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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 793 records · Page 44Linked to original sources
PubMed1995

Establishment of canine pulmonary hypertension with dehydromonocrotaline. Importance of larger animal model for lung transplantation.

Single lung isografting in rats with pulmonary hypertension has been reported. However, it is hard to evaluate cardiopulmonary hemodynamics accurately or to use circulatory assists during procedures using rats. Therefore, we tried to establish a model of pulmonary hypertension in the beagle. Twenty young beagles were randomized into 3 groups. An injection of dehydromonocrotaline of 1.5 mg/kg (group 1, n = 7), 3.0 mg/kg (group 2, n = 10), or 4.5 mg/kg (group 3, n = 3) was performed via the right atrium. Two dogs in group 2 and all the dogs in group 3 died of acute pulmonary edema. During the 8 weeks after injection, the systolic pulmonary arterial pressure and pulmonary vascular resistance index increased significantly in group 2 from 21 +/- 2 to 56 +/- 9 mmHg and from 106 +/- 39 to 826 +/- 176 dynes.sec.cm-5.m2, respectively (P < 0.01). The changes in group 1 were less pronounced. The dogs in group 2 also had a rise in their plasma endothelin-1. Pathologic analysis revealed thickening of the media in small pulmonary arteries and hypertrophy of the right ventricular myocardium. Our data indicate that beagles treated with 3.0 mg/kg dehydromonocrotaline produced a unique, relatively noninvasive model of pulmonary hypertension. In the model, right ventricular failure prevented us from clamping one pulmonary artery. These relatively large animals with pulmonary hypertension will be valuable for further studies of lung transplantation.

Animals↗
PubMed1995

Vitamin B6 modulates expression of albumin gene by inactivating tissue-specific DNA-binding protein in rat liver.

The level of albumin mRNA in the liver of vitamin B6-deficient rats was found to be 7-fold higher than that of control rats. Since the transcriptional activity of the albumin gene, as measured by a nuclear run-on assay, was increased 5-fold in vitamin B6 deficiency, the higher concentration of albumin mRNA in the liver of vitamin-deficient rats could be attributed to the enhanced rate of transcription. The promoter proximal sequences of the albumin gene interact with a number of tissue-specific transcription factors including HNF-1 and C/EBP. We determined the binding activities of liver nuclear extracts to the HNF-1- and C/EBP-binding sites by gel mobility-shift assay and found that the activities of the extract prepared from liver of vitamin B6-deficient rats were greater than those of controls. As the concentrations of C/EBP in nuclear extracts from control and vitamin-deficient rats, estimated by Western-blot analysis, were essentially the same, the lower binding activity of the extract from control liver is probably due to inactivation of tissue-specific factors by pyridoxal phosphate and/or its analogues. We therefore examined the effect of pyridoxal phosphate and its analogues on the binding activity of nuclear extract in vitro and found that only pyridoxal phosphate effectively inhibited the binding. These observations indicate that vitamin B6 modulates albumin gene expression through a novel mechanism that involves inactivation of tissue-specific transcription factors by direct interaction with pyridoxal phosphate.

Albumins↗
PubMed1995

Role of endothelin-1 in beagles with dehydromonocrotaline-induced pulmonary hypertension.

BACKGROUND: Although plasma levels of endothelin-1 (ET-1) increase in patients with pulmonary hypertension (PH), its role in PH is unknown. We investigated the contribution of endogenous ET-1 to cardiopulmonary changes in beagles with dehydromonocrotaline (DMCT)-induced PH. METHODS AND RESULTS: Eight 3-month-old beagles were given a single injection of 3 mg/kg DMCT via the right atrium. During the 8 weeks after injection, the mean pulmonary arterial pressure (PAP) and plasma ET-1 level increased significantly from 11.6 +/- 2.3 to 35.9 +/- 7.1 mm Hg and from 1.24 +/- 0.25 to 3.25 +/- 0.94 pg/mL, respectively. In controls, ET-1 infusion elevated the systemic arterial pressure (SAP) but did not alter PAP. In PH beagles, ET-1 infusion increased SAP, which was attenuated by FR139317 (an endothelin type [ET] A receptor antagonist), and produced a dose-dependent decrease in PAP, which was attenuated by RES-701-1 (an ETB receptor antagonist). In PH beagles, FR139317 infusion decreased PAP, and RES-701-1 infusion increased PAP. Sarafotoxin S6c (an ETB agonist) infusion decreased PAP in PH beagles. CONCLUSIONS: These results suggest that endogenous ET-1 is elevated in PH disease and may mitigate PH by acting on ETB receptors.

Animals↗
PubMed1995

Properties of the voltage-gated calcium channels mediating dopamine and acetylcholine release from the isolated rat retina.

We examined the properties of voltage-gated calcium channels mediating endogenous dopamine (DA) and acetylcholine (ACh) release in the isolated rat retina. Application of 30 mM KCl elicited the release of DA and ACh, and these releases were abolished in Ca(2+)-free medium. The high K(+)-evoked DA release was largely blocked by both of omega-agatoxin IVA and omega-conotoxin MVIIC, P- and Q-type calcium channel antagonists, and partly blocked by isradipine, and L-type calcium channel antagonist, and omega-conotoxin GVIA, an N-type calcium channel antagonist. omega-Agatoxin IVA at a small dose, sufficient to block P-type channels alone, was however without effect. On the other hand, the high K(+)-evoked ACh release was partly blocked by omega-agatoxin IVA and omega-conotoxin MVIIC, but was resistant to isradipine and omega-conotoxin GVIA. Flunarizine, a non-selective T-type calcium channel antagonist, did not inhibit the release of DA and ACh. Cd2+ markedly blocked the release of both DA and ACh, Co2+ and Ni2+ slightly blocked the release of DA, and the release of ACh was not blocked by these two divalent cations. These results suggest that the high K(+)-evoked release of retinal DA is largely mediated by omega-agatoxin IVA and omega-conotoxin MVIIC sensitive calcium channels (probably Q-type channels), while the release of retinal ACh is largely mediated by as yet uncharacterized Cd2+ sensitive calcium channels. The properties of voltage-gated calcium channels involved in the release of ACh in the rat retina differ from those of DA.

Acetylcholine↗
PubMed1995

Nerve growth factor stimulates tyrosine phosphorylation of paxillin in PC12h cells.

Nerve growth factor (NGF) induces tyrosine phosphorylation of various cellular proteins to activate multiple signal transduction pathways. We show that one of these proteins is paxillin, a cytoskeletal component associated with adhesion plaques. Phospho-amino acid analysis showed that NGF stimulated phosphorylation of its serine in addition to tyrosine residues. Tyrosine phosphorylation of paxillin by NGF was blocked by the pretreatment of the cells with cytochalasin D, an inhibitor of actin polymerization. These results suggest that phosphorylation of paxillin is involved in the signaling pathway of NGF in PC12 cells.

Animals↗
PubMed1995

Effects of modified low density lipoprotein and hypoxia on the expression of endothelial leukocyte adhesion molecule-1.

OBJECTIVES: Expression of endothelial leukocyte adhesion molecule (ELAM-1 or CD62E) plays a role as an early event of atherogenesis. It is well known that interleukin-1 (IL-1) expresses ELAM-1 on vascular endothelial cells. We have examined pathological factors that induce ELAM-1 expression on cultured endothelial cells. METHODS: Examined factors were native low density lipoprotein (LDL), oxidized LDL, glycated LDL, hypoxia, and IL-1. Peroxidation of LDL was performed by ultraviolet radiation. Hypoxia was reproduced by adding a hypoxic cell-culture medium that was deoxygenated by use of a vacuum pump and nitrogen gas. Endothelial cells were harvested from a porcine aorta and were allowed to proliferate to be subconfluent in slide chambers. Expression of ELAM-1 was evaluated by counting the number of cells that were characterized by positive staining with the immunohistochemical technique. RESULTS: Without any stimulants, about 6.9% of the endothelial cells expressed ELAM-1. Weakly oxidized LDL (12 pmol/micrograms protein) significantly expressed ELAM-1 (14.8%) after an incubation period of 1 hour. Glycated LDL induced significant expressions (12.6%) in a fructosamine concentration of 65 pmol/micrograms protein. A one-hour incubation with a hypoxic culture medium expressed ELAM-1 in 16.3% of the cells. Native LDL did not cause any significant increases in the percentage. IL-1 expressed ELAM-1 in 30% of the cells even with as low a concentration as 3.1 U/ml. CONCLUSIONS: The present study shows that not only IL-1 but also weakly oxidized LDL, glycated LDL, and hypoxia may be possible factors that cause the expression of ELAM-1.

Animals↗
PubMed1995

Infection with Nippostrongylus brasiliensis induces invasion of mast cell precursors from peripheral blood to small intestine.

Precursors of mast cells were defined as cells that formed mast-cell colonies in methylcellulose culture (CFU-mast). Mononuclear cells (MNC) were obtained from the bone marrow, peripheral blood, and small intestine of Ws/Ws rats with a small deletion at the tyrosine kinase domain of c-kit and of control normal (+/+) rats. In the culture containing concanavalin A-stimulated spleen cell conditioned medium (ConA-SCM) alone, the numbers of mast-cell colonies produced by Ws/Ws MNC were comparable with those of +/+ MNC. In the culture containing both ConA-SCM and stem cell factor (a ligand of c-kit), however, the numbers of mast-cell colonies produced by +/+ blood MNC were 107 times as great as that of Ws/Ws blood MNC. Using this culture condition, we investigated changes in concentration of CFU-mast in the marrow, blood, and intestine of +/+ rats after infection with Nippostrongylus brasiliensis (NB), which induced marked mast-cell accumulation in the small intestine. The concentration of CFU-mast in blood dropped to 21% of preinfection levels 1 week after the NB infection. In contrast, a sevenfold increase of CFU-mast occurred in the small intestine. The proportion of CFU-mast in S phase of the cell cycle remained at low levels in the marrow and blood after NB infection, but it increased significantly in the small intestine. The present result suggests that NB infection induces the invasion of CFU-mast into the intestine from blood and their subsequent proliferation in the tissue site.

Animals↗
PubMed1995

Control of lymphopoiesis by p50csk, a regulatory protein tyrosine kinase.

The csk gene encodes a nonreceptor protein tyrosine kinase that acts in part by regulating the activity of src-family protein tyrosine kinases. Since the src-family kinases p56lck and p59fyn play pivotal roles during lymphocyte development, it seemed plausible that p50csk might contribute to these regulatory circuits. Using a gene targeting approach, mouse embryonic stem cell lines lacking functional csk genes were generated. These csknull embryonic stem cells proved capable of contributing to many adult tissues, notably heart and brain. However, although csknull progenitors colonized the developing thymus, T and B cell differentiation were both blocked at very early stages. This represented a relatively selective interdiction of lymphocyte maturation, since csknull hematopoietic progenitors supported the development of normal-appearing MAC-1+ blood leukocytes, and the successful maturation of granulocyte/macrophage-colony-forming units from fetal liver progenitors. We conclude that p50csk regulates normal lymphocyte differentiation, but that it almost certainly does so by acting on targets other than p56lck and p59fyn.

Alleles↗
PubMed1995

T cell receptor-mediated stimulation of mouse thymocytes induces up-regulation of the GM2/GD2 synthase gene.

cDNA clones of the mouse GM2/GD2 synthase (EC 2.4.1.92) gene were isolated, and their analyses revealed that the protein has a type II transmembrane structure with 533 amino acids, which was very similar to the human homolog except for the mRNA size. The mRNA level in thymocytes dramatically increased after treatment with anti-CD3 monoclonal antibody, whereas it was not elevated when treated with prostaglandin E2. In situ hybridization showed an elevation of mRNA levels in medullar thymocytes, suggesting that T cell receptor-mediated signaling induces up-regulation of the GM2/GD2 synthase gene in mature thymocytes.

Amino Acid Sequence↗
PubMed1995

The SMS1 gene encoding a serine-rich transmembrane protein suppresses the temperature sensitivity of the htr1 disruptant in Saccharomyces cerevisiae.

A new gene (SMS1; serine-rich multi-copy suppressor) of Saccharomyces cerevisiae was isolated by the ability to suppress the temperature sensitivity of the htr1 disruptant (Kikuchi et al. (1994) Mol. Gen. Genetics, in press) by increasing its gene dosage. The predicted gene product contains a serine-rich domain followed by a putative transmembrane region. The SMS1 gene was physically and genetically mapped in the region near cdc3 on chromosome XII R.

Amino Acid Sequence↗
PubMed1995

Mislocalization of oskar product in the anterior pole results in ectopic localization of mitochondrial large ribosomal RNA in Drosophila embryos.

Mitochondrial large ribosomal RNA (mtlrRNA) was identified as a cytoplasmic factor that induces pole cells in uv-irradiated embryos and is localized on polar granules in normal embryos at early stages. Here, we report that mtlrRNA is localized in the anterior pole if oskar products are forced to be localized there. This clearly shows, contrary to the previous report by Ding et al. (1994, Developmental Biology 163, 503-515), that localization of mtlrRNA depends on oskar function even at the anterior pole.

Animals↗
PubMed1995

Indocyanine green videoangiographic findings in choroidal metastatic tumor.

BACKGROUND: Indocyanine green videoangiography (ICGV) has recently advanced and become widely available as a clinical tool. We tested the efficacy of ICGV in evaluating metastatic choroidal tumors. METHODS: ICGV using Topcon 50-IA was performed in five patients with clinically diagnosed choroidal metastatic tumors. The findings were compared with those of conventional fluorescein angiography (FAG). RESULTS: Compared with FAG, ICGV demonstrated more smooth and regular hypofluorescent lesions, precisely indicating the exact size of the tumor. In all cases, no tumor vessels were found. The choroidal vascular integrity around the tumors was observed. FAG, however, was more sensitive in detecting the tumor development than ICGV when the extent of the hypofluorescent lesion could be seen clearly in the early phase. FAG provided more information regarding retinal pigment epithelial dysfunction in the outer blood retinal barrier overlying the tumor. CONCLUSION: Since ICGV enables visualization of tumors through the retina, it is very useful, particularly in cases of associated secondary retinal detachment around the tumors. ICGV combined with FAG provides more precise assessment of the tumors themselves and their response to treatment than FAG alone.

Adenocarcinoma↗
PubMed1995

Acute left atrial thrombus causing cardiogenic shock following mitral valve replacement: report of a case.

We report herein the rare case of a 53-year-old woman who developed cardiogenic shock due to an acute left atrial thrombus following replacement of the mitral valve. A definitive diagnosis was not able to be made using precordial echocardiography because of the broad, flat shape of the thrombus; however, transesophageal echocardiography imaged the thrombus in detail. The patient was initially stabilized by percutaneous cardiopulmonary support after which a thrombectomy was successfully performed.

Echocardiography, Transesophageal↗
PubMed1995

Sutureless anastomosis using a biofragmentable anastomosis ring.

The biofragmentable anastomosis ring (BAR) is composed of polyglycolic acid and barium sulfate. When used for intestinal anastomosis, the BAR fragments after the anastomosis is established. We used this device in 43 patients. In three patients, the anastomosis with BAR was abandoned due to technical difficulties. A total of 43 anastomoses with BAR were performed in 40 patients. The operations in which BAR was used included right hemicolectomy in 12 patients, transverse colectomy in 7, sigmoidectomy in 11, small bowel resection in 5 and other bowel resections in 8. The time spent for the BAR anastomsis ranged from 7 to 30 min with a mean of 15.2 min, which was significantly shorter than that of conventional hand-sutured anastomosis in 23 cases. The fragmentation and excretion of the BAR occurred from 14 to 49 days later with a mean of 21.8 days. There was only one instance of anastomotic leakage (1/40, 2.5%), which occurred in a patient with a cytomegaloviral infection of the intestine. A postoperative barium enema study in 28 patients showed no passage disturbance through the anastomosis. In conclusion, the anastomosis using BAR is considered to be a simple, safe, and fast method for performing either colonic or small intestinal anastomosis.

Adult↗
PubMed1995

Left ventricular thrombosis following coronary artery bypass grafting in a patient with nephrotic syndrome: report of a case.

We present herein the case of a 63-year-old man with nephrotic syndrome who developed an apical infarction 4 days after undergoing coronary artery bypass grafting. Echocardiography done 2 weeks postoperatively revealed a left ventricular thrombus which was successfully removed. He has no further thrombotic events since anticoagulant therapy was initiated.

Coronary Artery Bypass↗
PubMed1995

Characteristic antitumor activity of cytarabine ocfosfate against human colorectal adenocarcinoma xenografts in nude mice.

The antitumor activity of cytarabine ocfosfate (SPAC) was tested against human colorectal, gastric and lung adenocarcinoma xenografts in nude mice in comparison with the activities of various antitumor drugs used clinically. SPAC showed higher therapeutic efficacy against human colorectal adenocarcinoma xenografts than against human gastric and lung adenocarcinoma xenografts. SPAC was effective against three of four human colorectal adenocarcinoma xenografts, with efficacy higher than that of 1-beta-D-arabinofuranosylcytosine, fluorouracil, cisplatin, doxorubicin, pirarubicin and vindesine sulfate, but lower than that of mitomycin C and cyclophosphamide. These results indicate that SPAC may be useful for induction and/or postoperative chemotherapy against colorectal adenocarcinomas.

Adenocarcinoma↗
PubMed1995

Expression of alpha 2,8-sialyltransferase (GD3 synthase) gene in human cancer cell lines: high level expression in melanomas and up-regulation in activated T lymphocytes.

GD3 Synthase (alpha 2,8sialyltransferase) (EC 2.4.99.8) cDNA has been cloned by eukaryotic cell expression cloning. Using this cDNA as a probe, the expression level of the gene in human cancer cell lines was analysed by Northern blotting and RT-PCR, then correlated with the ganglioside expression and enzyme activity. Melanoma cell lines showed extremely strong bands in Northern blot and RT-PCR/Southern analysis. The enzyme activity was also very high in melanomas as expected. Neuroblastoma and astrocytoma lines showed relatively low levels of the gene expression, whereas they expressed high levels of GD2. Although the mRNA level of the GD3 synthase gene and enzyme activity in individual cell lines correlated positively, some cell lines showed much higher activity than expected from the mRNA level. Among leukaemia lines, adult T cell leukaemia-associated (HTLV-I+) lines showed fairly high levels of the mRNA. On the other hand, T-ALL lines showed very low levels. In addition, GD3 and GD2 expression and mRNA level of the gene during T lymphocyte activation were analysed. Only GD3 expression was induced by any of the stimulatory reagents used, and corresponding up-regulation of the GD3 synthase gene was shown in RT-PCR/Southern analysis.

Base Sequence↗