PubMed Health⌕ Search

Biomedical subjects

E Miyamoto

Publications and source records attributed to E Miyamoto.

At least 19 recordsLinked to original sources
PubMed2006

Changes in Ca(2+)/calmodulin-dependent protein kinase II activity and its relation to performance in passive avoidance response and long-term potentiation formation in mice prenatally exposed to diethylstilbestrol.

We investigated the effects of prenatal exposure to diethylstilbestrol (DES), an endocrine disrupter on learning behavior and synaptic functions. Specifically, we determined the activity of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and related kinases that play an essential role in long-term potentiation (LTP) in the hippocampus in mice that were prenatally exposed to DES. Treatment with DES resulted in increased CaMKII autophosphorylation and Ca(2+)-independent activity in the hippocampus and cortex of male mice. Impaired passive avoidance correlated with this increased CaMKII autophosphorylation, as did the enhanced early phase of LTP (E-LTP) in hippocampus. These data suggest that prenatal exposure to DES induces deficits in passive avoidance responses as a result of increased CaMKII activity and hippocampal LTP.

Animals↗
PubMed2003

Inhibitory effect of propofol on ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices is mediated by GABAA receptor activation.

BACKGROUND: Non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, including ketamine, have psychotomimetic activities and cause neuronal damage in the posterior cingulate and retrosplenial cortices (PC/RS), which are suggested to be the brain regions responsible for their psychotomimetic activities. We previously demonstrated that ketamine induced marked c-Fos (c-fos protein) expression in the rat PC/RS, which was inhibited by propofol, and the expression was closely related to ketamine-induced abnormal behavior. In the present study, we investigated whether the inhibition by propofol was mediated by GABAA receptor receptor activation. METHODS: Using Wistar rats, propofol alone, propofol with bicuculline or propofol with flumazenil was injected intravenously and then continuously infused. Fifteen minutes later, 100 mg kg-1 of ketamine or normal saline was injected intraperitoneally. Two hours after the ketamine or saline injection, the brain was extracted and brain sections were prepared, and c-Fos expression was detected using immunohistochemical methods. RESULTS: Ketamine induced marked c-Fos expression in the PC/RS (171 +/- 9/0.4 mm2), which was significantly inhibited by propofol (5 +/- 5/0.4 mm2). The inhibition by propofol was disinhibited dose-dependently by both bicuculline (0.5 and 1.0 mg kg-1 bicuculline groups: 46 +/- 15 and 143 +/- 16, respectively) and flumazenil (0.1 and 1.0 mg kg-1 flumazenil groups: 79 +/- 6 and 130 +/- 15, respectively). CONCLUSION: These results demonstrate that the inhibitory effect of propofol on ketamine-induced c-Fos expression in the PC/RS is mediated by GABAA receptor activation, and suggests that ketamine-induced psychoneuronal adverse effects may be suppressed by propofol via the activation of GABAA receptors.

Anesthetics, Dissociative↗
PubMed2002

A case of paraneoplastic syndrome accompanied by two types of cancer.

A case of paraneoplastic syndrome accompanied by two types of cancer is reported. The patient was a 62 year old man who progressively developed cerebellar ataxia, especially an abnormal gait. The anti-Hu antibody titre was high. A small tumour was detected in the middle lobe of the right lung and was surgically treated. The histology was adenocarcinoma. After lobectomy, however, the ataxia deteriorated, and plasma exchange, 250 ml/kg/day, was conducted for 6 days. After plasma exchange, the anti-Hu antibody titre decreased and the ataxia temporarily ceased to progress. A week after the last plasma exchange, a mass appeared in the anterior cervical region and rapidly increased in size. The biopsy of the neck tumour disclosed a small cell carcinoma. Five months later small cell carcinoma appeared in the left lung. This case shows the importance of searching for small cell carcinoma when anti-Hu antibodies are detected. It is assumed that plasma exchange removed not only a pathogenic factor of ataxia but also a factor which inhibited the growth of the small cell carcinoma. It is recommended that plasmapheresis should be performed with caution in paraneoplastic syndrome when the origin of a tumour is obscure.

Adenocarcinoma↗
PubMed2002

[Calcium signaling and brain functions].

Calcium signaling plays a critical role in various cell types by activation of receptors and Ca2+ channels in response to neurotransmitters, hormones, growth, factors etc. Although a variety of functions of intracellular Ca2+ are reported, Ca2+/calmodulin-dependent protein kinases (CaMK) are involved in their mediation. We have been studying on CaMK I, II, III, IV and K in the dynamic regulation in the cells in relation to functions. In this study, we elucidated the structures of the isoforms of CaMKII subunits with nuclear translocation signal (NTS). NTS is included in the variable domain following the regulatory domain with a sequence of KKRK. The isoforms of CaMK subunits such as alpha B, gamma A, gamma A.B, delta 3 and delta 7 contain NTS in the sequences of the structures. Transfection of the isoforms with NTS into NG108-15 cells stimulated the expression of brain-derived neurotrophic factor in the cytoplasm. Activation of CaMKII and IV and mitogen-activated protein kinase (MAPK) was observed during long-term potentiation (LTP) induction in the CA1 area of hippocampus. The activation of CaMKII was sustained for a long period, whereas that of CaMKIV and MAPK was transient. The results suggest that CaMKII is involved in LTP induction, while CaMKIV and MAPK are rather involved in LTP maintenance. We present and discuss our recent studies on regulation of CaMKs in neuronal functions.

Brain↗
PubMed2001

Caudoputamen is damaged by hypocapnia during mechanical ventilation in a rat model of chronic cerebral hypoperfusion.

BACKGROUND AND PURPOSE: Postoperative brain dysfunction, such as delirium, is a common complication of anesthesia and is sometimes prolonged, especially in patients with cerebrovascular disease. In the present study we investigated the effect of hypocapnia during anesthesia on neuronal damage using a rat model of chronic cerebral hypoperfusion. METHODS: Chronic cerebral hypoperfusion was induced by clipping the bilateral common carotid arteries in male Wistar rats. Fourteen days after the operation, these animals were mechanically ventilated for 2 hours and then kept in suitable conditions for an additional 14 days. Twenty-four rats were assigned to 4 groups: those with chronic cerebral hypoperfusion with either hypocapnia or normocapnia during anesthesia, and those given sham operation with either hypocapnia or normocapnia. White matter lesions in the brain sections were evaluated with Klüver-Barrera staining. Proliferation of glial cells was estimated with the use of immunohistochemistry of glial fibrillary acidic protein, a marker for astroglia, and CD11b, a marker for microglia. Computer-assisted morphometry was applied to the immunohistochemical results of microtubule-associated protein 2 to evaluate the loss of neurons. RESULTS: The histological damage was localized almost exclusively in the white matter in the rats subjected to chronic cerebral hypoperfusion but without hypocapnia. Neuronal damage and astroglial proliferation occurred with aggravated white matter lesions in the caudoputamen in the rats with chronic cerebral hypoperfusion and hypocapnia. No lesions were observed in sham-operated rats with either hypocapnia or normocapnia. CONCLUSIONS: These results indicate that hypocapnia during anesthesia causes tissue damage in the caudoputamen, which may be responsible for long-lasting postoperative delirium in patients with stroke and/or dementia.

Anesthesia↗
PubMed2001

An anxiolytic agent, dihydrohonokiol-B, inhibits ammonia-induced increases in the intracellular Cl(-) of cultured rat hippocampal neurons via GABA(c) receptors.

The effects of an anxiolytic honokiol derivative, dihydrohonokiol-B (DHH-B) [3'-(2-propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diaol], on ammonia-induced increases in the intracellular Cl(-) concentration ([Cl(-)](i)) were examined using primary cultured rat hippocampal neurons. DHH-B (1-100 ng/ml), but not an inactive isomer of honokiol, magnolol (100 ng/ml), dose-dependently inhibited the ammonia-induced increases in [Cl(-)](i) without any changes in the control [Cl(-)](i). Such an effect of DHH-B was blocked by a gamma-aminobutylic acid A (GABA(A)) and GABA(C) Cl(-) channel blocker, 100 microM picrotoxin, and a GABA(C) receptor blocker, 10 microM (1,2,5,6-tetrahydropyridine-4-yl)methylphosphinic acid, but not by a GABA(A) receptor blocker, 10 microM bicuculline. Further, a GABA(C) receptor agonist, 200 microM cis-4-aminocrotonic acid, but not a GABA(A) receptor agonist, 10 microM muscimol, mimicked the effect of DHH-B. Thus, DHH-B appears to protect neurons from the ammonia-induced increases in [Cl(-)](i) through GABA(C) receptor stimulation.

Ammonia↗
PubMed2001

Intravenously injected FK506 failed to inhibit hippocampal calcineurin.

FK506 (tacrolimus) is known as an inhibitor for calcineurin and is used in numerous research fields. It is not clear whether intravenously injected FK506 inhibits neuronal calcineurin. We measured the calcineurin activities of normal and postischemic rat hippocampi after intravenous injection of FK506 (3 mg/kg). Intravenously injected FK506 had no inhibitory effect on calcineurin activity in the hippocampi of normal and postischemic rats, whereas FK506 inhibited the calcineurin in vitro (purified enzyme, hippocampal homogenate, and hippocampal slice culture homogenate). Thus, it is considered that intravenously injected FK506 does not act on intraneuronal calcineurin and that several effects of FK506 are not due to the inhibition of neuronal calcineurin.

Animals↗
PubMed2001

Microglial signaling by amyloid beta protein through mitogen-activated protein kinase mediating phosphorylation of MARCKS.

Myristoylated alanine-rich C kinase substrate (MARCKS), an acidic protein associated with cell motility and phagocytosis, is activated upon phosphorylation by protein kinase C (PKC) and proline-directed protein kinases. In Alzheimer disease (AD), activated microglia expressing MARCKS migrates around senile plaques. We reported that amyloid beta protein (A beta), a major component of senile plaques, activated MARCKS through a tyrosine kinase and PKC-delta. We have now identified another A beta signaling pathway through a mitogen-activated protein kinase (MAPK) involved in the phosphorylation of MARCKS and analysed cross-talk between PKC and MAPK pathways in primary cultured rat microglia. A selective inhibitor for MAPK kinase, PD098059, significantly inhibited the phosphorylation of MARCKS induced by A beta. Extracellulary regulated kinases, the activities of which were induced by A beta, directly phosphorylated a recombinant MARCKS in vitro. The MAPK pathway was sensitive to wortmannin, but not to a PKC inhibitor or to tyrosine kinase inhibitors. The activation of PKC by A beta was not sensitive to wortmannin. Our findings suggest involvement of the MAPK pathway through phosphoinositol 3-kinase in the phosphorylation of MARCKS in rat cultured microglia, an event may be associated with mechanisms activating microglia in AD.

Amyloid beta-Peptides↗
PubMed2001

Activation of calcium/calmodulin-dependent protein kinase IV in long term potentiation in the rat hippocampal CA1 region.

The importance of well characterized calcium/calmodulin-dependent protein kinase (CaMK) II in hippocampal long term potentiation (LTP) is widely well established; however, several CaMKs other than CaMKII are not yet clearly characterized and understood. Here we report the activation of CaMKIV, which is phosphorylated by CaMK kinase and localized predominantly in neuronal nuclei, and its functional role as a cyclic AMP-responsive element-binding protein (CREB) kinase in high frequency stimulation (HFS)-induced LTP in the rat hippocampal CA1 region. CaMKIV was transiently activated in neuronal nuclei after HFS, and the activation returned to the basal level within 30 min. Phosphorylation of CREB, which is a CaMKIV substrate, and expression of c-Fos protein, which is regulated by CREB, increased during LTP. This increase was inhibited mainly by CaMK inhibitors and also by an inhibitor for mitogen-activated protein kinase cascade, although to a lesser extent. Our results suggest that CaMKIV functions as a CREB kinase and controls CREB-regulated gene expression during HFS-induced LTP in the rat hippocampal CA1 region.

Animals↗
PubMed2001

Amyloid beta protein activates PKC-delta and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia.

The increased accumulation of activated microglia containing amyloid beta protein (Abeta) around senile plaques is a common pathological feature in subjects with Alzheimer's disease (AD). Much less is known, however, of intracellular signal transduction pathways for microglial activation in response to Abeta. We investigated intracellular signaling in response to Abeta stimulation in primary cultured rat microglia. We found that the kinase activity of PKC-delta but not that of PKC-alpha or -epsilon is increased by stimulation of microglia with Abeta, with a striking tyrosine phosphorylation of PKC-delta. In microglia stimulated with Abeta, tyrosine phosphorylation of PKC-delta was evident at the membrane fraction without an overt translocation of PKC-delta. PKC-delta co-immunoprecipitated with MARCKS from microglia stimulated with Abeta. Abeta induced translocation of MARCKS from the membrane fraction to the cytosolic fraction. Immunocytochemical analysis revealed that phosphorylated MARCKS accumulated in the cytoplasm, particularly at the perinuclear region in microglia treated with Abeta. Taken together with our previous observations that Abeta-induced phosphorylation of MARCKS and chemotaxis of microglia are inhibited by either tyrosine kinase or PKC inhibitors, our results provide evidence that Abeta induces phosphorylation and translocation of MARCKS through the tyrosine kinase-PKC-delta signaling pathway in microglia.

Amyloid beta-Peptides↗
PubMed2001

Characterization of a vitamin B12 compound from unicellular coccolithophorid alga (Pleurochrysis carterae).

A unicellular coccolithophorid alga, Pleurochrysis carterae, contained 125.4 +/- 1.2 microg of vitamin B12 per 100 g dry cell weight of the lyophilized algal cells. A vitamin B12 compound was purified from the lyophilized algal cells and partially characterized. The silica gel 60 TLC and reversed-phase HPLC patterns of the purified pink-colored compound were identical to those of authentic vitamin B12, but not those of vitamin B12 analogues inactive for humans. When 22-week-old B12-deficient rats which excreted substantial amounts of methylmalonic acid (75.5 +/- 12.3 mg/day) in urine were fed the P. carterae (10 g per kg diet)-supplemented diet for 12 d, urinary methylmalonic acid excretion (as an index of vitamin B12 deficiency) of the rats became undetectable and hepatic vitamin B12 level of the rats was significantly increased.

Animals↗
PubMed2001

Inactive corrinoid-compound significantly decreases in Spirulina platensis grown in a cobalt-deficient medium.

Spirulina platensis NIES-39 was grown under open culture system in the presence or absence of CoSO(4) (12 microg/L) and/or vitamin B(12) (10 microg/L) to confirm whether CoSO(4) and/or vitamin B(12) stimulate or are essential for growth of the algal cells and for accumulation of vitamin B(12). The addition of CoSO(4) and/or vitamin B(12) could not affect both cell growth and cell yield of the alga. The amount of corrinoid-compound was increased significantly by the addition of CoSO(4) but not by vitamin B(12). A C18 reversed-phase HPLC pattern of the Spirulina corrinoid-compound increased by the addition of CoSO(4) was identical to that of authentic pseudovitamin B(12), which is inactive for human. These results indicate that the algal cells grown in the absence of CoSO(4) are suitable for use of human health foods because the inactive corrinoid-compound can be reduced significantly.

Chromatography, High Pressure Liquid↗
PubMed2001

Involvement of calcium-calmodulin protein kinase but not mitogen-activated protein kinase in light-induced phase delays and Per gene expression in the suprachiasmatic nucleus of the hamster.

It is known that Ca(2+)-dependent phosphorylation of cAMP response element binding protein (CREB) and the rapid induction of mPer1 and mPer2, mouse period genes in the suprachiasmatic nucleus (SCN) are associated with light-induced phase shifting. The CREB/CRE transcriptional pathway has been shown to be activated by calcium/calmodulin dependent kinase II (CaMKII) and mitogen-activated protein kinase (MAPK); however, there is a lack of evidence concerning whether the activation of CaMKII and/or MAPK elicited by photic stimuli are associated with the change in Per gene expression and behavioral phase shifting. In this experiment, we found there was an inhibitory effect by KN93, CaMKII inhibitor, on hamster Per1 and Per2 expression in the SCN and on phase delays in wheel running rhythm induced by light pulses. PD98059 and U0126, MAPK kinase inhibitors, however, affected neither light-induced Per1 and Per2 expression nor behavioral phase delays, even though PD98059 attenuated the light-induced phosphorylation of MAPK in the SCN. The present findings demonstrate that the light-induced activation of CaMKII plays an important role in the induction of Per1 and Per2 mRNA in the hamster SCN as well as phase shifting. These results suggest that gated induction of Per1 and/or Per2 genes through CaMKII-CREB/CRE accompanied with photic stimuli may be a critical step in phase shifting.

Animals↗
PubMed2001

Feeding dried purple laver (nori) to vitamin B12-deficient rats significantly improves vitamin B12 status.

To clarify the bioavailability of vitamin B12 in lyophylized purple laver (nori; Porphyra yezoensis), total vitamin B12 and vitamin B12 analogue contents in the laver were determined, and the effects of feeding the laver to vitamin B12-deficient rats were investigated. The amount of total vitamin B12 in the dried purple laver was estimated to be 54.5 and 58.6 (se 5.3 and 7.5 respectively) microg/100 g dry weight by Lactobacillus bioassay and chemiluminescent assay with hog intrinsic factor respectively. The purple laver contained five types of biologically active vitamin B12 compounds (cyano-, hydroxo-, sulfito-, adenosyl- and methylcobalamin), in which the vitamin B12 coezymes (adenosyl- and methylcobalamin) comprised about 60 % of the total vitamin B12. When 9-week-old vitamin B12-deficient rats, which excreted substantial amounts of methylmalonic acid (71.7(se 20.2) micromol/d) in urine, were fed the diet supplemented with dried purple laver (10 microg/kg diet) for 20 d, urinary methylmalonic acid excretion (as an index of vitamin B12 deficiency) became undetectable and hepatic vitamin B12 (especially adenosylcobalamin) levels were significantly increased. These results indicate that vitamin B12 in dried purple laver is bioavailable to rats.

Animals↗
PubMed2001

Characterization of vitamin B12 compounds from edible shellfish, clam, oyster, and mussel.

Vitamin B12 content of various edible shellfish was determined by both Lactobacillus leichmannii ATCC 7830 microbiological and intrinsic factor-chemiluminescence methods. The values determined by the microbiological method were 1.2-19.8 (M/C ratio) fold greater in the shellfish than the values determined by the chemiluminescence method. Vitamin B12 compounds were purified from most eaten shellfish, oyster (M/C, 1.5), mussel (M/C, 1.2), and short-necked clam (M/C, 2.7), and partially characterized. TLC and HPLC patterns of each red-colored vitamin B12 compound (M/C, 1.0-1.2) purified from these shellfish were identical to those of authentic vitamin B12. Although the higher values in the determination of vitamin B12 by the microbiological method may be due to the occurrence of vitamin B12-substitutive compounds, the edible shellfish would be excellent vitamin B12 sources judging from the values (> or = 6 micrograms/100 g) determined by the chemiluminescence method.

Animals↗
PubMed2001

Xenon inhibits but N(2)O enhances ketamine-induced c-Fos expression in the rat posterior cingulate and retrosplenial cortices.

Both nitrous oxide (N(2)O) and xenon are N:-methyl-D-aspartate receptor antagonists that have psychotomimetic effects and cause neuronal injuries in the posterior cingulate and retrosplenial cortices. We investigated the effect of xenon, xenon with ketamine, N(2)O, and N(2)O with ketamine on c-Fos expression in the rat posterior cingulate and retrosplenial cortices, a marker of psychotomimetic effects. Brain sections were prepared, and c-Fos expression was detected with immunohistochemical methods. A loss of microtubule-associated protein 2, a marker of neuronal injury, was also investigated. The number of Fos-like immunoreactivity positive cells by ketamine IV at a dose of 5 mg/kg under 70% N(2)O (128 +/- 12 cells per 0.5 mm(2)) was significantly more than those under 30% (15 +/- 2 cells per 0.5 mm(2)) and 70% xenon (2 +/- 1 cells per 0.5 mm(2)). Despite differences in c-fos immunoreactivity, there was no loss of microtubule-associated protein 2 immunoreactivity in any group examined. Xenon may suppress the adverse neuronal effects of ketamine, and combined use of xenon and ketamine seems to be safe in respect to neuronal adverse effects.

Animals↗
PubMed2001

Activation of Akt/protein kinase B contributes to induction of ischemic tolerance in the CA1 subfield of gerbil hippocampus.

Apoptosis plays an important role in delayed neuronal cell death after cerebral ischemia. Activation of Akt/protein kinase B has been recently reported to prevent apoptosis in several cell types. In this article the authors examine whether induction of ischemic tolerance resulting from a sublethal ischemic insult requires Akt activation. Sublethal ischemia gradually and persistently stimulated phosphorylation of Akt-Ser-473 in the hippocampal CA1 region after reperfusion. After lethal ischemia, phosphorylation of Akt-Ser-473 showed no obvious decrease in preconditioned gerbils but a marked decrease in nonconditioned gerbils. Changes in Akt-Ser-473 phosphorylation were correlated with changes in Akt activities, as measured by an in vitro kinase assay. Intracerebral ventricular infusion of wortmannin before preconditioning blocked both the increase in Akt-Ser-473 phosphorylation in a dose-dependent manner and the neuroprotective action of preconditioning. These results suggest that Akt activation is induced by a sublethal ischemic insult in gerbil hippocampus and contributes to neuroprotective ischemic tolerance in CA1 pyramidal neurons.

Androstadienes↗