Search PubMed⌕ Search

Biomedical subjects

K Onodera

Publications and source records attributed to K Onodera.

At least 109 records · Page 6Linked to original sources
PubMed1997

Therapeutic doses of theophylline exert proconvulsant effects in developing mice.

We studied the effect of therapeutic doses of theophylline on electrically-induced convulsions in developing mice. A theophylline dose as small as 3 mg/kg increased seizure susceptibility of 21-day-old mice, but not of 42-day-old mice. These findings were consistent with clinical reports that theophylline at the therapeutic blood concentrations occasionally induced convulsions in children. The age-dependent proconvulsant effect of theophylline was well inhibited by phenobarbital (PB), dose-dependently, but not by other well-established antiepileptic drugs (AEDs). PB may be a good choice of AED in patients with bronchial asthma and seizure disorders, if PB is indicative for their seizure types. The proconvulsant effect of theophylline in 21-day-old mice was counteracted by not only an adenosine A1 agonist, but also an NMDA antagonist and a histamine H3 antagonist. Several studies have established that the proconvulsant effect of theophylline intoxication is mainly due to the blockade of adenosine A1 receptors. The present findings suggested that the proconvulsant properties of therapeutic doses of theophylline in developing period were different from those of theophylline intoxication. Combination of therapeutic doses of theophylline and centrally-acting histamine H1 antagonists showed proconvulsant effects even in 42-day-old mice, suggesting that peripherally acting histamine H1 antagonists, such as astemizole, evastine and epinastine, were much safer than centrally acting histamine H1 antagonists for patients with both allergy and seizure history.

Aging↗
PubMed1997

Oxidized LDLs but not native LDLs augment Ba2+ currents through L-type Ca2+ channels of the A7r5 smooth muscle-derived cell line.

The whole-cell patch-clamp method was used on A7r5 smooth muscle-derived cell line, and Ba2+ currents through Ca2+ channels were recorded. The A7r5 cells showed voltage-dependent, long-lasting Ba2+ currents which were markedly inhibited by nifedipine (10 microM). The magnitude of the maximum Ba2+ current (IBa(max)) was augmented by an application of dbcAMP (1 mM), but not affected by TPA (80 nM). Noradrenaline (NA) at 100 microM caused an increase in the IBa(max) by 19.7% in the presence of phentolamine (10 microM). This effect was cancelled by Rp-cAMPs (10 microM). In the presence of propranolol (10 microM), NA tended to reduce the IBa(max). Application of Ox-LDLs at 100 microg protein/ml caused an increase in the IBa(max) by 15.7%, whereas native LDLs did not change the IBa(max). Rp-cAMPs was ineffective to the Ox-LDL action on the IBa(max). In the presence of Ox-LDLs, NA augmented the IBa(max) by 21.4% in the presence of phentolamine. These results suggest that Ox-LDLs activate L-type Ca2+ channels of A7r5 cells by a mechanism independent of cAMP/PKA signalling.

Aorta↗
PubMed1997

Upstream and downstream of erythroid transcription factor GATA-1.

All mature blood lineages in the peripheral circulation are derived from pluripotent haematopoietic stem cell. Progressive lineage-restriction of this stem cell is executed, in part, by the interplay and cross-talk between a host of lineage-restricted as well as ubiquitous transcription factors. To elucidate the regulatory mechanisms underlying the erythroid gene regulation, it is essential to understand how individual transcription factors contribute to the regulation of specific target genes, and how these erythroid transcription factor genes are regulated in turn. These key issues of mammalian development have been addressed by examining the activities controlling the prototype transcription factor, GATA-1. The transcriptional regulation of GATA-1 has been intensively investigated, thereby leading to the identification of its developmental stage-specific regulatory sequences. Loss-of-function mutant animals, combined with specific marking of the primitive and definitive erythroid lineages have also shed new insight into how GATA-1 activity is required in vivo at specific developmental stages. Procedures have also been developed for ascertaining whether or not the GATA-1 protein actually binds in vivo to regulatory GATA motifs in candidate target genes. Application of a similar multifaceted approach should enable investigators to examine the physiological roles that any transcription factor might play in vivo during the differentiation of any well defined cell lineage.

Animals↗
PubMed1997

Effect of cocaine on the histaminergic neuron system in the rat brain.

To examine the effect of cocaine on the brain histamine neuron system, histamine levels and histamine N-methyltransferase activity in the rat brain were measured after the administration of cocaine. Moreover, we examined the effect of L-histidine on cocaine-induced wheel-running behavior. The administration of cocaine (20 mg/kg) increased histamine levels and histamine N-methyltransferase activity in the striatum, nucleus accumbens, and amygdala 1 h later. The pretreatment with L-histidine (350 and 700 mg/kg) inhibited the cocaine (20 mg/ kg)-induced increase of wheel-running activity in a dose-dependent manner. These findings suggest that cocaine activates the brain histamine neuron system, which may play the role of inhibiting the cocaine-induced wheel-running behavior.

Amygdala↗
PubMed1997

Thrombin stimulates production of transforming growth factor-beta by cultured human mesangial cells.

Fibrin formation within the glomeruli occurs in various forms of human and experimental glomerulonephritis and it may play an important role in progressive glomerular injury. Transforming growth factor-beta (TGF-beta) has been shown to participate in the glomerular accumulation of extracellular matrix in glomerulonephritis. We investigated whether thrombin, an important coagulation factor, could modulate the production of TGF-beta by cultured human mesangial cells (HMC). TGF-beta levels in the culture supernatants were measured by ELISA using a specific antibody. The TGF-beta concentration was significantly increased by incubation of HMC with thrombin in a time-dependent manner. The stimulating effect of thrombin on TGF-beta was inhibited by addition of hirudin (a natural thrombin inhibitor) and argatroban (a synthetic thrombin inhibitor). In addition DFP-inactivated thrombin, which has no enzymatic activity, did not stimulate TGF-beta production. A protein kinase C inhibitor (H7) and a tyrosine kinase inhibitor (herbimycin A) also inhibited thrombin induced TGF-beta production. These findings suggested that thrombin may modulate the synthesis of TGF-beta via protein kinase C- and tyrosine kinase-dependent mechanisms in cultured HMC. Thus thrombin may participate in the accumulation of extracellular matrix in glomeruli through the augmentation of TGF-beta production.

Cells, Cultured↗
PubMed1997

Conserved structure, regulatory elements, and transcriptional regulation from the GATA-1 gene testis promoter.

Transcription factor GATA-1 was first identified in erythroid cells, but was later shown to also be expressed in Sertoli cells of the mouse testis. GATA-1 transcription in testis initiates from a different first exon (exon IT) than the erythroid mRNA (transcribed from exon IE). To begin to address the question of how expression of GATA-1 might be differentially regulated in Sertoli and erythroid cells, we have cloned and determined the structure of the IT promoters of both the rat and mouse GATA-1 genes. The transcription regulatory mechanism(s) controlling the synthesis of exon IT-derived mRNA was investigated by transfection of wild-type and mutant reporter genes, with and without co-transfected GATA factor expression plasmids, into either fibroblasts or Sertoli cell lines. Two GATA binding sites in the IT promoter were found to be required for GATA factor-mediated activation in fibroblasts: GATA-IT-directed reporter gene expression was activated only after co-transfection with GATA-1, implying that transcriptional activation of GATA-1 in the testis might be at least partially mediated through these GATA regulatory elements. We also found that the endogenous GATA-1 gene was silent in primary culture and two different Sertoli cell lines, and that the repression of co-transfected GATA-1 reporter genes could not be relieved by forced expression of GATA-1 in Sertoli cells. Thus the GATA-IT promoter may be under the control of a regulatory network in Sertoli cells which involves both positive and negative regulation of transcription, and conserved GATA motifs found in the IT promoter may be required for transducing these effects.

Animals↗
PubMed1997

Generalization of D-, L- and DL-chlorpheniramine and zolantidine to the discriminative stimulus effects of cocaine and methamphetamine.

We recently demonstrated that some H-antagonists have cocaine or methamphetamine-like discriminative stimulus effects. In the present study, the effects of optical isomers of chlorpheniramine (D-, L- and DL-forms) on the discriminative stimulus effects of cocaine and methamphetamine were examined in rats trained to discriminate between cocaine (10.0 mg/kg) or methamphetamine (1.0 mg/kg) and saline, to determine whether these effects of H1-antagonists are mediated by the blockade of H-receptors. In generalization tests with optical isomers of chlorpheniramine, the D-, L- and DL-forms all completely generalized to the discriminative stimulus effects of cocaine, but did not generalize to those of methamphetamine. Dose-generalization by the optical isomers of chlorpheniramine to the discriminative stimulus effects of cocaine did not correlate with the H-antagonistic potency of these drugs. These results suggest that all of the optical isomers of chlorpheniramine have cocaine-like discriminative stimulus effects, but that these effects are not mediated by H1-receptor blockade. On the other hand, the H2-antagonist, zolantidine, generalized to the discriminative stimulus effects of methamphetamine, but not to those of cocaine, suggesting that zolantidine may have methamphetamine-like discriminative stimulus effects. In the present study, GBR12909 (dopamine uptake inhibitor) completely generalized to the discriminative stimulus effects of cocaine, but not to those of methamphetamine, whereas apomorphine (dopamine receptor agonist) generalized more potently to the discriminative stimulus effects of methamphetamine than to those of cocaine. These findings imply that although the dopaminergic system plays an important role in the discriminative stimulus effects of both cocaine and methamphetamine, there may be differences between their effects.

Animals↗
PubMed1997

The effect of methamphetamine on histamine release in the rat hypothalamus.

In the present study, the effect of methamphetamine (MAP) on histamine (HA) release measured by in vivo brain microdialysis in the rat hypothalamus was investigated. Administration of MAP (3 mg/kg) significantly increase HA release from 40 to 160 min after the injection. This finding suggests that a moderate dose of MAP activates the hypothalamic HA neuron system, which may be related to effects of MAP on intrinsic biological rhythms.

Animals↗
PubMed1997

A case of the calcium pyrophosphate dihydrate (CPPD) deposition disease without condylar destruction of the temporomandibular joint.

The case of calcium pyrophosphate dihydrate (CPPD) deposition disease, which occurred at a rare site in the temporomandibular joint (TMJ), is presented. A 48-year-old woman noted swelling in the preauricular area of her left cheek, which restricted her mouth opening. Radiological examination revealed a radiopaque lesion in the posterior and medial area of the left space of the TMJ. During the operation, the superior joint space was entirely filled with a solid and whitish-gray mass of chalky appearance. The lesion was partly attached to the retrodiscal tissue without any destructive change around the condyle and mandibular fossa. Histological examination revealed the foci of amorphous crystalline material to contain rhomboidal, rod and needle shaped crystals, which had cartilaginous tissue in the dense fibrous background admixed with chronic inflammatory cells and foreign body-type giant cells. The crystals were positive for von Kossa's stain and spectral peaks for phosphorus and calcium were evident by electron probe microanalysis, thus suggesting the presence of CPPD.

Calcium Pyrophosphate↗
PubMed1997

Structure of human chromosome 21--for an understanding of genetic diseases including Down's syndrome.

We do not intend to give information about the structure of human chromosome 21 in detail but to give a kind of perspective of the present status of our knowledge about human chromosome 21 in this article. Recent development of molecular biology has changed revolutionarily the status of our knowledge of the human chromosome in general. Therefore we will choose a few aspects of the development in this field and want to discuss how we are able to use such information to understand the genetic diseases including Down's syndrome.

Animals↗
PubMed1997

The effect of haloperidol on the histaminergic neuron system in the rat brain.

In this study, the effect of haloperidol on histamine (HA) levels, histidine decarboxylase (HDC) activities and the bindings of [3H]-(R)-alpha-methylhistamine ([3H]-(R)-alpha-MeHA) to histamine H3 receptors were investigated in the rat brain. Administration of 10 mg/kg of haloperidol decreased HA levels in the rat striatum and diencephalon, but increased HDC activities in rat striatum and diencephalon, although that of 5 mg/kg did not change them. Meanwhile, haloperidol inhibited the bindings of [3H]-(R)-alpha-MeHA to H3 receptor sites in the rat striatal membrane with a Ki value of 10.5 +/- 0.45 microM. These findings suggest that only a high dose of haloperidol increases HA synthesis and release as a histamine H3 receptor antagonist in the rat brain.

Animals↗
PubMed1997

Biological activities of novel zaragozic acids, the potent inhibitors of squalene synthase, produced by the fungus, Mollisia sp. SANK 10294.

Four novel zaragozic acids, F-10863A, B, C and D, were isolated from a culture broth of the fungus Mollisia sp. SANK 10294. F-10863 compounds contain a 4,6,7-trihydroxy-2,8-dioxyobicyclo-[3.2.1]octane-3,4,5-tricarboxyl ic acid core like previously reported zaragozic acids, but the structures of the side chains are different. Recently, it was found that F-10863A is identical to zaragozic acid D3, while the other three are novel compounds. F-10863 compounds are potent inhibitors of squalene synthase like previously reported zaragozic acids, and, furthermore, they exhibit serum cholesterol-lowering activity in vivo.

Animals↗
PubMed1997

[Renal lesions of rats induced by antibodies to cultured rat glomerular epithelial cells and mesangial cells].

Renal lesions of rats induced by antibodies to cultured rat glomerular epithelial cells (GEC) and mesangial cells (GMC) were studied. Antibodies to cultured rat GEC and GMC were produced by immunization of rabbits with GEC and GMC respectively. The rats injected with anti-GEC antibody showed a small amount of urinary protein, glomerular deposition of rabbit IgG and subepithelial dense deposits observed by electron microscopy. Proteinuria was suppressed in the rats in which complement was depleted with cobra venom factor. Western blot analysis demonstrated a band of 200 KD in GEC lysates reacted with anti-GEC antibody. The rats injected with anti-GMC antibody showed little urinary protein, glomerular deposition of rabbit IgG and mesangial dense deposits. Western blot analysis demonstrated two bands of 43 and 14 KD in GMC lysates reacted with anti-GMC antibody. These data showed that the injection of anti-GEC antibody or anti-GMC antibody induced similar lesions to passive Heymann nephritis and anti Thy 1.1 nephritis. This study suggested that antigenicity of structural glomerular cells is important as the antigens of glomerulonephritis.

Animals↗
PubMed1996

Presynaptic calcium current modulation by a metabotropic glutamate receptor.

Metabotropic glutamate receptors (mGluRs) regulate transmitter release at mammalian central synapses. However, because of the difficulty of recording from mammalian presynaptic terminals, the mechanism underlying mGluR-mediated presynaptic inhibition is not known. Here, simultaneous recordings from a giant presynaptic terminal, the calyx of Held, and its postsynaptic target in the medial nucleus of the trapezoid body were obtained in rat brainstem slices. Agonists of mGluRs suppressed a high voltage-activated P/Q-type calcium conductance in the presynaptic terminal, thereby inhibiting transmitter release at this glutamatergic synapse. Because several forms of presynaptic modulation and plasticity are mediated by mGluRs, this identification of a target ion channel is a first step toward elucidation of their molecular mechanism.

Aminobutyrates↗
PubMed1996

Centrally acting histamine H1 antagonists promote the development of amygdala kindling in rats.

We studied the effect of histamine H1 antagonists on the development of amygdala kindling, an experimental model of epilepsy, in rats. The centrally acting histamine H1 antagonists including pyrilamine (mepyramine) and ketotifen showed an acceleration in the rate of electrical stimulation to develop fully kindled convulsive seizures. On the contrary, epinastine, a histamine H1 antagonist which scarcely enters the brain, showed no acceleration. These findings suggest that the central histaminergic neuron system plays an inhibitory role on the seizure development through central histamine H1 receptors.

Amygdala↗
PubMed1996

The effect of methamphetamine on histamine level and histidine decarboxylase activity in the rat brain.

To examine biochemical changes in the brain histamine (HA) neuron system after acute and chronic administrations of methamphetamine (MAP), HA levels and histidine decarboxylase (HDC) activities in the rat cortex, striatum, diencephalon, midbrain, pons-medulla and cerebellum were measured. In the cortex and striatum, acute administration of MAP (1 and 3 mg/kg) increased HA levels 1 h later. Acute administration of MAP (10 mg/kg) and chronic administration of MAP (3 mg/kg) for 21 days also increased HA levels and HDC activities in the cortex and striatum I h after the last injection. In the diencephalon, acute administration of MAP (3 and 10 mg/kg) and chronic administration of MAP (3 mg/kg) decreased HA level 1 h after the last injection, but chronic administration of MAP (3 mg/kg) increased HDC activity 1 h after the last injection. There were no significant changes in HA levels and HDC activities in other regions after acute and chronic administrations of MAP. These findings suggest that MAP may activate the brain HA neuron system, although MAP acts more strongly on the cortex and striatum than on the diencephalon.

Animals↗
PubMed1996

Induction of "infectious" tolerance to MHC-incompatible cardiac allografts in CD4 monoclonal antibody-treated sensitized rat recipients.

LBNF1 heart grafts are rejected in an accelerated manner within 36 h by LEW rats that have been sensitized with Brown Norway rat skin grafts on day -7. Treatment with RIB-5/2, a CD4-nondepleting mAb (10 doses of 5 mg/rat/day, i.v., from day -7 to day +21) abrogated rejection at <36 h and produced indefinite (>200 days) cardiac allograft survival. Transplantation tolerance in this model developed within several weeks, and during the maintenance phase (>100 days) it was associated with diminished host circulating allo-Ab responses and induction of peripheral allospecific T cell unresponsiveness both in vitro and in vivo. Tolerant cells in mAb-treated hosts could disable naive or alloimmune cells, so that they failed to trigger graft rejection. Moreover, donor-specific and organ-nonspecific tolerance could be adoptively transferred by spleen cells alone into new sets of primary (100%) and secondary (>40%) test recipients. CD4+ T cells were instrumental for the induction of such readily transferable tolerance. The first and second generation suppressive regulatory cells were also critical for the inhibition of allograft recognition by normal or even alloimmune cells. Hence, the features of an "infectious" tolerance pathway to minor histocompatibility-mismatched skin grafts, originally described in thymectomized mice, may be applied to the euthymic primed rats rendered tolerant to fully MHC-incompatible vascularized organ allografts. Such reprogramming of host cell-mediated regulatory mechanisms following CD4-targeted therapy adds to our appreciation of the potential utility and applicability of infectious tolerance in transplant recipients treated with a perioperative course of CD4-targeted monotherapy.

Adoptive Transfer↗