Search PubMed⌕ Search

Biomedical subjects

M Mizuno

Publications and source records attributed to M Mizuno.

At least 235 records · Page 13Linked to original sources
PubMed1996

Regulation of very-low-density lipoprotein receptor in hypertrophic rat heart.

To elucidate the regulation of very-low density-lipoprotein (VLDL) receptor, we have studied its gene expression in the heart of spontaneously hypertensive rats-stroke prone (SHR-SP, an animal model for hypertension-induced cardiac hypertrophy) compared with Wistar-Kyoto rats. RNase protection assay showed that ventricular VLDL receptor mRNA falls to 41% of normal levels at 4 weeks when hypertension is not yet fully developed, and drops further to 14% at 13 weeks, when cardiac hypertrophy is established. Lipoprotein lipase mRNA decreases in parallel with VLDL receptor mRNA. In cultured neonatal rat ventricular cardiomyocytes, VLDL receptor mRNA decreases in parallel with the process of cardiocyte hypertrophy during the 24 hours after treatment with 10-8 mol/L endothelin-1, falling to 40% of the initial value. These results demonstrate that there is downregulation of VLDL receptor gene expression in cardiac hypertrophy both in vivo and in vitro and suggest that the regulation of the VLDL receptor is possibly linked with the switch in energy substrate from lipid to glucose known to occur in cardiac hypertrophy.

Animals↗
PubMed1996

Variable expression of human transgenes in SHN mice.

The mouse mammary tumour virus/human transforming growth factor alpha (MMTV/hTGF alpha) gene or the mouse whey acidic protein/human growth hormone (mWAP/hGH) gene was introduced to a high mammary tumour strain of SHN virgin females by mating with males bearing each gene. We maintained transgenic mice by backcrossing males with the hTGF alpha transgene or high serum hGH levels (> 50 ng/ml) to SHN virgins in the subsequent generations. Expression of the transgenes was examined at each generation. At the first and the second generations of backcrossing (N1 and N2), females showed hTGF alpha mRNA in the mammary glands associated with a marked outgrowth of the glands. Both females and males had high hGH levels in the circulation, but these characteristics disappeared completely after the third generation (N3). All findings indicate that SHN mice are specific in the resistance to the expression of some human transgenes.

Animals↗
PubMed1996

Primary sclerosing cholangitis in Japanese patients: association with inflammatory bowel disease.

To characterize primary sclerosing cholangitis (PSC) in Japanese patients and its association with inflammatory bowel disease (IBD), 155 reported cases of PSC, including 6 cases of our own, were reviewed. The prevalence of IBD was less in Japanese PSC patients than in Western patients (23% versus 62-100%). Japanese PSC patients with IBD were younger (mean age, 33.1 versus 51.8 years) and were more often women (51% versus 36%) than those without IBD. Seventy-four percent of PSC patients with IBD had extensive colonic lesions, and 89% of those developed IBD simultaneously, with or prior to PSC. There were 3 cases of neutrophilic cholangitis among the PSC patients with IBD but none in those without IBD. Based on these observations, we speculate that there may be subtypes of PSC which differ pathophysiologically.

Adolescent↗
PubMed1996

Repeated exposure to cationic immunoliposomes activates effective gene transfer to human glioma cells.

The use of whole immunoglobulin G (IgG) and F(ab')2 of the G-22 monoclonal antibody associated with cationic liposomes (immunoliposomes) and the effect of repeated exposure were investigated for the transfection of the LacZ gene to various glioma cell lines. Immunoliposomes associated with either whole IgG or F(ab')2 monoclonal antibody caused an about 2-fold increase in beta-galactosidase activity compared with liposomes associated with no antibody in glioma cell lines expressing the CD44 antigen. beta-Galactosidase activity was further increased by about 2-fold by repeated exposure compared with single exposure. A glioma cell line not expressing the CD44 antigen showed no such increase in beta-galactosidase activity. These results indicate that repeated exposure of cationic immunoliposomes achieves a higher transfection efficiency and is a potentially effective method of gene therapy for patients with malignant glioma.

Antibodies, Monoclonal↗
PubMed1996

[A case of hepatocellular carcinoma responding to oral administration of 5'-DFUR].

A 65-year-old female patient with liver cirrhosis complicated with hepatocellular carcinoma (HCC) was treated with oral administration of 5'-DFUR (600 mg/day). The titer of serum alpha-fetoprotein gradually decreased, and reduction of the hepatic tumor size was observed by abdominal computed tomography (CT) following 5'-DFUR treatment. HCC was obviously diminished since the start of 5'-DFUR administration and almost disappeared in fifteen months. This case suggests the treatment with 5'-DFUR for hepatocellular carcinoma is completely effective.

Administration, Oral↗
PubMed1996

Gene therapy against an experimental glioma using adeno-associated virus vectors.

The efficacy of gene therapy for glioma was examined using adeno-associated virus (AAV)-based vectors to deliver genes to experimental tumors in mice. Stereotactic injection of 2 x 10(5) U-251SP human glioma cells into the brains of nude mice produced tumors of 19.06 +/- 1.79 mm2 17 days after injection. Employing a high titer preparation of AAV vector containing the gene for beta-galactosidase (AAV-lacZ), dose-dependent transduction of U-251SP cells was seen in vitro. When 1.6 x 10(10) AAV-lacZ particles were directly injected into tumors in vivo, 30-40% of the cells along the needle track expressed beta-galactosidase. Transduction of U-251SP cells in vitro with an AAV vector containing a bicistronic gene encoding both herpes simplex thymidine kinase and human interleukin-2 (AAV-tk-IRES-IL2) rendered them sensitive to the cytocidal effects of ganciclovir (GCV) and IL-2 was produced in a dose-dependent manner. Cocultures of AAV-tk-IRES-IL2 transduced cells and nontransduced cells proved highly sensitive to GCV indicating the contribution of the bystander effect. Stereotactic delivery of 6 x 10(10) AAV-tk-IRES-IL2 particles into day 7 tumors in nude mice followed by administration of GCV for 6 days, resulted in a 35-fold reduction in the mean volume of tumors compared with controls. Normal brains did not suffer from any toxic effect of the administration of AAV-tk-IRES-IL2 and GCV. These results indicate that high titer AAV vector treatment may be safe and effective for in vivo gene therapy of human brain tumors.

Animals↗
PubMed1996

[Examination of percutaneous minocycline hydrochloride injection therapy for hepatic cyst by one puncture method].

Minocycline hydrochloride (MINO) at a dose of 500 mg (in principle) was injected into each of 11 hepatic cysts/10 cases (mean maximum diameter: 12.6 cm) that exhibited symptoms or a tendency toward growth by percutaneous transhepatic one puncture method, and the relation between therapeutic efficacy and pH of cystic fluid was examined. The efficacy was evaluated by abdominal CT after 3 months, and when a shrink of 50% or more in the maximum diameter was observed, it was judged as marked response. Marked effect was observed in 9 lesions of 11 (82%). This MINO injection therapy by one puncture method is very safe, simple and useful. Reduction in intra-cystic pH was not always related to the therapeutic efficacy, so involvement of cytotoxicity of MINO was suggested in degenerating the cystic epithelial cells.

Adult↗
PubMed1995

Initiating and responsible enzyme of arginine vasopressin degradation in human placenta and pregnancy serum.

The hydrolysis of arginine vasopressin (AVP) by human placental subcellular fractions and pregnancy sera was studied in the presence of selective inhibitors and the antibody against pregnancy serum oxytocinase (P-LAP) (EC 3.4.11.3) by measuring liberated amino acids by high-performance liquid chromatography (HPLC). AVP degradation by placental subcellular fractions and pregnancy sera was inhibited by bestatin. The IC50 values of bestatin on AVP degradation by placental subcellular fractions and pregnancy sera were similar to that of this inhibitor on the P-LAP measured by L-Leu-p-nitroamnilide as a substrate (LAP activity), which we reported previously. Our immunotitration study clearly showed that the initiating and responsible protease in AVP degradation in human placenta and pregnancy serum is P-LAP. Since N-benzylcarbonyl-valyl-prolinal (Z-Val-prolinal), a selective inhibitor of post-proline endopeptidase, and phosphoramidon, a putative endopeptidase-24.11 inhibitor, could not significantly influence the degradation of AVP by placental microsomal fractions. Neither enzyme seems to be actively involved in AVP degradation.

Amino Acid Sequence↗
PubMed1995

Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist.

CS-866, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxy-4-(1-hydroxy-1- methylethyl)-2-propyl-1-(4-[2-(tetrazol-5-yl)-phenyl]phenyl)met hylimidazol- 5-carboxylate, a prodrug type angiotensin receptor antagonist, is deesterified to the active acid, RNH-6270. RNH-6270 inhibited [125I]angiotensin II binding to bovine adrenal cortical membranes (angiotensin AT1 receptors) with an IC50 value of 7.7 nM, but not [125I]angiotensin II binding to bovine cerebellar membranes (angiotensin AT2 receptors), indicating the selectivity of the compound for angiotensin AT1 receptors. In guinea pig aortas, RNH-6270 reduced the maximal response of the concentration-contractile curve for angiotensin II (pD'2 = 9.9), but had no effect on the contractile response induced by phenylephrine or KCl. In conscious rats, intravenously injected RNH-6270 inhibited angiotensin II-induced pressor responses in a dose-dependent manner, and orally administered CS-866 produced a long-lasting inhibition of angiotensin II pressor responses. SK&F-525A, a P-450 inhibitor, suppressed the angiotensin II inhibitory effect of losartan, but not that of CS-866. These results demonstrate that RNH-6270 is a potent and AT1-selective angiotensin receptor antagonist and that, after oral administration, CS-866 has a long-lasting angiotensin II inhibitory action which is not affected by drug metabolizing enzymes in the liver.

Adrenal Cortex↗
PubMed1995

TGF-beta accelerated the osteogenic differentiation of bone marrow cells induced by collagen matrix.

Bone marrow cells have multipotency for differentiation. Recently we found that type I collagen matrix induced the osteogenic differentiation of bone marrow cells. In this study we showed that TGF-beta enhanced the effect of collagen matrix on bone marrow cells and accelerated the osteogenic differentiation. These results imply that TGF-beta might play a crucial role in the osteogenic differentiation of bone marrow cells during embryogenesis and the repair of bone.

Alkaline Phosphatase↗
PubMed1995

Transient overexpression of catalase does not inhibit TNF- or PMA-induced NF-kappa B activation.

H2O2 has been proposed as a second messenger involved in cell signaling for NF-kappa B activation. In the present study, this hypothesis was tested by transiently overexpressing catalase, a specific scavenger of H2O2, in COS-1 cells. A mammalian expression vector was constructed by incorporating catalase gene from pCAT10 clone into the unique EcoRI site of the pSG5 vector which contains the SV-40 promoter. Transient transfection of the catalase expression vector by the DEAE-dextran method led to a four-fold increase in catalase activity and catalase content as detected by immunoblot analysis. This level of increase was detected in both nuclear/mitochondrial- and cytosolic/microsomal fractions. Overexpression of catalase, however, did not block TNF- or PMA-induced NF-kappa B activation. These results weaken the hypothesis that H2O2 is a second messenger for TNF- and PMA-signaling for NF-kappa B activation.

Animals↗
PubMed1995

Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-beta.

In our previous study on liposome-mediated transfection of the human interferon-beta (HuIFN-beta) gene into subcutaneously implanted human gliomas in nude mice, we found that HuIFN-beta was produced and secreted by the tumor cells and that the growth of solid tumors was completely inhibited. The present study investigated the growth-inhibitory effect of liposomes containing the HuIFN-beta gene inserted into a vector (pSV2IFN-beta) on T9 rat glioma implanted into the brains of rats. Tumor cells and liposomes containing pSV2IFN-beta or other additives were simultaneously injected into the brains of rats. HuIFN-beta was detected in solid gliomas growing in the brains of rats injected with liposomes and magnetic resonance imaging (MRI) showed that tumor growth was inhibited. In addition, the latent period until the appearance of neurological symptoms was significantly prolonged in rats treated with liposomes containing pSV2IFN-beta. However, the survival time of the treated rats was not significantly increased.

Animals↗
PubMed1995

Stimulation by bone sialoprotein of calcification in osteoblast-like MC3T3-E1 cells.

Bone sialoprotein (BSP) containing an Arg-Gly-Asp cell-binding sequence was purified from bovine bone 4 M guanidine-HCl extract after HCl demineralization by a series of chromatographic procedures. When this protein was coated on culture dishes in the presence of type I collagen, it increased both DNA content and alkaline phosphatase (ALP) activity in osteoblast-like MC3T3-E1 cells, and stimulated calcification in the cells, whereas fibronectin, another cell-binding protein, showed a marked increase in the DNA content but had little effect on the ALP activity. These findings suggest that BSP is mitogenic for preosteoblasts and differentiating the cells into osteoblasts, thereby stimulating bone calcification.

3T3 Cells↗
PubMed1995

Endoscopic detection of ectopic multiple minute sebaceous glands in the esophagus. Report of a case and review of the literature.

This case report describes a patient with a rare form of ectopic sebaceous glands. The patient was a 53-year-old woman complaining of prolapse of a polyp through the anus who was admitted for polypectomy of the rectal polyp. After polypectomy, esophagogastroduodenoscopy was performed to detect other lesions. Although she had no symptoms from an upper gastrointestinal series, such as dysphagia, heartburn, or epigastric pain, multiple yellow rounded elevated lesions arranged in rows, 0.5 mm in diameter and more than 100 in number were observed in the middle and lower esophagus. Histological examination of the biopsied specimens taken from the lesions endoscopically revealed a structure with the characteristics of a sebaceous gland including an excretory duct.

Biopsy↗