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Biomedical subjects

Y Koyama

Publications and source records attributed to Y Koyama.

At least 91 records · Page 5Linked to original sources
PubMed2000

Modulation of presumed cholinergic mesopontine tegmental neurons by acetylcholine and monoamines applied iontophoretically in unanesthetized cats.

The mesopontine tegmentum, which contains both cholinergic and non-cholinergic neurons, plays a crucial role in behavioral state control. Using microiontophoresis in unanesthetized cats, we have examined the effect of cholinergic and monoaminergic drugs on two putative cholinergic neurons located mostly in the laterodorsal tegmental nucleus and X area (or the cholinergic part of the nucleus tegmenti pedunculopontinus, pars compacta): one (type I-S) exhibiting slow tonic discharge during both waking and paradoxical sleep, and the other (PGO-on) displaying single spike activity during waking and burst discharges in association with ponto-geniculo-occipital (PGO) waves during paradoxical sleep. We found that: (i) application of carbachol, a potent cholinergic agonist, inhibited single spike activity in both PGO-on and type I-S neurons, but had no effect on the burst activity of PGO-on neurons during paradoxical sleep; the inhibition was associated with either blockade or increased latency of antidromic responses, suggesting membrane hyperpolarization; (ii) application of glutamate, norepinephrine, epinephrine, or histamine resulted in increased tonic discharge in both PGO-on and type I-S neurons; this was state-independent and resulted in a change in the firing mode of PGO-on neurons from phasic to tonic; (iii) application of serotonin had only a weak state-dependent inhibitory effect on a few type I-S neurons; and (iv) application of dopamine had no effect on either type of neuron. The present findings suggest that cholinergic, glutamatergic and monoaminergic (especially noradrenergic, adrenergic and histaminergic) inputs have the capacity to strongly modulate the cholinergic neurons, altering both their rate and mode of discharge, such as to shape their state specific activity, and thereby contribute greatly to their role in behavioral state control.

Acetylcholine↗
PubMed2000

Endothelins increase tyrosine phosphorylation of astrocytic focal adhesion kinase and paxillin accompanied by their association with cytoskeletal components.

Astrocytic endothelin receptors are involved in the appearance of activated astrocytes upon injury of the brain [Ishikawa N. et al. (1997) Eur. J. Neurosci. 9, 895-901; Koyama Y. et al. (1999) Glia 26, 268-271]. To clarify signal transduction triggered by endothelin receptors, we examined the effects of endothelins on protein tyrosine phosphorylation in cultured rat astrocytes. Endothelin-1 (1 nM) increased tyrosine phosphorylation of focal adhesion kinase and paxillin. The tyrosine phosphorylation was also induced by endothelin-1 (1 nM) and Ala(1,3,11,15)-endothelin-1 (10nM), an endothelin-B receptor agonist. BQ788 (100 nM), an endothelin-B receptor antagonist, inhibited the effects of endothelin-3. Orthovanadate (VO(4)(3-)), a tyrosine phosphatase inhibitor, but not bradykinin (1 microM), angiotensin II (100 nM), A23187 (5 microM) and phorbol 12-myristate 13-acetate (100 nM), increased tyrosine phosphorylation of focal adhesion kinase and paxillin. The tyrosine phosphorylation by endothelin-3 was not prevented by pertussis toxin, Ca(2+) chelation, protein kinase C inhibitors (calphostin C and staurosporine) or wortmannin. Immunocytochemical staining showed that endothelin-3 and VO(4)(3-) induced redistribution of focal adhesion kinase and paxillin to focal adhesions concomitant with stress fiber formation in dibutyryl cyclic-AMP-treated astrocytes. Treatment with endothelin-3 and VO(4)(3-) increased focal adhesion kinase and paxillin associated with astrocytic cytoskeletal fraction. In the presence of cytochalasin B, an actin disrupting agent, endothelin-3 and VO(4)(3-) did not phosphorylate focal adhesion kinase and paxillin. Application of cytochalasin B after treatment with endothelin-3 and VO(4)(3-) stimulated dephosphorylation of focal adhesion kinase and paxillin. These results suggest that the associations of focal adhesion kinase and paxillin with cytoskeletal components are required in the endothelin-induced tyrosine phosphorylation of the astrocytic proteins.

Androstadienes↗
PubMed2000

Effect of antagonistic voluntary contraction on motor responses in the forearm.

OBJECTIVE: We investigated the effects of voluntary contraction of agonist and antagonist muscles on motor evoked potentials (MEP) and on myoelectric activities in the target (agonist) muscle following transcranial magnetic stimulation (TMS). METHODS: The left extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles were studied in 16 healthy subjects. H reflexes, MEP induced by TMS, and background electromyographic (EMG) activity were recorded using surface electrodes at rest and during voluntary contraction of either agonist or antagonist muscles. RESULTS: Voluntary contraction of antagonist muscles (at 10% of maximum contraction) enhanced the amplitudes of MEP for both muscles. The H reflex of the FCR muscle was inhibited by contraction (10% of maximum) of the ECR muscle. Background EMG activity did not differ between H-reflex trials and TMS trials. Enhancement of MEP amplitudes and background EMG activity during voluntary antagonist contraction was comparable in the two muscles. Appearance rate of MEP recorded by needle electrodes in response to subthreshold TMS was increased by antagonistic voluntary contraction. CONCLUSION: Facilitation occurs during voluntary contraction of antagonist muscles. Differences between the effects of voluntary contraction of the ECR muscle for the MEP and the H reflex of the FCR suggest that cortical facilitatory spread occurs between agonist and antagonist muscles.

Adult↗
PubMed2000

Transactivation of EGF receptor induced by angiotensin II regulates fibronectin and TGF-beta gene expression via transcriptional and post-transcriptional mechanisms.

The signaling cascade elicited by angiotensin II (Ang II) resembles that characteristic of growth factor, and recent evidence indicates transactivation of epidermal growth factor receptor (EGF-R) by G protein-coupled receptors. Here, we report the involvement of EGF-R in Ang II-induced synthesis of fibronectin and TGF-beta in cardiac fibroblasts. Ang II stimulated fibronectin mRNA levels dose-dependently with a maximal increase (approximately 5-fold) observed after 12 h of incubation. Ang II-, or calcium ionophore-induced fibronectin synthesis was completely abolished by tyrosine kinase inhibitors and intracellular Ca2+ chelating agents. Ang II-induced fibronectin mRNA was not affected by PKC inhibitors or PKC depletion, whereas specific inhibition of EGF-R function by a dominant negative EGF-R mutant and tyrphostin AG1478 abolished induction of fibronectin mRNA. We isolated the rat fibronectin gene including the 5'-flanking region and found that the AP-1 binding site present in the promoter region was responsible for the Ang II responsiveness of this gene. Gel retardation assay revealed the binding of nuclear protein to the AP-1 site, which was supershifted with anti-c-fos and anti-c-jun but not anti-ATF-2 antibodies. Conditioned medium from Ang II-treated cells contained TGF-beta bioactivity and addition of neutralizing TGF-beta antibody modestly (46%) inhibited induction of fibronectin. Ang II-induced synthesis of TGF-beta was also abolished by inhibition of EGF-R function. The effect of TGF-beta was exerted by stabilizing fibronectin mRNA without affecting the promoter activity and required de novo protein synthesis. We concluded that Ang II-induced expression of fibronectin and TGF-beta is mediated by downstream signaling of EGF-R transactivated by Ca2+-dependent tyrosine kinase, and that Ang II-induced fibronectin mRNA expression is regulated by two different mechanisms; transcriptional control by binding of c-fos/c-jun complex to the AP-1 site, and post-transcriptional control by mRNA stabilization due to autocrine and/or paracrine effects of TGF-beta. Thus, this study suggested that the action of Ang II on extracellular matrix formation should be interpreted in association with the EGF-R signaling cascade.

Angiotensin II↗
PubMed2000

The Na+-Ca2+ exchange inhibitor KB-R7943 inhibits high K+-induced increases in intracellular Ca2+ concentration and [3H]noradrenaline release in the human neuroblastoma SH-SY5Y.

The effects of the Na+-Ca2+ exchange inhibitor 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate (KB-R7943) on depolarization-induced Ca2+ signal and [3H]noradrenaline release were examined in SH-SY5Y cells. KB-R7943 at 10 microM significantly inhibited high K+-induced increase in intracellular Ca2+ concentration. KB-R7943 also inhibited high K+-evoked release of [3H]noradrenaline from the cells. These findings suggest that the Na+-Ca2+ exchanger in the reverse mode is involved at least partly in depolarization-induced transmitter release.

Calcium↗
PubMed2000

Efficient light harvesting through carotenoids.

We review the factors that control the efficiency of carotenoid-chlorophyll excitation transfer in photosynthetic light harvesting. For this we summarize first the recently developed theory that describes electronic couplings between carotenoids and chlorophylls and we outline in particular the influence of length of conjugated system and of symmetry breaking on the couplings. We focus hereby on the structurally solved lycopene-BChl system of LH 2 from Rhodospirillum molischianum and the peridinin-Chl a system of PCP from Amphidinium carterae. In addition, we review recent spectroscopic data for neurosporene, spheroidene and lycopene, three carotenoids with different lengths of conjugated systems. On the basis of the measured energies, emission lineshapes, solution and protein environment lifetimes for their 2A ( g ) (-) and 1B ( u ) (+) states as well as of the theoretically determined couplings, we conclude that the transfer efficiencies from the 2A ( g ) (-) state are controlled by the Car(2A ( g ) (-) )-BChl(Q(g)) electronic couplings and the 2A ( g ) (-) --> 1A ( g ) (-) internal conversion rates. We suggest that symmetry breaking and geometry rather than length of conjugated system dominate couplings involving the 2A ( g ) (-) state. Differences in transfer efficiencies from the 1B ( u ) (+) state in LH 2 and PCP are found to be dominated by the differences in spectral overlap. The role of the 1B ( u ) (+) state is likely to be influenced by a lower-lying (in longer polyenes), optically forbidden 1B ( u ) (-) state.

Journal Article↗
PubMed2000

Postsynaptic 5-hydroxytryptamine(1A) receptor activation increases in vivo dopamine release in rat prefrontal cortex.

5-Hydroxytryptamine (5-HT) plays a role in the regulation of 3, 4-dihydroxyphenylethylamine (dopamine) neurons in the brain, but the precise mechanism of regulation by 5-HT(1A) receptors of dopamine release has not been defined. The present study describes the effect of 5-¿3-[[(2S)-1,4-benzodioxan-2ylmethyl]amino]propoxy¿-1, 3-benzodioxole HCl (MKC-242), a highly potent and selective 5-HT(1A) receptor agonist, on dopamine release in the prefrontal cortex using microdialysis in the freely moving rat. Subcutaneous injection of MKC-242 (0.3 - 1.0 mg kg(-1)) increased extracellular levels of dopamine in the prefrontal cortex. The effect of MKC-242 in the prefrontal cortex was antagonized by pretreatment with the selective 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohe xanecarboxamide (WAY100635; 1 mg kg(-1), i.p.). Local application of WAY100635 (10 microM) via a microdialysis probe antagonized the effect of systemic MKC-242 in an increasing dopamine release, and locally infused 8-hydroxy-2-(di-n-propylamino)tetralin (10 microM) increased dopamine release in the prefrontal cortex. MKC-242 increased cortical dopamine release in the rats pretreated with 5, 7-dihydroxytryptamine (150 microgram, i.c.v.) that caused an almost complete reduction in cortical 5-HT content. The effect of MKC-242 to increase dopamine release was also observed in the hippocampus, but not in the striatum or nucleus accumbens. Fluoxetine, a selective serotonin reuptake inhibitor, increased dopamine release in the prefrontal cortex, but not in the nucleus accumbens, while buspirone, a 5-HT(1A) receptor agonist, increased dopamine release in both brain regions. The present results indicate that activation of postsynaptic 5-HT(1A) receptors increases dopamine release in a brain region-specific manner.

5,7-Dihydroxytryptamine↗
PubMed2000

Suspected intestinal myiasis due to Dryomyza formosa in a Japanese schizophrenic patient with symptoms of delusional parasitosis.

A third-stage larva of Dryomyza formosa (Wiedemann) (Diptera: Dryomyzidae) was found in the fresh stool of a 27-year-old Japanese woman resident of Shiobara, 150 km north of Tokyo, on 16 November 1998. This is the first record of myiasis due to Dryomyza. Detection of this maggot (2cm long) by the patient herself was associated with her longstanding delusion of abdominal parasitosis as a symptom of chronic schizophrenia. Circumstantial evidence agreed with this being a genuine case of intestinal myiasis, apparently due to accidental ingestion of the insect, with no signs that the patient had contrived the report, nor that the maggot had invaded the stool post-defaecation. This case draws attention to the likelihood that some personality states are predisposed to noticing and reporting myiasis, when it occurs. We review other conditions (mental and physical) that are more prone to myiasis.

Adult↗
PubMed2000

The effects of prolactin on the mesopontine tegmental neurons.

In urethane-anaesthetized rats, single neuronal activity was recorded extracellularily in and around the laterodorsal tegmental nucleus, and the response to prolactin applied by pressure injection was examined. Three of six cholinergic neurons tested were excited by prolactin for more than 1 min. In two of three non-cholinergic neurons tested, prolactin application caused excitation which lasted a shorter time than that in the cholinergic neurons. The results suggest that prolactin may have physiological influences on these mesopontine neurons to increase paradoxical sleep.

Animals↗
PubMed2000

Are micturition systems influenced by sleep-arousal system?

To clarify a relation between contractile condition of the urinary bladder and vigilance condition, bladder pressure was monitored simultaneously with cortical electroencephalogram (EEG) in urethane-anesthetized rats. Slow waves of large amplitude and those of lower amplitude appeared in EEG alternately. The bladder showed no contractile activity in the former EEG condition, while it contracted intermittently or continuously to urinate in the latter EEG condition. The relative power of EEG delta waves was significantly different in these two conditions. These results suggest that activity of the micturition system changes according to vigilance conditions, which may serve to prevent enuresis during sleep.

Animals↗
PubMed2000

Pelvic congestion syndrome caused by inferior vena cava reflux.

We present a female patient who had pelvic congestion syndrome caused by inferior vena cava reflux associated with tricuspid regurgitation, but without other symptoms or signs related to her tricuspid regurgitation. Bladder pumping therapy was effective in improving her symptoms.

Female↗
PubMed2000

Impact of citrate therapy on the circadian rhythm of urinary magnesium ammonium phosphate saturation in normal individuals.

BACKGROUND: Alkaline citrate has been used widely in the prevention of stone formation. However, the risk of struvite stone during the alkalinizing therapy has not been adequately studied in terms of magnesium ammonium phosphate saturation. METHODS: The circadian rhythm of the urinary saturation of magnesium ammonium phosphate was estimated by using the differential Gibbs' free energy values of magnesium ammonium phosphate before and during 5 days of treatment with sodium-potassium citrate (1 g t.i.d., 1 g q.i.d. or 3 g t.i.d.) in five healthy male volunteers. RESULTS: The magnesium ammonium phosphate saturation varied during the day, peaking far below the solubility product between 08.00 and 10.30 h and between 13.00 and 18.00 h. The mean peak levels were increased by each treatment regimen in comparison with the control day. The mean increase on day 1 was significant between 10.30 and 23.00 h with the 3 g t.i.d. regimen, but the mean saturation still remained below the solubility product throughout the day. CONCLUSIONS: The urinary magnesium ammonium phosphate saturation appeared hard to exceed the solubility product with a high dose of alkaline citrate.

Adult↗
PubMed2000

Mice with markedly reduced PACAP (PAC(1)) receptor expression by targeted deletion of the signal peptide.

In an attempt to study the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 (PAC(1)) receptor (PAC(1)R) function in vivo and to produce a mouse model with altered expression of PAC(1)R, we have used gene targeting in embryonic stem cells to disrupt exon 2 of the PAC(1)R gene, which contains the ATG translation start site and the signal peptide. Un-expectedly, active transcription of PAC(1)R mRNA was detected in the mutant mice; however, exon 1 was spliced to exon 3 (skipping exon 2), and (125)I-PACAP27 binding in brain was greatly reduced. PAC(1)R exon 2(-/-) mice were viable, fertile, and morphologically and histologically indistinguishable from their wild-type counterparts. We next examined the ligand binding and cell surface expression of the mutant receptor lacking the signal peptide in transfected COS-7 cells. (125)I-PACAP27 binding of the mutant receptor was approximately one-tenth of that in the wild-type receptor. Although the wild-type receptor was expressed abundantly in both the plasma membrane and the cytoplasm around the nucleus, the mutant receptor was expressed in the plasma membrane with a markedly reduced level. Digestion of the membranes with endoglycosidase F greatly reduced the size of the wild-type receptor but only slightly reduced that of the mutant receptor. These results demonstrate that the signal peptide is required for efficient cell surface expression and N-linked glycosylation of the PAC(1)R. However, the mutant receptors still functionally coupled to adenylate cyclase in COS-7 cells, suggesting the presence of sufficient spare receptors such that the mutant receptors are capable of activating the second messenger system. We suggest that the mutant mice with markedly reduced PAC(1)R expression can serve as a useful animal model or cell culture system for further studies in PAC(1)R function.

Animals↗
PubMed2000

Synergistic induction of pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression by nerve growth factor and PACAP in PC12 cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression was analyzed in PC12 cells. PC12 cells transfected with a PACAP promoter-luciferase reporter construct were utilized to investigate the effects of PACAP, either alone or in combination with nerve growth factor (NGF), on PACAP transcriptional response. PACAP induced transcription from the PACAP promoter through PACAP type I receptor (PAC1 receptor). PACAP gene transcription was also induced by NGF. Simultaneous treatment with PACAP and NGF resulted in a synergistic transcriptional response that was more than three times the predicted response, based on a simple additive effect of both agents. This synergism in transcriptional response paralleled the PACAP mRNA levels, as determined by RT-PCR and northern blotting. The level of PACAP mRNA peaked 3 h after stimulation and gradually returned to basal levels by 48 h. PC12 cells are known to express predominantly the hop isoform of the PAC1 receptor, which positively couples to both adenylate cyclase and phospholipase C. To determine the role of the cyclic AMP and protein kinase C pathways in PACAP gene expression, the effects of forskolin and phorbol 12-myristate 13-acetate (PMA) were then examined. PMA did not alter PACAP mRNA levels but enhanced forskolin-induced PACAP mRNA expression. Down-regulation of protein kinase C blocked the ability of PACAP to stimulate PACAP mRNA expression. The mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) kinase 1/2 (MEK1/2) inhibitor PD98059 also blocked the PACAP mRNA expression induced by either PACAP or NGF but not that induced by a combination of PACAP and NGF. These results suggest that PACAP stimulates the PACAP gene expression in PC12 cells at least in part through activation of adenylate cyclase and protein kinase C signaling pathways and that the ERK1/2 cascade is involved in PACAP and NGF-induced PACAP gene expression, although redundant signaling pathways may also be involved. The present finding showing that PACAP in combination with NGF causes a synergistic increase in PACAP gene expression in PC12 cells supports the idea that PACAP acts as an autocrine regulatory factor.

Animals↗
PubMed2000

Isolation and purification of the reaction center (RC) and the core (RC-LH1) complex from Rhodobium marinum: the LH1 ring of the detergent-solubilized core complex contains 32 bacteriochlorophylls.

The reaction center (RC) and the core (RC-LH1) complex were isolated and purified from Rhodobium marinum; together with the LH1 complex [Meckenstock et al. (1992a) FEBS Lett. 311: 128], a complete set of RC, LH1 and RC-LH1 from the same wild-type strain of a purple photosynthetic bacterium can therefore now be made. Comparison of the BChl a/BPhe a ratio (determined by HPLC) between the RC and the RC-LH1 complexes lead us to the determination of the number of BChls in the LH1 ring to be 32.06+/-2.90, indicating that the LH1 ring from Rh. marinum consists of 16 alphabeta subunits.

Bacteria↗
PubMed2000

Line versus representational bisections in unilateral spatial neglect.

OBJECTIVES: To clarify the mechanisms of left unilateral spatial neglect found in the bisection of lines after cueing to the left end point and to determine whether neglect occurs for the mental representation of a line. METHODS: A new representational bisection task was developed to eliminate the influence of the right segment of the physical line that would attract attention. Eight patients with typical left unilateral spatial neglect underwent line and representational bisection tasks on a computer display with a touch panel. In the line bisection with cueing, they bisected a line after touching the left end point. In the representational bisection, the patients were presented with a line until they touched the left end point. On the blank display, they pointed to the subjective midpoint of the erased line. The performances of the two bisection tasks were compared when the length and position of stimulus lines were varied. RESULTS: The rightward errors in the representational bisection were greater than or equivalent to those in the line bisection with cueing. The effect of line length in which the errors became greater for the longer lines was equally found in the line bisection with cueing and the representational bisection. This was confirmed in the condition where the right end point was placed at a fixed position and the line length was varied. CONCLUSIONS: After cueing to the left end point, rightward bisection errors of patients with neglect are not caused by overattention to the right segment of the physical line. Left neglect occurs mainly for the mental representation formed at the time of cueing or seeing the whole extent of a line.

Aged↗
PubMed2000

Effects of 'cool-down' during exercise recovery on cardiopulmonary systems in patients with coronary artery disease.

The effects of 'cool-down' during exercise recovery on cardiovascular and respiratory systems have not been fully clarified. The recovery of respiratory gasses was compared in cardiac patients after maximal exercise during which subjects either performed a cool-down or rested. Twenty-one patients (61+/-10 years) with coronary artery disease performed 2 symptom-limited incremental exercise tests on a cycle ergometer: one with a cool-down and the other without during recovery from the maximal exercise test. Expired gasses were analyzed on a breath-by-breath basis throughout the test and for 6min of recovery. Without a cool-down, the ventilatory equivalent for O2 (VE/O2) increased dramatically during recovery compared with the resting values or those of peak exercise: 44.5+/-7.7 at rest, 44.0+/-10.6 at peak exercise and 63.3+/-14.5 after 2min of recovery. End-tidal PO2 (P(ET)O2) also increased significantly during recovery. However, the overshoot phenomenon of these variables was attenuated when cool-down exercise was performed during recovery. The high ratio of VE/VO2 reflects ventilation perfusion (VA/Q) unevenness and P(ET)O2 is an index of arterial PO2. Thus, it is suggested that cool-down exercise during recovery after maximal exercise testing provides beneficial effects on the respiratory system by decreasing the VA/Q unevenness and relative hyperventilation that are observed when cool-down exercise is not performed.

Adult↗