Central histamine is involved in heat loss mechanisms in behavioral studies, but little is known about its effect on breathing patterns. We examined first the effect of body temperature on breathing patterns with increasing hypercapnia in conscious mice and then that of the depletion of central histamine by S(+)-alpha-fluoromethylhistidine hydrochloride (alpha-FMH) (100 mg/kg ip), a specific inhibitor of histidine decarboxylase, at normal and raised body temperatures. A raised body temperature increased respiratory frequency with reductions in both inspiratory and expiratory time and decreased tidal volume. On the other hand, alpha-FMH lowered respiratory frequency with a prolongation of expiratory time at the raised temperature; however, this was not observed at a normal temperature. These results indicate that central histamine contributes to an increase in respiratory frequency as a result of a reduction in expiratory time when body temperature is raised.

Algorithms↗

PubMed2000

Thixotropy of rib cage respiratory muscles in normal subjects.

In this study, we searched for signs of thixotropic behavior in human rib cage respiratory muscles. If rib cage respiratory muscles possess thixotropic properties similar to those seen in other skeletal muscles in animals and humans, we expect resting rib cage circumference would be temporarily changed after deep rib cage inflations or deflations and that these aftereffects would be particularly pronounced in trials that combine conditioning deep inflations or deflations with forceful isometric contractions of the respiratory muscles. We used induction plethysmography to obtain a continuous relative measure of rib cage circumference changes during quiet breathing in 12 healthy subjects. Rib cage position at the end of the expiratory phase (EEP) was used as an index of resting rib cage circumference. Comparisons were made between EEP values of five spontaneous breaths immediately before and after six types of conditioning maneuvers: deep inspiration (DI); deep expiration (DE); DI combined with forceful effort to inspire (FII) or expire (FEI); and DE combined with forceful effort to inspire (FIE) or expire (FEE), both with temporary airway occlusion. The aftereffects of the conditioning maneuvers on EEP values were consistent with the supposition that human respiratory muscles possess thixotropic properties. EEP values were significantly enhanced after all conditioning maneuvers involving DI, and the aftereffects were particularly pronounced in the FII and FEI trials. In contrast, EEP values were reduced after DE maneuvers. The aftereffects were statistically significant for the FEE and FIE, but not DE, trials. It is suggested that respiratory muscle thixotropy may contribute to the pulmonary hyperinflation seen in patients with chronic obstructive pulmonary disease.

Adult↗

PubMed1999

Movement related cortical source for elbow flexion in patients with branchial plexus injury after intercostal-musculocutaneous nerve crossing.

Nine patients with brachial plexus injury whose transected musculo-cutaneous nerves had been sutured with intercostal nerves were examined and the relationship between flexion of the operated elbow and the respiratory movement were shown. Three out of nine patients showed independent control of movement from respiration after regeneration. The primary motor cortex for either flexion of the elbow to the operated side or brisk voluntary inspiration was estimated in the medial vertex region of the frontal cortex by the dipole-tracing method in these three patients. The present results suggest that patients contract the biceps muscle reinnervated by the intercostal nerve independently from respiratory movements using the same primary motor cortex with trunk movements. Functional plasticity may occur in the patients using the primary trunk motor cortex for elbow flexion.

Adolescent↗

PubMed1999

Respiratory network function in the isolated brainstem-spinal cord of newborn rats.

The in vitro brainstem-spinal cord preparation of newborn rats is an established model for the analysis of respiratory network functions. Respiratory activity is generated by interneurons, bilaterally distributed in the ventrolateral medulla. In particular non-NMDA type glutamate receptors constitute excitatory synaptic connectivity between respiratory neurons. Respiratory activity is modulated by a diversity of neuroactive substances such as serotonin, adenosine or norepinephrine. Cl(-)-mediated IPSPs provide a characteristic pattern of membrane potential fluctuations and elevation of the interstitial concentration of (endogenous) GABA or glycine leads to hyperpolarisation-related suppression of respiratory activity. Respiratory rhythm is not blocked upon inhibition of IPSPs with bicuculline, strychnine and saclofen. This indicates that GABA- and glycine-mediated mutual synaptic inhibition is not crucial for in vitro respiratory activity. The primary oscillatory activity is generated by neurons of a respiratory rhythm generator. In these cells, a set of intrinsic conductances such as P-type Ca2+ channels, persistent Na+ channels and G(i/o) protein-coupled K+ conductances mediates conditional bursting. The respiratory rhythm generator shapes the activity of an inspiratory pattern generator that provides the motor output recorded from cranial and spinal nerve rootlets in the preparation. Burst activity appears to be maintained by an excitatory drive due to tonic synaptic activity in concert with chemostimulation by H+. Evoked anoxia leads to a sustained decrease of respiratory frequency, related to K+ channel-mediated hyperpolarisation, whereas opiates or prostaglandins cause longlasting apnea due to a fall of cellular cAMP. The latter observations show that this in vitro model is also suited for analysis of clinically relevant disturbances of respiratory network function.

Animals↗

PubMed1999

Expiratory time determined by individual anxiety levels in humans.

We have previously found that individual anxiety levels influence respiratory rates in physical load and mental stress (Y. Masaoka and I. Homma. Int. J. Psychophysiol. 27: 153-159, 1997). On the basis of that study, in the present study we investigated the metabolic outputs during tests and analyzed the respiratory timing relationship between inspiration and expiration, taking into account individual anxiety levels. Disregarding anxiety levels, there were correlations between O2 consumption (VO2) and minute ventilation (VE) and between VO2 and tidal volume in the physical load test, but no correlations were observed in the noxious audio stimulation test. There was a volume-based increase in respiratory patterns in physical load; however, VE increased not only for the adjustment of metabolic needs but also for individual mental factors; anxiety participated in this increase. In the high-anxiety group, the VE-to-VO2 ratio, indicating ventilatory efficiency, increased in both tests. In the high-anxiety group, increases in respiratory rate contributed to a VE increase, and there were negative correlations between expiratory time and anxiety scores in both tests. In an awake state, the higher neural structure may dominantly affect the mechanism of respiratory rhythm generation. We focus on the relationship between expiratory time and anxiety and show diagrams of respiratory output, allowing for individual personality.

Acoustic Stimulation↗

PubMed1998

Central histaminergic neurons regulate rabbit tracheal tension through the cervical sympathetic nerve.

We previously showed that stimulation of the posterior hypothalamus decreases tracheal tension and involves central histaminergic neurons. In the present study, we reveal that central histaminergic neurons project to the rostral ventrolateral medulla and affect cervical sympathetic nervous activity in rabbits. Administration of histamine into the fourth ventricle increased cervical sympathetic nervous activity and decreased tracheal tension. These effects were inhibited by administration of a histamine H receptor antagonist, pyrilamine, into the fourth ventricle. Unilateral injection of DL-homocysteic acid into the tuberomammillary nucleus increased cervical sympathetic nervous activity, an effect was antagonized by bilateral injection of pyrilamine into the rostral ventrolateral medulla. The pulse correlogram between the stimulation pulse applied to the tuberomammillary nucleus and the cervical sympathetic nerve activity showed a mode at 150 to 200 ms, which was reduced by pyrilamine administration into the fourth ventricle. Fibers anterogradely labeled by Phaseolus vulgaris leucoagglutinin (PHA-L) injected into the tuberomammillary nucleus were distributed in the A1, A2, C1, and C2 areas which are determined by tyrosine hydroxylase-immunohistochemistry. PHA-L positive neurons were in close contact with tyrosine hydroxylase-immunoreactive neurons in these four areas. Cell bodies in the tuberomammillary nucleus retrogradely labeled with fluorogold from the rostral ventrolateral medulla were immunoreactive with histamine. These results suggest that an excitatory efferent pathway projects from the tuberomammillary nucleus to the cervical sympathetic nerve and that the histaminergic neurons of this pathway influence tracheal tension through the rostral ventrolateral medulla.

Animals↗

PubMed1998

Vasopressin neuron activation and Fos expression by stimulation of the caudal ventrolateral medulla.

The present study demonstrates that projections ascending from the caudal ventrolateral medulla have direct effects on the expression of the immediate early gene c-fos and of the arginine-vasopressin gene in neurosecretory cells of the hypothalamic supraoptic nucleus. Intense Fos-like immunoreactivity (Fos-LI) was observed in many magnocellular neurons of the supraoptic nucleus after electrical stimulation of the caudal ventrolateral medulla. In sham-operated rats, Fos-LI was absent or present in very few magnocellular neurons in the supraoptic nucleus. Fos-LI was visible in neurons expressing arginine-vasopressin, and was seen rarely in oxytocin neurons by double-immunostaining method. This study showed that 76% of all Fos-positive cells were arginine-vasopressin immunoreactive, whereas only 4% of them showed oxytocin immunoreactivity in the supraoptic nucleus. With in situ hybridization, a high level of arginine-vasopressin mRNA was noted in the supraoptic nucleus 3 h after stimulation of the caudal ventrolateral medulla; the expression was highest 6 h after the stimulation compared with the same region in sham-operated animals. These findings suggest that noradrenaline, released from the axon terminals originating from the caudal ventrolateral medulla, may participate in the regulation of gene transcription of arginine-vasopressin in response to physiological stimuli.

Afferent Pathways↗

PubMed1998

Possible synaptic connections of expiratory neurons in the medulla of newborn rat in vitro.

To elucidate synaptic interactions between expiratory (Exp) and other respiratory neurons in the ventrolateral medulla of brain stem-spinal cord preparations from newborn rats, we analyzed postsynaptic potentials in Exp and a subclass of inspiratory (Insp) neurons using whole-cell recordings. About 72% of the Exp neurons (Exp-p-i) showed Cl--dependent synaptic inhibition during the Insp and pre/post-Insp phases, corresponding to the active phase of the Insp and pre-inspiratory (Pre-I) neurons, respectively. The other 28% neurons (Exp-i) received Cl--dependent inhibition during the Insp phase only. Some Insp neurons showed reversed IPSPs during the active phase of Exp-p-i after Cl-loading. We suggest the existence of inhibitory connections from Pre-I and Insp to Exp and from Exp to Insp neurons. Basic synaptic connections among respiratory neurons similar to those in intact adult mammals may already exist in newborn rats.

Animals↗

PubMed1998

The adrenergic modulation of firings of respiratory rhythm-generating neurons in medulla-spinal cord preparation from newborn rat.

We analysed the modulation of respiratory neurons by adrenaline or noradrenaline (NA) in a newborn rat brainstem-spinal cord preparation. Adrenaline or NA caused a dose-dependent depression of the respiratory rhythm and induced C4 spinal tonic discharges. The inhibitory effect of adrenaline (ED50=0.5 microM) on the respiratory rhythm was stronger than NA (ED50=5 microM). The adrenaline respiratory rhythm depression was partially blocked by the alpha1-antagonist prazosin or by the alpha2-antagonist yohimbine. The C4 tonic discharge elicited by adrenaline was blocked by the alpha1-antagonist prazosin. The direct effects of adrenaline on pre-inspiratory (Pre-I) neurons were examined in a synaptic blockade solution (low Ca), and fifty-six percent of Pre-I neurons were found to continue firing. In low-Ca solution, Pre-I neurons were excited (n=29 of 39) or depressed (n=5 of 39) by adrenaline, and excited by alpha1-agonist phenylephrine or depressed by alpha2-agonist clonidine. These results suggest that the respiratory rhythm depression under intact network conditions is mediated by some other inhibitory system. The inhibitory effect of adrenaline on the respiratory rhythm was partially blocked by the GABA(A)-antagonists bicuculline or picrotoxin, but not by the GABA(B)-antagonist phaclofen. The present results suggest that: (1) respiratory rhythm generation is more sensitive to adrenaline than NA through alpha-adrenergic action of adrenaline; (2) the activity of Pre-I neurons could be directly regulated by excitation via alpha1-receptors and inhibition via alpha2-receptors; and (3) the depression of the respiratory rhythm by adrenaline is partly mediated by GABA(A)ergic neurons.

Adrenergic alpha-Agonists↗

PubMed1998

Modulation of respiratory rhythm by 5-HT in the brainstem-spinal cord preparation from newborn rat.

Effects of 5-hydroxytryptamine (5-HT) on inspiration-related nerve activity and membrane potential of respiratory neurons in the ventrolateral medulla were studied in brainstem-spinal cord preparations isolated from newborn rats. Bath application of 5-100 microM 5-HT induced a biphasic response in inspiratory nerve activity: a transient increase in respiratory frequency followed by a decrease in the rate of discharge. The excitatory effect of 5-HT was particularly prominent in preparations with a respiratory rate of less than 3 min-1, whereas the inhibitory effect was more pronounced in preparations with a higher respiratory rate. In pre-inspiratory (Pre-I) and inspiratory (Insp) neurons, 20 microM 5-HT induced a membrane depolarization of up to 10 mV accompanied by a significant decrease in the input resistance. Membrane depolarization by 5-HT was also evident in the presence of tetrodotoxin. In Pre-I neurons, 5-HT caused an increase in the burst rate, which was followed by a decrease in the intraburst firing frequency and burst amplitude, although the burst rate remained high. The burst rate in Insp neurons first increased and subsequently decreased without significant change in the intraburst firing frequency. Simultaneous intra- and extracellular recordings (in the contralateral medulla) of Pre-I/Pre-I neuron or Pre-I/Insp neuron pairs revealed that 5-HT disturbed the correlation between these neuron bursts. Increase in the respiratory rate induced by 20 microM 5-HT was completely blocked by pretreatment (5-15 min) with 5 microM ketanserin or 1 microM methysergide, but not by 10 microM propranolol. None of these antagonists blocked the inhibitory effects of 5-HT. A 5-HT2 agonist, 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 10-100 microM) increased the respiratory rate. Perfusion with a 5-HT1A agonist, 8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT, 20-100 microM) induced an increase or a decrease in the respiratory rate. A 5-HT2C agonist, 1-(3-chlorophenyl)piperazine (m-CPP, 2-10 microM) induced an initial decrease in the respiratory rate followed by a further long- lasting decrease. Burst activity of Pre-I neurons was suppressed upon administration of 10 microM m-CPP and enhanced with 20 microM DOI. The results suggest that changes in the bursting properties of Pre-I and Insp neurons induced by 5-HT lead to modulation of the respiratory network, thus causing biphasic modulation of the respiratory rhythm. In addition to effects via 5-HT1A receptors, activation of 5-HT2A and 5-HT2C receptor subtypes might be involved in excitatory effects and inhibitory effects of 5-HT respectively.

Animals↗

PubMed1998

Autoregulation of histamine release in medulla oblongata via H3-receptors in rabbits.

The release of histamine (HA) from the rostral ventrolateral medulla (RVL), the raphe nuclei (nR), and the solitary nucleus (nTS) was investigated in anesthetized rabbits using microdialysis and high-performance liquid chromatography. HA release upon electrical stimulation of the posterior hypothalamus (PH), where histaminergic cell bodies are located, was increased to 168% of the baseline level in the RVL (n = 6), 139% of the baseline level in the nR (n = 5), and 166% of the baseline level in the nTS (n = 4). Upon perfusion of thioperamide, an H3-receptor antagonist, via a microdialysis probe, HA release from the RVL, nR and nTS increased. The increase in HA release from the RVL, nR and nTS following thioperamide perfusion was suppressed by co-perfusion of thioperamide and an H3-receptor agonist, imetit. We found that HA is released from the RVL, nR and nTS, that the HA release from all three areas is increased upon stimulation of the PH, and that the HA release is locally influenced in opposite directions by thioperamide and imetit. These results suggest that HA release in the medulla oblongata is controlled by the PH and that H3-receptors participate in the autoregulation of HA release by providing negative feedback locally. Autoregulation of HA release via H3-receptors may be important for maintaining tonic output to the sympathetic nervous system.

Animals↗