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Biomedical subjects

K Onodera

Publications and source records attributed to K Onodera.

At least 37 records · Page 2Linked to original sources
PubMed2001

Antinociceptive effect of vitamin K2 (menatetrenone) in diabetic mice.

The antinociceptive effect of vitamin K2 (menatetrenone) in diabetic mice was examined using a tail-pressure test. Intraperitoneal injection of menatetrenone (10-100 mg/kg) produced a dose-dependent increase in the nociceptive threshold in diabetic mice. There was no significant difference between non-diabetic and diabetic mice in the menatetrenone-induced changes in the nociceptive threshold. The results suggest the therapeutical usefulness of menatetrenone for treating painful diabetic neuropathy and osteoporosis.

Analgesics↗
PubMed2001

Localization of metallothionein (MT) and expression of MT isoforms induced by cadmium in rat dental pulp.

We investigated the induction of metallothionein (MT) by cadmium (Cd) in the dental pulp of rat incisors. Time-course studies of MT mRNA expression after single Cd injection were observed by Northern-blot analysis. The isoform-specific expressions of MT mRNAs (MT-I, MT-II and MT-III) were observed using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Both MT-I and MT-II mRNA levels increased within 3 h, peaked at 3 h and then decreased. These findings demonstrated that MT-I and MT-II mRNA were rapidly induced by Cd in dental pulp. MT-III mRNA was constitutively expressed in rat dental pulp, but the expression level did not change by Cd treatment. The localization of MT protein in Cd-treated rat dental pulp was determined by immunohistochemical staining using anti-MT antibody against MT-I and MT-II. MT protein was localized in the specific cell type of odontoblasts (secretory odontoblasts and resting odontoblasts). In conclusion, it is likely that stained MT in the immunohistochemical study should be MT-I and/or MT-II. Furthermore, MT-I and/or MT-II in Cd-treated rat dental pulp was localized in odontoblasts, in which accumulation of Cd were reported. The cell-specific synthesis of MT may be associated with its metal storage and detoxification role in dental tissues.

Animals↗
PubMed2001

Bisphenol A enhances cadmium toxicity through estrogen receptor.

To clarify the action of estrogenic endocrine disruptors on cadmium (Cd)-induced metallothionein (MT) synthesis in the liver, we investigated the effects of bisphenol A (BPA) on hepatic MT-I mRNA expression and MT contents after Cd injection. Liver damage after Cd injection was assessed by measuring glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) activities in the serum. It was found that BPA reduced the Cd-induced expression of MT-I mRNA and MT protein in the liver. The administration of tamoxifen, an estrogen receptor antagonist, prevented the reduction of hepatic MT content by PA. Moreover both the GPT and GOT activities of the BPA-treated groups were higher than those of the control groups. These findings suggest that BPA reduced hepatic MT synthesis after Cd injection via the estrogen receptor which resulted in increased damage to the liver.

Alanine Transaminase↗
PubMed2001

Age-related differences in forced walking stress-induced analgesia in mice.

We investigated the effects of aging on forced walking stress-induced analgesia using a formalin-induced paw licking test in male mice. Exposure to forced walking stress for 6 h showed forced walking stress-induced analgesia in all mice aged 4, 24 and 48 weeks in the second phase (10-30 min), but not in the first phase (0-10 min). In the second phase, the degree of stress-induced analgesia was age-dependent (4 > 24 > 48 weeks). LY-235959, a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, blocked forced walking stress-induced analgesia in mice aged 4 and 24 weeks, but not in those aged 48 weeks. Naloxone did not antagonize forced walking stress-induced analgesia in mice in any of the age groups. The present study suggests that the degree of forced walking stress-induced analgesia depends on the age of mice and confirms previous findings that forced walking stress-induced analgesia is involved in the nonopioid system via NMDA receptors.

Aging↗
PubMed2000

Antinociceptive effect induced by intraperitoneal administration of vitamin K2 (menatetrenone) in ICR mice.

The antinociceptive effect of vitamin K2 (menatetrenone) in mice was examined using tail-flick and formalin test. Menatetrenone at doses of 10, 50 and 100 mg/kg, i.p. produced a dose-dependent and significant inhibition of the tail-flick response in mice. Menatetrenone (50 and 100 mg/kg, i.p.) had no significant effect on the duration of the first phase of the formalin-induced flinching. However, menatetrenone (100 mg/kg, i.p.) significantly inhibited the second phase of the formalin-induced flinching. I.p. administration of menatetrenone (100 mg/kg) significantly reduced the duration of nociceptive responses induced by i.t. injection of bradykinin, but not of substance P, prostaglandin E2 or N-methyl-D-aspartate (NMDA). These present data suggest that i.p. pretreatment with menatetrenone produced dose-dependent antinociceptive effect in mice. This effect may be, at least in part, mediated by the inhibition of bradykinin dependent nociceptive transmission in the spinal cord.

Analgesics↗
PubMed2000

One enhancer mediates mafK transcriptional activation in both hematopoietic and cardiac muscle cells.

Members of the small Maf family of transcription factors play important roles in hematopoiesis. Using transgenic assays, we discovered a tissue-specific enhancer 3' to the mafK gene. This enhancer directs mafK transcription in hematopoietic as well as in developing cardiac muscle cells, and was thus designated the hematopoietic and cardiac enhancer of mafK (HCEK). Only two of four GATA consensus motifs identified within HCEK contributed to enhancer activity, and both of these sites were required for both cardiac and hematopoietic transcriptional activation. The expression profile of MafK significantly overlapped that of GATA-1 in hematopoietic cells and of GATA-4/-6 in cardiac tissues. Each of these GATA factors bound with high specificity to both of the critical GATA sites in HCEK. Hence, the mafK gene is regulated by different GATA proteins in the hematopoietic and cardiac compartments through the same two GATA-binding sites in HCEK. These data provide the first in vivo demonstration that distinct members of a related transcription factor family activate the tissue-specific expression of a single target gene using the same cis-regulatory element.

Animals↗
PubMed2000

Primary afferent synaptic responses recorded from trigeminal caudal neurons in a mandibular nerve-brainstem preparation of neonatal rats.

1. Whole-cell patch-clamp recordings were made from the neurons in the superficial trigeminal caudal nucleus (substantia gelatinosa) visually identified in a parasagittal brainstem slice of neonatal rat with the mandibular nerve attached. 2. Stimulation of the mandibular nerve at 0.03 Hz evoked compound excitatory postsynaptic potentials (EPSPs) or currents (EPSCs) in trigeminal caudal neurons. When stimulated at higher frequency (> 0.5 Hz), compound synaptic responses were largely attenuated and a small component remained. This component had a monosynaptic nature, following high-frequency stimulation (33-50 Hz) with a stable synaptic latency. 3. The N-methyl-D-aspartate (NMDA) receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 microM) largely attenuated the slow polysynaptic EPSCs. The AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) largely attenuated monosynaptic EPSCs, but only weakly attenuated slow polysynaptic EPSCs. Simultaneous application of CNQX and D-AP5 completely abolished EPSCs. The monosynaptic EPSCs isolated by repetitive stimulation had both NMDA and non-NMDA components. 4. Monosynaptic EPSCs having high threshold had a relatively long latency. During repetitive stimulation (0.5-5.0 Hz), EPSCs having high threshold and long latency underwent a stepwise potentiation in an activity-dependent manner. The conduction velocity estimated for these EPSCs fell into the range of C-fibres. The activity-dependent potentiation was observed for both non-NMDA and NMDA EPSCs and was accompanied by a significant decrease in the coefficient of variation of EPSC amplitude. 5. We suggest that the activity-dependent potentiation of EPSCs is induced presynaptically and that it may underlie the wind-up phenomenon, an activity-dependent hyperexcitability of the primary afferent C-fibres.

2-Amino-5-phosphonovalerate↗
PubMed2000

Perinatal synthetic lethality and hematopoietic defects in compound mafG::mafK mutant mice.

Prior studies exploring the mechanisms controlling erythroid gene regulation implicated MARE (Maf recognition element) cis-elements as crucial to the transcriptional activity of many erythroid genes. Numerous transcription factors can elicit responses through MAREs, including not only the AP-1 family proteins, but also a growing list of factors composed of Cap-N-Collar (CNC)-small Maf heterodimers. While these factors can activate transcription from MAREs in co-transfection assays, mouse germline mutations in cnc genes tested to date have failed to reveal primary erythroid phenotypes. Here we report that after combining the mafK and mafG targeted null alleles, mutant animals display several synthetic phenotypes, including erythroid deficiencies. First, compound homozygous small maf gene mutants survive embryogenesis, but die postnatally. Secondly, compound mutant animals develop severe neurological disorders. Thirdly, they exhibit an exacerbated mafG deficiency in megakaryopoiesis, specifically in proplatelet formation, resulting in profound thrombocytopenia. Finally, the compound mutant animals develop severe anemia accompanied by abnormal erythrocyte morphology and membrane protein composition. These data provide direct evidence that the small Maf transcription factors play an important regulatory role in erythropoiesis.

Anemia↗
PubMed2000

Functional correlation of GABA(A) receptor alpha subunits expression with the properties of IPSCs in the developing thalamus.

GABA(A) receptor alpha1 and alpha2 subunits are expressed differentially with ontogenic period in the brain, but their functional roles are not known. We have recorded GABA(A) receptor-mediated IPSCs from laterodorsal (LD) thalamic relay neurons in slices of rat brain at various postnatal ages and found that decay times of evoked IPSCs and spontaneous miniature IPSCs undergo progressive shortening during the first postnatal month. With a similar time course, expression of transcripts and proteins of GABA(A) receptor alpha2 subunit in LD thalamic region declined, being replaced by those of alpha1 subunit. To further address the causal relationship between alpha subunits and IPSC decay time kinetics, we have overexpressed GABA(A) receptor alpha1 subunit together with green fluorescent protein in LD thalamic neurons in organotypic culture using recombinant Sindbis virus vectors. Miniature IPSCs recorded from the LD thalamic neurons overexpressed with alpha1 subunit had significantly faster decay time compared with control expressed with beta-galactosidase. We conclude that the alpha2-to-alpha1 subunit switch underlies the developmental speeding in the decay time of GABAergic IPSCs.

Animals↗
PubMed2000

Fibronectin-mononuclear cell interactions regulate type 1 helper T cell cytokine network in tolerant transplant recipients.

Fibronectin (FN), expressed primarily by macrophages, endothelial cells, and smooth muscle cells, represents an integral feature of the rejection response in transplant recipients. Here we demonstrate a unique pattern of cellular FN expression in rat recipients of cardiac allografts rendered tolerant in an infectious manner with either nondepleting CD4 mAb or regulatory spleen cells. Unlike in rejecting controls, cellular FN in tolerant hosts was restricted to the graft vessels and no vascular cell adhesion molecule-1 or intercellular adhesion molecule-1 expression could be found, supporting the role of FN in leukocyte sequestration at the graft site. The lack of myocardial FN in tolerant rats, despite dense macrophage infiltration, correlated with profound depression of Th1 (interleukin-2 and interferon-gamma) cytokines. Treatment with CD4-depleting mAb prevented tolerance induction and restored myocardial expression of FN in parallel with marked increase in the expression of interleukin-2 and interferon-gamma mRNA/protein. Furthermore, connective segment-1 peptide-facilitated adjunctive blockade of FN-alpha4beta1 interactions in recipients conditioned with CD4 depleting mAb, significantly depressed intragraft expression of interleukin-2 and interferon-gamma mRNA/protein. Hence, the lack of FN associated with infiltrating leukocytes plays an important role in the maintenance of tolerance in transplant recipients by depressing local expression of Th1 cytokines that otherwise facilitate acute graft rejection.

Animals↗
PubMed2000

A histopathological study of lymphoepithelial island formation in labial salivary glands in patients with primary Sjögren's syndrome.

The proliferative status of lymphoepithelial islands in the labial salivary glands of primary Sjögren's syndrome (pSS) patients was investigated by counting the number of argyrophilic nucleolar organizer regions (AgNORs) in epithelial cells constituting the islands. The islands were classified into four groups and evaluated in terms of total area and three discrete zones of the islands. In each pSS group, the mean AgNOR number per total island epithelial cell nucleus was significantly higher than in control ductal epithelial cells. The zonal AgNOR number fluctuated during the process of island formation but became more uniform as the islands developed. Furthermore, statistically significant trends among the four pSS groups were observed in the ratio of T lymphocytes, B lymphocytes and plasma cells surrounding the islands. The results indicated that the islands are highly proliferative once island formation begins and that zonal island cell proliferation may be associated with the inflammatory cells.

Adult↗
PubMed2000

Long-term potentiation of primary afferent neurotransmission at trigeminal synapses of juvenile rats.

Primary afferent monosynaptic and polysynaptic excitatory postsynaptic currents (EPSCs) were recorded from brainstem trigeminal neurons by stimulation of the mandibular nerve attached to the brainstem preparation of juvenile rats. A high-frequency conditioning stimulus induced long-term potentiation (LTP) of high-threshold EPSCs in the majority of trigeminal caudal neurons in substantia gelatinosa, where both A- and C-fibres terminate. However, the same conditioning stimulus did not potentiate low-threshold EPSCs in caudal neurons or EPSCs recorded from neurons in the middle part of trigeminal interpolar nucleus, where C-fibres rarely terminate. LTP in caudal neurons could be induced after blocking N-methyl-D-aspartate (NMDA) receptors with D(-)-2-amino-5-phosphonopentanoic acid (D-AP5, 50 microM), after postsynaptic loading of the Ca2+ chelator BAPTA (10 mM), or even after completely blocking excitatory transmission with kynurenic acid during conditioning. However, LTP was blocked by the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine (1 mM). We suggest that LTP of the trigeminal primary afferent EPSCs is induced preferentially in the C-fibre inputs and that the induction mechanism involves metabotropic glutamate receptors, possibly at the presynaptic terminals.

2-Amino-5-phosphonovalerate↗
PubMed2000

Differential involvement of opioid receptors in stress-induced antinociception caused by repeated exposure to forced walking stress in mice.

We examined the effects of repeated exposure to forced walking stress for 6 h once a day for 0, 6 and 9 consecutive days on formalin-induced paw licking in mice. In each observation period, stress-induced antinociception (SIA) was observed only in the late phase (from 10 to 30 min), but not in the early phase (from 0 to 10 min) of formalin-induced paw licking in mice. Moreover, it was hard to develop tolerance even by daily exposure to stress for 6 days, although SIA for 9 days decreased compared with those for 0 and 6 days. Naloxone (10 mg/kg), an opioid-receptor antagonist, was effective in reducing the SIA induced by forced walking stress for 6 days and/or 9 days, but not for 0 days. Furthermore, the experiments with selective opioid-receptor antagonists, beta-funaltrexamine (mu) naltrindol (delta), or nor-binaltorphimine (kappa) demonstrated that SIA induced by forced walking stress for 9 successive days may be mediated through opioid delta- and kappa-receptors. Finally, although SIA seemed to be a unitary phenomenon, the present results strengthened the idea that SIA is induced by exposure to forced walking stress with characteristics dependent on the duration of exposure.

Animals↗
PubMed2000

[Animal models of 'anxiety'].

Many animal models of anxiety have been reported; for example, Geller-type or Vogel-type anticonflict tests and ethologically based tests without punishment such as a light/dark test, a hole-board test, a social interaction test, an elevated plus-maze test and so on. These models were pharmacologically validated by the evidence that clinically useful anxiolytic benzodiazepines were active, but activities of serotonergic anxiolytics in these models were inconsistent. These models might measure a mixture of several types of anxiety. Many disorders of anxiety are classified in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) and several disorders can not be treated with benzodiazepines very well. Animal models to evaluate the drugs for the benzodiazepine-untreatable disorders are needed. Graeff et al. performed studies to measure inhibitory avoidance latency from an enclosed arm to open arms and escape latency from the open arms to the enclosed arm as parameters of conditioned and unconditioned fears, respectively, in the elevated T-maze in rats. The latter was suggested for use in the evaluation of drugs efficacious on a panic disorder. A marble burying test as an animal model for an obsessive-compulsive disorder was also reported. However, establishment of the models for these disorders remains for future investigations.

Animals↗
PubMed2000

[The 1999 domestic state of development of anti-asthma].

According to the "Guideline for Diagnosis and Treatment of Asthma" established by the Japanese Society of Allergy in 1998, inhaled adrenergic beta 2 agonists and inhaled corticosteroids are recommended for treatment of asthma. Thereafter, the development of new drugs for the treatment of asthma has begun changing. The concepts upon which the development of investigational drugs for asthma are based include improvements of drug delivery systems (ease of use, long-acting preparations, fewer side-effects), device design and appropriate auxiliary instrumentation. Moreover, chronic asthma has come to be recognized as an inflammatory disease of airway mucosa. At present, various antiallergic compounds such as tachykinin, leucotrien, PAF antagonists and others are under investigation thanks to the identification of new chemical mediators of airway inflammation and studies have progressed to the synthesis and manufacturing of new pharmaceuticals with antagonistic action. Thus, this review classified and introduced various new investigational anti-asthma and further describes the structure-activity relationships of beta 2 agonists and inhaled corticosteroids.

Adrenergic beta-Agonists↗
PubMed2000

[Sensitive determination of vitamin K analogues in biological samples by high-performance liquid chromatography using platinum catalyst reduction and electrochemical detection].

To investigate the physiological roles of vitamin K analogues in bone metabolism, especially in osteoporosis, we have developed a sensitive and simple analysis system for vitamin K analogues in the serum and bone. After the separation of vitamin K analogues on a reversed-phase column, the analogues were reduced once in a platinum catalyst reduction column on-line and then monitored quantitatively by electrochemical detector (EICOM ECD-300) operated in the oxidation mode (+0.6 V vs. Ag/AgCl). The detection limits at a signal-to-noise ratio of 3 were 2-10 pg for vitamin K analogues. We also investigated the extraction procedures for the vitamin K analogues from serum and bone. Quantitative recoveries from serum and bone were obtained in the range of 80-101% for vitamin K analogues. We could determine both the circulating vitamin K levels in osteoporotic patients and the vitamin K contents in trabecular and cortical bone of osteoarthritis.

Animals↗
PubMed2000

Effects of intravenous theophylline, aminophylline and ethylenediamine on antigen-induced bronchoconstriction in guinea pigs.

The antiasthmatic effect of i.v. injection of theophylline was compared with that of aminophylline by using an antigen-induced bronchoconstriction model in sensitized guinea pigs. Both theophylline and aminophylline showed dose-dependent inhibition of antigen-induced bronchoconstriction. Statistically significant differences were observed at theophylline doses of 20 and 40 mg/kg and at aminophylline doses of 25 and 50 mg/kg. Thus, antiasthmatic effects of both drugs appeared to be similar. In addition, intravenous ethylenediamine did not influence either airflow in normal guinea pigs or bronchoconstriction induced by antigen at doses up to 30 mg/kg. In conclusion, the ethylenediamine in aminophylline may not influence the antiasthmatic action of theophylline, and the therapeutic effects of theophylline and aminophylline are suggested to be similar.

Aminophylline↗