Biomedical subjects

K Ohashi

Publications and source records attributed to K Ohashi.

At least 127 records · Page 7Linked to original sources

PubMed2000

A low dose of lithium chloride selectively induces Fos protein in the central nucleus of the amygdala of rat brain.

1. Lithium is a very effective treatment for mood disorders. To elucidate the neural substrates of the mood stabilizing actions of lithium, in the present study the authors investigated the effects of a low dose of lithium on regional expression of Fos protein. 2. The administrations of a high dose of lithium chloride (100 mg/kg) induced Fos in widespread areas of the rat brain. In contrast, administration of a low dose of lithium chloride, equivalent to a therapeutic dose in humans, induced Fos only in the central nucleus of the amygdala. 3. These results demonstrate that the central nucleus of the amygdala plays important role in the neural framework that is responsible for the mood-stabilizing effect of lithium.

Amygdala↗

PubMed2000

Antigenic differences in the H proteins of canine distemper viruses.

Antigenic properties between new Japanese field isolates and vaccine strains of canine distemper virus (CDV) have been compared using four monoclonal antibodies (MAbs) (JD-5, JD-7, JD-11 and d-7) against the hemagglutinin (H) proteins of CDV. JD-5, JD-7 and JD-11 are newly established antibodies. Three MAbs, namely d-7, JD-5 and JD-11, reacted similarly to all the CDV strains examined. However, JD-7 reacted much more strongly with the vaccine strains and an old field isolate than the recent field isolates in immunofluorescence, radio immunoprecipitation and virus neutralization assays. These results indicate that an antigenic region in the H protein, concerned with neutralization and recognized by JD-7, has been altered in the recent field isolates.

Animals↗

PubMed2000

Clozapine- and olanzapine-induced Fos expression in the rat medial prefrontal cortex is mediated by beta-adrenoceptors.

The atypical neuroleptics, clozapine and olanzapine, have superior therapeutic efficacy against the negative symptoms of schizophrenia, compared with the typical neuroleptics. Recently, it has been suggested that the ability of clozapine and olanzapine to induce Fos expression in the medial prefrontal cortex (mPFC), contribute to their therapeutic efficacy. However, the mechanisms underlying the neuropharmacological effects of clozapine and olanzapine in the mPFC remain elusive. In the present study, we demonstrate that clozapine- and olanzapine-induced Fos expression in the mPFC are inhibited by propranolol. We also show that clozapine and olanzapine induce Fos expression in the locus coeruleus. These results suggest that clozapine and olanzapine increase noradrenaline release by stimulating noradrenergic neuronal activity in the locus coeruleus and, consequently, increased noradrenaline induce Fos expression in the mPFC via beta-adrenergic receptors. This postulated sequence may be one of mechanisms by which clozapine-like atypical neuroleptics are more effective for the negative symptoms of schizophrenia.

Adrenergic beta-Antagonists↗

PubMed2000

Carbamazepine suppresses methamphetamine-induced Fos expression in a regionally specific manner in the rat brain. Possible neural substrates responsible for antimanic effects of mood stabilizers.

Carbamazepine (CBZ) has been widely used for treatment of manic states. Because amphetamine produces effects in humans similar to those of idiopathic mania, acute methamphetamine administration could serve as a model of this condition. To elucidate the neurobiological substrates responsible for the antimanic effects of carbamazepine, this study investigated the effects of chronic carbamazepine administration on regional Fos protein expression induced by a single dose of methamphetamine (2mg/kg). Chronic treatment with CBZ (0.25% in food for 7 days, followed by 0.5% for 7 days; final mean serum carbamazepine concentration: 4.09 +/- 0.34 microg/ml) significantly attenuated the number of Fos-like immunoreactivity-positive nuclei induced by methamphetamine administration in the core of the nucleus accumbens and the caudate/putamen. The results indicate these brain regions are involved in the antimanic effects of carbamazepine.

Amphetamine-Related Disorders↗

PubMed2000

A critical role for a Rho-associated kinase, p160ROCK, in determining axon outgrowth in mammalian CNS neurons.

We tested the contribution of the small GTPase Rho and its downstream target p160ROCK during the early stages of axon formation in cultured cerebellar granule neurons. p160ROCK inhibition, presumably by reducing the stability of the cortical actin network, triggered immediate outgrowth of membrane ruffles and filopodia, followed by the generation of initial growth cone-ike membrane domains from which axonal processes arose. Furthermore, a potentiation in both the size and the motility of growth cones was evident, though the overall axon elongation rate remained stable. Conversely, overexpression of dominant active forms of Rho or ROCK was suggested to prevent initiation of axon outgrowth. Taken together, our data indicate a novel role for the Rho/ROCK pathway as a gate critical for the initiation of axon outgrowth and the control of growth cone dynamics.

Actins↗

PubMed2000

Cyclin D1 expression is useful as a prognostic indicator for advanced esophageal carcinomas, but not for superficial tumors.

The purpose of the present study was to define the overexpression of cyclin D1 in superficial and advanced esophageal carcinomas and to investigate whether the expression of this molecule indicates a poor prognosis. This study included 41 patients with superficial esophageal carcinomas (Tis and T1) and 48 patients with advanced esophageal carcinomas (T2, T3, and T4). The expression of cyclin D1 in surgically resected specimens was evaluated immunohistochemically with a monoclonal antibody. Positive immunoreactivity was found in 31 of 89 cases (35%). Overexpression of cyclin D1 did not correlate with TNM classification or histologic type. Of the 48 patients with advanced esophageal carcinomas, 32 patients with cyclin D1-negative tumors survived longer than did 16 patients with cyclin D1-positive tumors (P = 0.0017). In contrast, we observed no survival difference between patients with cyclin D1-positive and -negative superficial esophageal carcinoma. These results suggest that cyclin D1 indicates a poor prognosis in cases of advanced esophageal carcinoma but not in cases of superficial esophageal carcinoma.

Biomarkers, Tumor↗

PubMed2000

Medical markup language (MML) for XML-based hospital information interchange.

Medical Markup Language (MML) has been developed over the last 6 years in order to create a set of standards by which medical data, within Japan and hopefully worldwide, can be stored, accessed and exchanged in any number of physical locates. The MML version 2.21 is characterized by XML as meta-language, module structure for each document and enhancement of linking function among documents. Data exchange specification has been also added for query and reply. MML instances are composed of MML header and MML body. The MML header includes information for data transmission, while MML body includes several module items. One module item contains two elements: document information and module content. Nine MML module contents are defined at the present time: patient information, health insurance information, diagnosis information, lifestyle information, basic clinic information, particular information at the time of first visit, progress course information, surgery record information and clinical summary information.

Clinical Laboratory Techniques↗

PubMed2000

Efficient lentiviral transduction of liver requires cell cycling in vivo.

Human-immunodeficiency-virus (HIV)-based lentiviral vectors are a promising tool for in vivo gene therapy. Unlike Moloney-murine-leukaemia-based retroviruses (MLV), lentiviruses are believed to stably transduce quiescent (non-cycling) cells in various organs. No previous studies, however, have directly established the cell-cycle status of any transduced cell type at the time of vector administration in vivo. In vitro studies using wild-type HIV or HIV-based vectors have shown that, in some cases, cell-cycle activation is required for infection, even though cellular mitosis is not an absolute requirement for integration. Even if the block in reverse transcription is overcome in quiescent T cells, productive infection by HIV cannot be rescued in the absence of cell-cycle activation. The potential use of these vectors for gene therapy prompted our study, which establishes a cell-cycle requirement for efficient transduction of hepatocytes in vivo.

Animals↗

PubMed2000

Sustained survival of human hepatocytes in mice: A model for in vivo infection with human hepatitis B and hepatitis delta viruses.

Persistence of hepatocytes transplanted into the same or related species has been established. The long-term engraftment of human hepatocytes into rodents would be useful for the study of human viral hepatitis, where it might allow the species, technical and size limitations of the current animal models to be overcome. Although transgenic mice expressing the hepatitis B virus (HBV) genome produce infectious virus in their serum, the viral life cycle is not complete, in that the early stages of viral binding and entry into hepatocytes and production of an episomal transcriptional DNA template do not occur. As for hepatitis delta virus (HDV), another cause of liver disease, no effective therapy exists to eradicate infection, and it remains resistant even to recent regimens that have considerably changed the treatment of HBV (ref. 13). Here, we demonstrate long-term engraftment of primary human hepatocytes transplanted in a matrix under the kidney capsule of mice with administration of an agonistic antibody against c-Met. These mice were susceptible to HBV infection and completion of the viral life cycle. In addition, we demonstrate super-infection of the HBV-infected mice with HDV. Our results describe a new xenotransplant model that allows study of multiple aspects of human hepatitis viral infections, and may enhance studies of human liver diseases.

Animals↗

PubMed2000

Cure of refractory duodenal ulcer and infection caused by Helicobacter pylori by high doses of omeprazole and amoxicillin in a homozygous CYP2C19 extensive metabolizer patient.

A 53-year old female patient with duodenal ulcer and Helicobacter pylori infection was treated three times with a proton pump inhibitor-based triple therapy, such as lansoprazole-clarithromycin-amoxicillin (INN, amoxicilline) and lansoprazole-minocycline-cefaclor. However, the H pylori infection was not cured. A culture test revealed that her infection was a clarithromycin-resistant but amoxicillin-sensitive strain of H pylori. Moreover, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis revealed that she was a homozygous extensive metabolizer of cytochrome P450 (CYP) 2C19 (wt/wt). The usual dose of the proton pump inhibitor was therefore assumed to be insufficient for her and then she was treated with a high dose of omeprazole (120 mg/day) and amoxicillin (2,250 mg/day) for 2 weeks. The H pylori infection and the ulcer lesion were then cured. One of the factors associated with success or failure of cure of H pylori infection by the proton pump inhibitor-based triple therapy appeared to be CYP2C19 genotype status. Dual treatment with a sufficient dose of a proton pump inhibitor plus amoxicillin could cure H pylori infection even after the failure to cure H pylori infection by a usual proton pump inhibitor-based triple therapy in patients with the wt/wt homozygous extensive metabolizer genotype of CYP2C19.

Amoxicillin↗

PubMed2000

Promotion of the uptake of PS liposomes and apoptotic cells by a product of growth arrest-specific gene, gas6.

Gas6, a ligand of receptor tyrosine kinases Axl, Sky, and Mer, potentiates cell proliferation and prevents cell death. It also contains g-carboxylglutamic acid residues that mediate the interaction of some blood coagulation factors with negatively charged phospholipids. In our previous study, we demonstrated that Gas6 specifically binds to phosphatidylserine (PS) and links Axl-expressing cells to the PS-coated surface. In this study, to further understand the biological role of the interaction of Gas6 with PS, we examined the effect of Gas6 on the uptake of PS liposomes by macrophages. In vitro phagocytosis studies showed that Gas6 enhanced the uptake of PS liposomes approximately threefold and that the interaction of Gas6 with the surface of macrophages was essential for this enhancement. Analyses of the mechanism of the uptake of PS liposome suggested that Gas6 interacts with PS liposome via its N-terminal Gla domain and with macrophages via its C-terminal domain. Like that of PS liposomes, the uptake of apoptotic cells by macrophages was also enhanced, approximately twofold, in the presence of Gas6. These findings suggest that Gas6 may help phagocytic cells recognize cells with PS exposed on their surfaces, which is considered to be one of the mechanisms for clearing away dying cells. Thus, Gas6 may play a critical role in homeostasis by facilitating the clearance of PS-expressing cells.

Animals↗

PubMed2000

Inhibitory effect of insulin on bradykinin-induced venodilation.

BACKGROUND: Excessive insulin is one of the risk factors of hypertension and arteriosclerosis despite its vasodilative properties shown in recent studies. Although many vasoactive substances contribute and interact with each other in the development of hypertension, the interactions between insulin and other vasoactive substances have yet to be elucidated. OBJECTIVE: To assess the effect of insulin on the action of bradykinin. METHODS: The vasodilating effect of bradykinin was evaluated, with or without coadministration of insulin, in human dorsal hand veins of healthy volunteers. In cultured porcine aortic endothelial cells, the bradykinin-induced increase of intracellular calcium was also investigated before and after insulin administration. RESULTS: Insulin significantly attenuated bradykinin-induced increase in intracellular calcium and venodilation in cultured endothelial cells and human dorsal hand veins, respectively. CONCLUSIONS: These findings suggest that insulin attenuates the bradykinin-induced calcium elevation in endothelial cells and may decrease the production of vasodilative substances from endothelial cells, resulting in the reduction of vasodilation. This effect may contribute to the development of hypertension in patients with hyperinsulinaemia.

Adult↗

PubMed2000

Autocrine interferon-beta stimulation augments nitric oxide production by mouse macrophage J774A.1 cells infected with herpes simplex virus type 1.

The pathogenic roles of nitric oxide (NO) in mouse models have been reported for herpes simplex virus type 1 (HSV-1)-induced pneumonia as well as endotoxin shock. We compared the mechanism of NO production induced by HSV-1 with that induced by lipopolysaccharide (LPS) using a mouse macrophage cell line, J774A.1. Both HSV-1 and LPS induced NO production as well as antiviral activity, which were attenuated by anti-interferon (IFN)-beta treatment. These results suggest that autocrine IFN-beta plays a role in NO release by J774A.1 cells stimulated with HSV-1 or LPS.

Animals↗

PubMed2000

Helicobacter pylori and the t(11;18)(q21;q21) translocation in gastric low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type.

The reported regression of mucosa-associated lymphoid tissue (MALT) type gastric low-grade B-cell lymphoma following treatment for Helicobacter pylori (H. pylori) infection has not yet been comprehensively analyzed, especially in relation to the recently identified c-IAP2-MALT1 / MLT gene alteration resulting from the t(11;18)(q21;q21) chromosomal translocation found in MALT lymphoma. The relationship between MALT lymphomas and H. pylori was investigated in 30 patients who received an antibacterial treatment. Patients were followed up by means of endoscopy and biopsy. Molecular genetic analyses focused on the presence or absence of the immunoglobulin heavy chain (IgH) gene and / or MALT1 / MLT gene alteration resulting from t(11;18)(q21;q21) translocation. H. pylori was positive in 26 of the 30 patients. The overall success rate of cure of H. pylori infection was 96% (25 / 26). Thirteen patients (52%) showed complete remission (CR) of lymphoma, nine (36%) partial remission (PR), and three (12%) registered no change (NC). Statistical analysis revealed significant differences between CR and PR / NC patients in age ( < 60 or 60), in lymphoma location (single or multiple sites) and in the presence or absence of gene rearrangement before eradication (P < 0.05). Endoscopy showed a cobblestone appearance only in PR cases and polypoid features predominantly in NC cases. Two NC patients with polypoid gross appearance showed rearrangements involving either c-IAP2 or MALT1 gene in Southern blot analysis, while none of seven other resected patients with non-polypoid superficial gross appearance showed rearrangement. Gastric MALT lymphoma could be pragmatically subdivided into three groups, CR (MALT-A), PR (MALT-B), and NC (MALT-C) on the basis of the reaction to eradication of H. pylori. We speculate that MALT-A may represent an incipient neoplasm or dysplasia, MALT-B a neoplasm activated by antigenic stimulation of H. pylori, and MALT-C a lymphoma independent of H. pylori. Polypoid lesions in MALT-C were associated with c-IAP2-MALT1 / MLT gene alteration resulting from t(11;18)(q21;q21). This classification is thought to be clinically significant for deciding the most appropriate mode of treatment of MALT-type lymphoproliferative disorders.

Adult↗

PubMed2000

No association of the 5' promoter region polymorphism of CYP17 with breast cancer risk in Japan.

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5' promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5 - 50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58 - 1.64) for TC-genotype and 0.81 (0.39 - 1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother / sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5' promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.

Adult↗

PubMed2000

Temporal contribution of body movement to very long-term heart rate variability in humans.

A newly developed, very long-term ( approximately 7 days) ambulatory monitoring system for assessing beat-to-beat heart rate variability (HRV) and body movements (BM) was used to study the mechanism(s) responsible for the long-period oscillation in human HRV. Data continuously collected from five healthy subjects were analyzed by 1) standard auto- and cross-spectral techniques, 2) a cross-Wigner distribution (WD; a time-frequency analysis) between BM and HRV for 10-s averaged data, and 3) coarse-graining spectral analysis for 600 successive cardiac cycles. The results showed 1) a clear circadian rhythm in HRV and BM, 2) a 1/f (beta)-type spectrum in HRV and BM at ultradian frequencies, and 3) coherent relationships between BM and HRV only at specific ultradian as well as circadian frequencies, indicated by significant (P < 0.05) levels of the squared coherence and temporal localizations of the covariance between BM and HRV in the cross-WD. In a single subject, an instance in which the behavioral (mean BM) and autonomic [HRV power >0.15 Hz and mean heart rate (HR)] rhythmicities were dissociated occurred when the individual had an irregular daily life. It was concluded that the long-term HRV in normal humans contained persistent oscillations synchronized with those of BM at ultradian frequencies but could not be explained exclusively by activity levels of the subjects.

Adult↗

PubMed2000

Improvement in the histopathology of hearts from cardiomyopathic BIO TO-2 hamsters following long-term administration of amlodipine and cilnidipine.

The effect of long-term administration of amlodipine and cilnidipine was examined on the histopathology and 1,4-dihydropyridine (DHP) calcium channel antagonist receptors in the left ventricle of BIO TO-2 hamsters, a model of dilated cardiomyopathy (DCM). Oral administration of amlodipine (3 and 10 mg/kg/d, 19 weeks) in 7 week-old BIO TO-2 hamsters produced a significant reduction in calcium deposition and necrosis with little change in the cavity area and fibrosis. A reduction of calcium deposition and necrosis in the myocardium of BIO TO-2 hamsters was also seen following similar administration of cilnidipine (10 mg/kg/d). The long-term administration of amlodipine (3 and 10 mg/kg/d) caused a significant increase (36.6 and 21.7%, respectively) in the Bmax for specific (+)-[3H]PN 200-110 binding in the myocardium from BIO TO-2 hamsters, compared with that in control hamsters. In conclusion, the present study has shown that long-term administration of amlodipine and cilnidipine improves calcium deposition and necrosis in the myocardium from BIO TO-2 hamsters. Thus, these data suggest that both agents may be effective pharmacological treatments of DCM.

Amlodipine↗

PubMed2000

Indonesian medicinal plants. XXIII. Chemical structures of two new migrated pimarane-type diterpenes, neoorthosiphols A and B, and suppressive effects on rat thoracic aorta of chemical constituents isolated from the leaves of Orthosiphon aristatus (Lamiaceae).

Two novel migrated pimarane-type diterpenes named neoorthosiphols A (1) and B (2) were isolated from the water decoction of the leaves of Orthosiphon aristatus (Lamiaceae), which has been prescribed in Javanese traditional medicine (jamu) for the treatment of hypertension, etc. The absolute chemical structures have been elucidated on the basis of physicochemical properties. It has been found that two migrated pimarane-type diterpenes (1, 2), four isopimarane-type diterpenes (3, 4, 5, 6), three benzochromenes (7, 8, 9) and two flavones (12, 13) exhibit a suppressive effect on contractile responses in rat thoracic aorta, among thirteen chemical constituents (1-13) isolated from the leaves.

Animals↗