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Biomedical subjects

K Onodera

Publications and source records attributed to K Onodera.

At least 127 records · Page 7Linked to original sources
PubMed1996

Functional correlation of NMDA receptor epsilon subunits expression with the properties of single-channel and synaptic currents in the developing cerebellum.

NMDA receptor (NMDAR) subunits epsilon 1-epsilon 4 are expressed differentially with respect to brain region and ontogenic period, but their functional roles still are unclear. We have compared an epsilon 1 subunit-ablated mutant mouse with the wild-type to characterize the effect of epsilon subunit expression on NMDAR-mediated single-channel currents and synaptic currents of granule cells in cerebellar slices. Single-channel and Western blot analyses indicated that the epsilon 2 subunit disappeared gradually during the first postnatal month in both wild-type and mutant mice. Concomitantly, the voltage-dependent Mg2+ block of NMDAR-mediated EPSCs (NMDA-EPSCs) was decreased. Throughout the developmental period studied, postnatal day 7-24 (P7-P24), the decay time course of NMDA-EPSCs in epsilon 1 mutant (-/-) mice was slower than in wild-type mice. We suggest that the expression of the epsilon 3 subunit late in development is responsible for a reduction in the sensitivity of NMDA-EPSCs to block by extracellular Mg2+ and that receptors containing the epsilon 1 subunit determine the fast kinetics of the NMDA-EPSCs.

Age Distribution↗
PubMed1996

Effect of hepatocyte growth factor on the proliferation of intrasplenically transplanted hepatocytes in rats.

The effect of human hepatocyte growth factor on the proliferation of intrasplenically transplanted hepatocytes was investigated. A human hepatocyte growth factor (360 micrograms/kg BW) was administered intravenously every 24 hr for 5 days following hepatocyte transplantation in rats. A significant increase in hepatocyte proliferation was observed morphologically and immunohistochemically (p < 0.05). The bromodexyuridine labeling index was significantly greater in human hepatocyte growth factor treated rats than in the control rats (p < 0.05). Hepatocyte growth factor may promote the proliferation of intrasplenically transplanted hepatocytes.

Animals↗
PubMed1996

The effects of nondepleting CD4 targeted therapy in presensitized rat recipients of cardiac allografts.

The immunosuppressive effects of RIB-5/2, a nondepleting anti-rat CD4 monoclonal antibody (mAb), were analyzed in a well-defined model of accelerated cardiac allograft rejection. (LEW x BN)F1 hearts are rejected within 24 hours in LEW hosts presensitized with BN skin grafts at day -7. Treatment with RIB-5/2 mAb (3.5 mg/day i.v.) at days -7 and -1, prolonged cardiac allograft survival to the median of >62 days. The long-term recipients rejected acutely third-party (Wistar-Furth) test skin grafts, without an adverse effect on the survival of the original cardiac transplants. Lymphocytes harvested from mAb-treated hosts significantly decreased proliferative responses of donor cells in mixed leukocyte reaction. The cell activation and cytokine elaboration patterns were evaluated at the mRNA and protein levels by competitive template reverse transcriptase polymerase chain reaction and immunohistochemistry, respectively. Cardiac allografts in CD4 mAb-treated rats at 24 hours displayed reduced CD3, CD25, tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-2, interferon (IFN)-gamma, and IL-10 mRNA levels as compared to those in rejecting grafts. Equal amounts of IL-4 mRNA were detected throughout in both animal groups; the expression of IL-10 mRNA increased progressively in the treated hosts. In contrast, IFN-gamma was consistently depressed after mAb therapy. The mRNA levels coding for CD3, CD25, tumor necrosis factor-alpha, IL-1-beta, and IL-2 genes were comparable in long-surviving and rejecting allografts. The staining for IL-2R, IL-2, and IFN-gamma was diminished, whereas the staining for IL-4 was either unaffected or enhanced in well-functioning grafts in RIB-5/2 mAb-treated hosts. The untreated recipients elicited strong circulating IgM allo-Ab response, which peaked around the time of cardiac rejection and then switched to IgG allo-Ab 4-7 days after heart transplantation. Treatment with RIB-5/2 mAb decreased IgM and prevented the switch into the IgG allo-Ab response. In conclusion, the ability of RIB-5/2 mAb treatment to combat accelerated rejection and to produce long-term graft acceptance is unprecedented in our experience in this model. These data provide new insights into the complexities of the cellular and humoral responsiveness, contributing to the the induction of donor-specific unresponsiveness in sensitized hosts. This study, along with our previous reports, indicate that an immune deviation in which intragraft Th1-type cytokines (primarily IFN-gamma) are diminished and Th2-type cytokines (IL-4 and IL-10) are maintained represents the common effector mechanism of CD4 mAb regimens in recipients of vascularized organ allografts.

Animals↗
PubMed1996

A tyrosine kinase-like molecule is localized in the nuclear membrane of neurons: hippocampal behavior under stress.

Protein tyrosine kinases play important roles in the development of the mammalian nervous system during embryogenesis and in the maintenance of function of the adult brain. Using a semi-nested PCR technique based on a short amino acid motif of protein tyrosine kinases, we isolated a human genomic DNA encoding a peptide whose sequence was related to known mammalian protein tyrosine kinases. The expression was examined by Northern blot analysis, and transcripts were detected almost exclusively in the brain. The corresponding cDNA was sequenced, and it was revealed that the gene designated as byk coded for a receptor-like molecule with a motif of protein tyrosine kinase. Immunohistochemical analysis demonstrated that the Byk protein was expressed in neurons and was located in the nuclear envelope. To understand the physiological significance of the Byk protein, we investigated the behavior of this molecule in the hippocampus after ischemia. Byk-like immunoreactivity disappeared from the neurons in the fields CA1 through CA3 and the dentate gyrus of the hippocampus following 20 min of ischemia. After recirculation of blood flow, neurons in the CA3 field and the dentate gyrus re-expressed Byk-like antigen but CA1 neurons did not. Interestingly, Byk-like immunoreactivity was detected in microglial cells and astrocytes in the CA1 field that were activated after ischemia. Byk could be a new tool to study the neuron-glia and glia-glia interactions.

Amino Acid Sequence↗
PubMed1996

Mesodermal- vs. neuronal-specific expression of MafK is elicited by different promoters.

BACKGROUND: Small members of the Maf family of transcriptional regulatory proteins share similar basic-leucine zipper domains but have no intrinsic ability to activate transcription. One member of the family (MafK) has been shown to mediate both negative and positive regulation: in addition to forming a homodimer which represses transcription, MafK can also form a heterodimer with p45 (the large subunit of erythroid transcription factor NF-E2) to activate transcription. RESULTS: We examined the expression of mafK during murine development. mafK mRNA was first detected in 7.5 days post coitus (dpc) embryonic mesoderm and persisted in mesodermal derivatives (mesenchymal and haematopoietic cells) thereafter. However, around 13 dpc mafK was also strongly induced in neuronal cells and it is broadly expressed in neurones in postnatal mouse. The neuronal expression of mafK is directed by a distinct promoter located 6 kbp 3' to the mesoderm-specific promoter. mafK in neurones associates with a different partner molecule from p45. In transgenic mice, a regulatory domain in the immediate vicinity of the mesodermal promoter was found to direct mesenchymal, but not haematopoietic, expression of mafK. CONCLUSION: The cell type- and developmental stage-specific expression of MafK suggests that, in addition to its demonstrated role in erythroid transcriptional regulation, MafK also plays an important regulatory role in other mesodermally and neuroectodermally derived tissues during mouse embryonic development.

Animals↗
PubMed1996

A new technique for laparoscopic cholecystectomy--retrograde laparoscopic cholecystectomy: an analysis of 81 cases.

BACKGROUND AND STUDY AIMS: A new technique of laparoscopic cholecystectomy is presented here. This new method, retrograde laparoscopic cholecystectomy (RLC) from fundus to cystic duct downward, may have advantages when exposure of the cystic duct and the common duct are difficult and therefore hazardous. PATIENTS AND METHODS: We carried out laparoscopic cholecystectomy in 173 patients; RLC was performed in 81, The operative procedure is as follows: first, the cystic duct and artery are exposed at the junction of the ampulla. The cystic duct is clipped, and the artery is divided. Removal of the gallbladder is then started from the fundus to cystic duct downward. After the gallbladder has been dissected from the liver bed, the cystic duct is double-clipped and divided. This approach provides better visualization of the gallbladder, cystic duct, and common duct, with less chance of common duct injury, due to clear identification of the ductal system, without the need for intraoperative cholangiography. RESULTS: Eighty-one RLCs were performed without severe complications, either immediate or late. The mean operating time was 23 minutes shorter in RLC than in the usual laparoscopic cholecystectomy, because intraoperative cholangiography was used much less often. CONCLUSION: RLC appears to be a safe procedure, and does not affect the conventional method.

Adult↗
PubMed1996

Chemical characterization of peroxidized low-density lipoprotein in plasma and aortic atheroma.

Hydroperoxidized cholesteryl linoleate (HPO-CL, spot X1) was produced by peroxidation of normal LDL isolated from plasma of healthy persons. Spot X stained on thin-layer chromatography plate (silica 60) between triglycerides and free fatty acids. The solvent mixture used consisted of petroleum ether 75, ethyl ether 25, and acetic acid 1. Spot X1 of plasma from healthy subjects stained slightly. It was also identified in plasma LDL of patients with atherosclerotic diseases, and in total lipids extracted from aortic atheroma obtained at autopsy. Whereas spot X1 obtained from plasma LDL of patients with atherosclerotic diseases consisted of HPO-CL, spot X1 obtained from aortic atheroma was reduced HPO-CL (hydroxide CL). Spot X1 of obtained from aortic atheroma was reduced HPO-CL (hydroxide CL). Spot X1 of aortic atheroma did not react to p-methoxydiphenylpyrenylphosphine (MP3)-an agent which shows only positive reaction to hydroperoxide chemical structures-although spot X1 of plasma LDL from atherosclerotic diseases reacted positively to MP3. Moreover, spot X1 obtained from aortic atheroma showed the same Rf value as that of the reduced HPO-CL. The IR profile of spot X1 obtained from aortic atheroma was similar to that of hydroxide CL, although the IR profiled HPO-CL was similar to that obtained from plasma LDL of atherosclerotic patients. In addition, HPO-CL was not recognized in the LDL fraction with clathrin-coated pits from aortic atheroma.

Adult↗
PubMed1996

Peroxidized low-density lipoprotein with four kinds of hydroperoxidized cholesteryl linoleate estimated in plasma of young heavy smokers.

AIM: To clarify the mechanisms of vascular complications due to heavy smoking, it was studied whether hydroperoxidized low-density lipoprotein (HPO-LDL) was estimated in plasma of young heavy smokers. METHOD: Plasmas were separated from 15 young male students (HS-M) who smoked more than 30 cigarettes/day over 5 years, and from 10 nonsmoker students (NS-M) too. LDL was isolated by ultracentrifugation. HPO-cholesteryl linoleate (HPO-CL) was identified by thin-layer chromatography (TLC), and lipid peroxide was measured by Determiner LPO (Kyowa Medics Co., Ltd, Tokyo, Japan). The molecular structure of lipid peroxide in LDL was identified using GMS analysis, HPLC chromatography and 1H-NMR analysis. RESULTS: (1) HPO-CL was clearly observed on the TLC in LDL lipids of HS-M but from NS-M it was barely found. (2) Lipid peroxide in LDL separated from HS-M consisted of HPO-CL and reduced HPO-CL. CONCLUSION: Peroxidized LDL was estimated in plasma with young heavy smokers. Because of injurious reactions in vessels of peroxidized LDL, it is considered that heavy smoking is one of the risk factors for vascular complications in heavy smokers.

Adult↗
PubMed1996

Batroxobin accelerates lipid accumulation of peroxidized low density lipoprotein in mouse peritoneal macrophages.

Mouse peritoneal macrophages were incubated in DMEM medium with batroxobin (DF-521) to determine the effect of batroxobin on the internalization of peroxidized low-density lipoprotein (pox-LDL) by transmission electron microscopy. Although the morphology of the mouse peritoneal macrophages after incubation with DMEM, normal LDL (n-LDL) and n-LDL plus batroxobin was similar to that of the cells before incubation, they exhibited numerous cytoplasmic lipid droplets after incubation with pox-LDL for 4 h. After addition of batroxobin to the medium containing pox-LDL, the production of lipid droplets in the mouse peritoneal macrophages was tremendously accelerated. Batroxobin accelerates the phagocytosis and degradation of pox-LDL by macrophages.

Animals↗
PubMed1996

Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone.

An autopsy case of ACTH-producing thymic carcinoid with Cushing's syndrome is reported. The patient was a 63-yr-old man with multiple bone metastases from an undetermined primary site. Hyperpigmentation was observed at the terminal stage. The plasma levels of ACTH, cortisol, chromogranin A, and urinary 17-hydroxy-corticosteroids were extremely high, and ectopic ACTH-producing neuroendocrine tumor was diagnosed. In addition, plasma CRH was high. Autopsy revealed that the patient had primary thymic carcinoid with extensive metastases. Remarkable hyperplasia of the adrenal cortexes and Crooke's hyaline degeneration of the pituitary gland were consistent with Cushing's syndrome by ectopic ACTH production. There were multiple CRH-producing cells without degenerative changes in the hypothalamus. The tumor cells were immunoreactive to ACTH, CRH, and the cleavage enzyme PC2. POMC messenger ribonucleic acid and PC2 messenger ribonucleic acid were detected in the tumor cells by an in situ hybridization method. Expression of PC2 was considered to induce hyperpigmentation by producing alpha MSH. Despite hypercortisolism and ectopic production of CRH by the tumor cells, hypothalamic CRH cells were not atrophic. This case is a good example to demonstrate the correlation between CRH and the hypothalamo-pituitary-adrenal axis as well as hyperpigmentation in Cushing's syndrome.

Adrenocorticotropic Hormone↗
PubMed1996

Effect of inferior vena cava occlusion on left ventricular end-systolic pressure-volume relations in intact canine hearts--modulation by the autonomic nervous system.

The effect of inferior vena cava occlusion (IVCO) on end-systolic pressure-volume relations (ESPVR) of the left ventricle was studied in intact canine hearts. In 12 anesthetized open-chest dogs, left ventricular (LV) pressure and volume were measured simultaneously using a microtip catheter and a conductance catheter, respectively. ESPVR was constructed from LV pressure-volume loops during IVCO (10 sec) and subsequent IVCO release under 5 conditions: control, after righ or left cardiac sympathetic nerve (CSN) stimulation, bilateral vagotomy (VAT), and both VAT and bilateral CSN resection. Emax in IVCO release was significantly greater than that in IVCO in the control state. Following right or left CSN stimulation, Emax was increased increased in both IVCO and IVCO release, with the same hysteretic change in Emax. With VAT, however, no hysteretic change was observed because Emax was the same in IVCO and IVCO release. After VAT and CSN resection, Emax was decreased in both IVCO and IVCO release, and again no hysteretic change was observed. These data imply that a sudden decrease in venous return into the heart induces a decrease in afferent vagal nerve activity, and thus increases efferent CSN activity, resulting in enhanced myocardial contractility.

Animals↗
PubMed1996

Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

In the process of screening for squalene synthase inhibitors from microbial fermentation products we have isolated a novel compound, named schizostatin (Fig. 1), from the culture broth of the mushroom, Schizophyllum commune SANK 17785. Schizostatin inhibited rat liver microsomal squalene synthase dose dependently and the IC50 value was 0.84 microM. The inhibition was competitive with respect to farnesylpyrophosphate with a Ki value of 0.45 microM.

Alkyl and Aryl Transferases↗
PubMed1996

Schizostatin, a novel squalene synthase inhibitor produced by the mushroom, Schizophyllum commune. II. Structure elucidation and total synthesis.

Schizostatin (1) has been isolated as a potent and selective inhibitor of squalene synthase. Its structure has been determined using spectroscopic methods: the compound is shown to be a diterpenoid which has a trans-dicarboxylic acid moiety. Total synthesis of schizostatin (1) was achieved by the highly regio- and stereoselective coupling reaction of an allylic bromide with a barium reagent. The Z-isomer 16 was also prepared using the stereoselective syn-addition of an organocopper reagent to acetylenedicarboxylate.

Enzyme Inhibitors↗
PubMed1996

[Retroperitoneal fibrosis with involvement up to the mediastinal space].

A 60-year-old man presented with sudden palpitations in September 1993, and was admitted to hospital with a diagnosis of atrial fibrillation and heart failure. The patient was suspected of having collagen disease, because of a positive test for antinuclear antibodies and a high sedimentation rate. He was referred to lou hospital. Chest radiographic findings were suggestive of cardiomegaly and cardiac murmurs were audible, which indicated the presence of heart disease. A chest Ct scan revealed a lesion surrounding the intramediastinal large vessels and the heart from the level of the confluence of the left brachiocephalic vein and the superior vena cava. Suspicion of a mediastinal tumor led the patient to be admitted to the respiratory department. Percutaneous needle biopsy with a Trucut needle revealed non-specific chronic inflammation. An abdominal CT scan showed that the lesion surrounding the descending aorta traversed the diaphragm, reached the renal pelvis along both renal arteries, and caused narrowing of the ureter and left hydronephrosis. Based on these findings, retroperitoneal fibrosis was diagnosed. Treatment with steroids caused the lesion to shrink.

Anti-Inflammatory Agents↗
PubMed1996

[The changes of blood gas analysis values and platelet aggregability on acute phase in the experimental model of pulmonary embolism prepared by sephadex G-75 (SG-75) injection].

To study pathophysiologic phenomena in acute pulmonary embolism, we injected sephadex G-75 (SG-75) into rabbit auricular veins and measured the changes in blood gases and in platelet aggregability. Severe hypoxemia developed within 10 minutes of SG-75 injection. Microscopic examination of samples taken 120 minutes after SG-75 injection pulmonary artery had been embolized by the SG-75 particles, and that thrombin had formed around the particles. The lowest platelet counts were measured 10 minutes after SG-75 injection. The rates of platelet aggregation induced by adenosine diphosphate and by platelet-activating factor were abnormally low until 40 minutes after SG-75 injection. These results suggest that platelets were activated by anoxia and that the activated platelets moved around the emboli after obstruction of the pulmonary artery. We conclude that decreases in PaO2 and changes in platelet aggregability exacerbate the pathophysiologic processes in acute pulmonary embolism.

Acute-Phase Reaction↗
PubMed1996

Sodium ionophore converts growth manner of vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVES: Vasoconstrictor peptides such as endothelin (ET) cause hypertrophy of vascular smooth muscle cells (VSMC) in Wistar Kyoto rats (WKY) and hyperplasia in spontaneously hypertensive rats (SHR). They also induce an increase in Na+ concentration ([Na+]i) and activate protein kinase C (PKC) independently. Therefore, we tested the hypothesis that the increase in [Na+]i may be involved in the conversion of growth manner under activated PKC in SHR VSMC. METHODS AND RESULTS: 10(-7) M phorbol ester (TPA) increased the diameter and protein content of VSMC from both strains under 18% serum conditions. Further addition of 10(-6) M gramicidin (Na+ ionophore) converted TPA-induced hypertrophy to hyperplasia, which was due to the quick transition from S to G2/M phase, only in SHR VSMC. Western blot analysis showed that serum- and TPA-induced tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was potentiated by 10(-6) M gramicidin in SHR. [Na+]i, which was measured by sodium-binding benzofuran isophthalate (SBFI), was increased about 35 mM by 10(-6) M gramicidin in both strains, but TPA did not affect basal [Na+]i and the gramicidin-induced increase in [Na+]i. CONCLUSIONS: We conclude that sodium ionophore may convert hypertrophy to hyperplasia synergistically with activated PKC in SHR VSMC, possibly by MAP kinase phosphorylation.

Animals↗