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Biomedical subjects

K Onodera

Publications and source records attributed to K Onodera.

At least 73 records · Page 4Linked to original sources
PubMed1999

Effects of forced walking stress on formalin-induced paw licking in mice.

This study examined the effects of exposing mice to forced walking stress on formalin-induced paw licking. At each observation period (0.5-6 h) after exposure to forced walking stress, a significant antinociceptive effect (stress-induced analgesia, SIA) was observed only in the second phase (from 10 to 30 min), but not in the first phase (from 0 to 10 min) of formalin-induced paw licking in mice. The present data showed that SIA induced by exposure to forced walking stress was dependent on duration of the stress (0.5-4 h). SIA was dose-dependently antagonized by the NMDA receptor antagonist dizocilipine (0.01-0.04 mg/kg) but not by naloxone (10 mg/kg). Thus, the present results suggest that exposure to forced walking stress could cause SIA which may be involved in the nonopioid system via NMDA receptors.

Analgesia↗
PubMed1999

Involvement of spinal delta 1-opioid receptors in forced walking stress-induced antinociception in the tail-flick test in mice.

The purpose of this study was to elucidate the involvement of spinal delta-opioid receptor subtypes in forced walking stress-induced antinociception mice. We first confirmed that forced walking stress produced walking duration-dependent antinociception in mice as determined by the tail-flick test. Intrathecal treatment with 7-benzylidenenaltrexone, a selective delta 1-opioid receptor antagonist, significantly attenuated forced walking stress-induced antinociception. In contrast, intrathecal treatment with naltriben, a selective delta 2-opioid receptor antagonist, had no significant effect on forced walking stress-induced antinociception. Intracerebroventricular treatment with either 7-benzylidenenaltrexone or naltriben had no effect on the forced walking stress-induced antinociception. These results suggest that forced walking stress-induced antinociception is mediated by spinal delta 1-opioid receptors in mice.

Analgesics↗
PubMed1999

[An autopsy case of aortitis resulting in a tear of the aortic valve due to a rupture of the aneurysm of Valsalva's sinus].

A 43-year-old man was admitted to a hospital because of acute dyspnea and nocturnal orthopnea. Echocardiogram and chest CT showed the dilation of thoracic aorta from the root to ascending portion. On the third hospital day, he died suddenly. At autopsy, the cause of death was indicated to be a tear of an aortic valve due to a rupture of the aneurysm of Valsalva's sinus, followed by acute aortic regurgitation and acute cardiac insufficiency. Histopathological findings of thoracic aorta revealed mesoaortitis, characterized by patchy destruction of the media with a moth-eaten appearance of the medial elastic laminae and a microgranuloma formation, a perivascular mononuclear cell infiltration of the vasa vasorum, and a fibrous thickening of the intima and adventitia. However, there were no abnormalities in main branches of aorta and abdominal aorta, and no systemic vasculitis. This case is a rare one in the clinical course, and may be important to be differentiated from other cases with aortitis, especially Takayasu arteritis and syphilitic aortitis.

Acute Disease↗
PubMed1998

Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA-2 in urogenital development.

Mutations resulting in embryonic or early postnatal lethality could mask the activities of any gene in unrelated and temporally distinct developmental pathways. Targeted inactivation of the transcription factor GATA-2 gene leads to mid-gestational death as a consequence of hematopoietic failure. We show here that a 250 kbp GATA-2 yeast artificial chromosome (YAC) is expressed strongly in both the primitive and definitive hematopoietic compartments, while two smaller YACs are not. This largest YAC also rescues hematopoiesis in vitro and in vivo, thereby localizing the hematopoietic regulatory cis element(s) to between 100 and 150 kbp 5' to the GATA-2 structural gene. Introducing the YAC transgene into the GATA-2(-/-) genetic background allows the embryos to complete gestation; however, newborn rescued pups quickly succumb to lethal hydroureternephrosis, and display a complex array of genitourinary abnormalities. These findings reveal that GATA-2 plays equally vital roles in urogenital and hematopoietic development.

Animals↗
PubMed1998

Fatty acid omega and (omega-1)-oxidation within intrasplenically transplanted fetal hepatocytes.

BACKGROUND: The expression and enzymatic activity of the cytochrome P450 LAomega within intrasplenically transplanted hepatocytes was investigated. METHODS: Fetal hepatocytes were harvested from spontaneously hypertensive rats and transplanted into recipient adult spontaneously hypertensive rat spleens. RESULTS: Microscopic examination revealed masses of hepatocytes in the red pulp. Immunochemical studies detected cytochrome P450 LAomega in transplanted hepatocytes by 6 and 10 weeks after transplantation. Cytochrome P450 LAomega mRNA accumulates at 6 weeks after transplantation. Cytochrome P450-arachidonic acid omega/omega-1 hydroxylase activity (formation of 20/19-hydroxyeicosatetraenoic acid) was detected at 10 weeks after transplantation. CONCLUSION: These results demonstrated that fetal hepatocytes grow in the spleen and function similarly to adult hepatocytes.

Animals↗
PubMed1998

Impaired megakaryopoiesis and behavioral defects in mafG-null mutant mice.

The small Maf proteins (MafG, MafK, and MafF), which serve as heterodimeric partner molecules of CNC family proteins for binding in vitro to MARE sites, have been implicated in the regulation of both transcription and chromatin structure, but there is no current evidence that the proteins fulfill these functions in vivo. To elucidate possible contributions of the small Maf proteins to gene regulation, we have ablated the mafG and mafK genes in mice by replacing their entire coding sequences with the Escherichia coli lacZ gene. mafG homozygous mutant animals exhibit impaired platelet formation accompanied by megakaryocyte proliferation, as well as behavioral abnormalities, whereas mafK-null mutant mice are phenotypically normal. Characterization of the mafG and mafK embryonic expression patterns show that their developmental programs are distinct and intersecting, but not entirely overlapping. These results provide direct evidence that the small Maf transcription factors are vital participants in embryonic development and cellular differentiation.

Animals↗
PubMed1998

Thymus requirement and antigen dependency in the "infectious" tolerance pathway in transplant recipients.

We have shown that features of infectious tolerance, as originally described in thymectomized mice, may be applied to euthymic rat recipients of heart transplants. We now report on studies aimed at exposing mechanisms underlying the infectious tolerance pathway, with emphasis on the role of thymus and alloantigen. Pretransplant thymectomy diminished the efficacy of CD4-targeted therapy, with donor-specific tolerance induced in approximately 50% of recipients. Thymus was required for generation of regulatory T cells under the cover of CD4 mAb therapy and for the ability of these cells to confer infectious tolerance. However, thymus was not mandatory to maintain an infectious-permissive environment in cohorts of adoptively transferred recipients. Intragraft expression of IL-2, IL-4, and IL-10 genes was diminished in euthymic and thymectomized tolerant hosts. However, grafts in the latter group showed significant IFN-gamma gene expression, suggesting a less efficient down-regulation of Th1-like cells in the absence of regulatory cells. Indeed, exogenous challenge with rIL-2 or freshly alloactivated spleen cells recreated rejection in thymectomized, but not euthymic, hosts, suggesting that a state of cytokine-responsive anergy contributes to the "noninfectious" form of tolerance in thymectomized rats. The infection-tolerant state did not result from "graft adaptation," and regulatory T cells restricted for the original alloantigen were exposed to its continuous stimulation. The effective memory for suppression was dependent upon persistent donor-specific alloantigen stimulation; it disappeared within 3 weeks after its removal. Hence, both central and peripheral immune mechanisms, orchestrated by the tolerizing alloantigen, contribute to the infectious tolerance pathway in CD4 mAb-treated rat transplant recipients.

Animals↗
PubMed1998

Myb and ets proteins are candidate regulators of c-kit expression in human hematopoietic cells.

Kit is a tyrosine kinase receptor that plays an important role in human hematopoietic cell growth. The promoter elements that modulate the gene's expression have not been extensively studied. Because of c-kit's acknowledged importance in hematopoiesis, we sought to address this issue in more detail. To perform these studies we analyzed a human c-kit 5' flanking fragment approximately 1 kilobase in length. Deletion constructs showed a region approximately 139 nucleotides upstream from the translation initiation site that was critical for promoter activity. A region containing a potential silencing element was also identified. Sequence analysis indicated several potential Myb- and Ets-binding sites. The functional significance of these sites was explored by showing that both wild-type Myb and Ets-2 protein, but not a DNA binding-deficient Myb mutant protein, bound to distinct 5' flanking fragments that included these sites. Furthermore, binding of recombinant Myb and Ets-2 protein to these fragments could be competed with an excess of double stranded oligodeoxynucleotides containing canonical, but not mutated, Myb- or Ets-binding sites. We also showed that the 5' flanking region of c-kit exhibited promoter activity in nonhematopoietic cells only when the cells were transfected with c-myb or ets-2 expression vectors. Moreover, Myb and Ets-2 coexpression in such cells augmented transactivation of c-kit promoter constructs in comparison to that observed in cells transfected with either construct alone. Promoter constructs lacking various Myb and Ets sites deleted were much less effective in this same system. Finally, Myb and Ets-2 mRNA expression was detected in CD34+, Kit low as well as CD34+, Kit bright cells. In aggregate, these data further define the human c-kit promoter's functional anatomy and suggest that Myb and Ets proteins play an important, perhaps cooperative, role in regulating expression of this critical hematopoietic cell receptor.

3T3 Cells↗
PubMed1998

Improvement by FUB 181, a novel histamine H3-receptor antagonist, of learning and memory in the elevated plus-maze test in mice.

Effects of FUB 181 [3-(4-chlorophenyl)propyl-3-(1H-imidazol-4-yl)propyl ether], a novel histamine H3-receptor antagonist, on a scopolamine-induced learning deficit in the elevated plus-maze test were studied in mice. FUB 181 alone (2.5 and 5 mg/kg, i.p.) ameliorated the scopolamine-induced learning deficit in mice. This effect was antagonized by BP 2.94 (10 mg/kg, i.p.), a prodrug of (R)-alpha-methylhistamine (histamine H3-receptor agonist), and by ketotifen (4 mg/kg, i.p.), a histamine H1-receptor antagonist, both penetrating the blood-brain barrier. However, the ameliorating effect of FUB 181 (2.5 mg/kg) was not antagonized by either terfenadine (10 mg/kg, i.p.), a histamine H1-receptor antagonist with poor penetration of the blood-brain barrier, or zolantidine (20 mg/kg, i.p.), a centrally effective histamine H2-receptor antagonist. In a biochemical study, FUB 181 had no significant effect on either acetylcholine or choline level in mice brain at the doses tested. These findings suggest that FUB 181 increases the release of histamine by blocking presynaptic histamine H3 autoreceptors, and that released histamine in turn activates postsynaptic H1 and H2 receptors, predominantly histamine H1 receptors, and in this fashion improves learning and memory in mice. Our findings also suggest that the histaminergic system may play an important role in learning and memory, and that FUB 181 may be a clinical candidate for the therapy of dementia.

Acetylcholine↗
PubMed1998

Double malignant neoplasms occurring long after local radiation to the oral mucosa.

A 59-year-old woman who had received cobalt-60 (60Co) interstitial radiation therapy (total 44 Gy) in the right bucco-gingival region for inflammatory pseudotumour was found to have metachronous double malignant neoplasms. Initial osteosarcoma of the right mandibular angle and subsequent squamous cell carcinoma of the right buccal mucosa were identified 28 and 33 years after the radiation, respectively. Since both tumours were located very close to the focus of previous radiation, the therapy was considered to be responsible for their genesis. The patient had systemic metastases of the osteosarcoma.

Adult↗
PubMed1998

Effects of NIK-247 and tacrine on muscarinic receptor subtypes in rats.

1. The purpose of this study was to compare the effect of NIK-247 on muscarinic receptor subtypes with that of tacrine (THA) in rats. 2. NIK-247 and tacrine dose dependently inhibited the binding of [3H]pirenzepine (M1), [3H]AF-DX 384 (M2), and [3H]4-DAMP (M3). The IC50 values for NIK-247 were 4.4 x 10(-6) M, 1.1 x 10(-5) M, and 1.5 x 10(-5) M, respectively, whereas those for tacrine were 5.8 x 10(-7) M, 2.0 x 10(-6) M, and 5.8 x 10(-6) M, respectively. 3. Gpp[NH]p, a GTP analogue, slightly shifted the curve of displacement of [3H]AF-DX. 384 binding for NIK-247 to the right. However, Gpp[NH]p did not shift the curve of displacement of [3H]pirenzepine and [3H]4-DAMP binding to the right. 4. NIK-247 moderately decreased the rate of beating in right atrial preparations, but did not decrease it below 50% of control level. 5. These findings indicate that NIK-247 is an M1 antagonist, M2 partial agonist, and M3 antagonist.

Aminoquinolines↗
PubMed1998

NIK-247 induces long-term potentiation of synaptic transmission in the CA1 region of rat hippocampal slices through M2 muscarinic receptors.

1. The purpose of this study was to examine whether NIK-247 can, by itself, induce long-lasting changes in synaptic efficacy in the hippocampus. Population spikes evoked by electrical stimulation of the stratum radiatum were recorded in the pyramidal cell layer of the CA1 region of the isolated hippocampus. 2. NIK-247 at 1 x 10(-7) - 1 x 10(-5) M dose dependently increased the amplitude of these spikes. The increase in population spikes by NIK-247 outlasted, for 2 hr, its presence. In addition, the increase in population spikes recovered to 2 hr after washout of NIK-247. Therefore, it was concluded that NIK-247 induced long-term potentiation (LTP) by itself. However, tacrine and physostigmine at 1 x 10(-7) - 1 x 10(-5) M did not increase the amplitude of population spikes and did not induce LTP by themselves. 3. The increase in amplitude of population spikes induced by NIK-247 was completely blocked sensitively by atropine (IC50 = 4.3 x 10(-8)M) but insensitively by pirenzepine (IC50 = 9.1 x 10(-7) M). Carbachol also increased the amplitude of population spikes in the presence of pirenzepine. 4. These findings indicate that the LTP induced by NIK-247 is due to its M2 muscarinic agonistic effect in the CA1 region of the rat hippocampus. It is expected that NIK-247 may be useful for the treatment of Alzheimer disease.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1998

Immunolocalization of aromatase in human minor salivary glands of the lower lip with primary Sjögren's syndrome.

The enzyme aromatase is involved in the conversion of androgens to estrogens and in the modulation of various androgenic and estrogenic actions. Abnormalities of estrogen metabolism have been postulated to play roles in the development and/or pathophysiology of Sjögren's syndrome. In the present study, aromatase was immunolocalized in 75 cases of inflammatory disorders of human minor salivary glands of the lower lip. These included cases of primary Sjögren's syndrome (19 cases), of chronic sialadenitis (34 cases) and of mucous extravasation cysts (22 cases), in order to clarify the possible involvement of in situ estrogen production in primary Sjögren's syndrome. Aromatase immunoreactivity was detected in myoepithelial cells of acini and in interstitial cells adjacent to acini and ducts in 13/19 (68%) cases of primary Sjögren's syndrome. In contrast, aromatase expression was detected in only six of 34 (18%) cases of chronic sialadenitis and in seven of 22 (32%) cases of mucous extravasation cyst. These results suggest that increased aromatase expression in minor salivary glands with primary Sjögren's syndrome in premenopausal women may be involved in the biological features of primary Sjögren's syndrome through the production of estrogens in situ and possibly through the aggravation of the inflammatory reaction.

Adolescent↗