Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 361 records · Page 20Linked to original sources

PubMed1997

Activation of angiotensin II-forming chymase in the cardiomyopathic hamster heart.

BACKGROUND: Angiotensin (ANG) II plays crucial roles in promoting cardiovascular tissue remodeling. Human chymase catalyzes ANG II formation, whereas rat chymase (rat mast cell protease 1) degrades ANG I to inactive fragments. Such species differences should be considered when the functions of chymase in human cardiovascular diseases are investigated assuming an analogy with animal models. OBJECTIVE: To further characterize the recently identified ANG II-forming hamster chymase, and to analyze pathophysiologic roles played by chymase in the cardiomyopathy of the hamster. METHODS: The gene organization and the primary structure of hamster chymase were determined through molecular cloning. Chymase and angiotensin converting enzyme messenger RNA levels, and chymase-like and angiotensin converting enzyme activities were measured in the heart of BIO 14.6 cardiomyopathic hamsters aged 4, 12, and 25 weeks. RESULTS: The hamster chymase gene is 3 kb long. It has five exons and four introns, and the deduced amino-acid sequence was homologous to other mammalian chymases. The chymase messenger RNA levels and chymase-like activities in the BIO 14.6 hamster hearts were increased significantly at the ages of 12 weeks (the fibrotic stage) and 25 weeks (the hypertrophic stage), but not at age 4 weeks (the premyolytic stage). CONCLUSIONS: These results indicate that heart chymase is activated concurrently with the development of cardiomyopathy. Thus, we conclude that heart chymase could play the primary role in accelerating ANG II formation, thereby causing deleterious changes in the cardiomyopathic heart.

Amino Acid Sequence↗

PubMed1997

Short-term effect of portal vein arterialization on hepatic protein synthesis and endotoxaemia after extended hepatectomy in dogs.

To assess the effect of partial portal arterialization on the remaining liver after usually lethal extended hepatectomy, 30 mongrel dogs underwent 84% partial hepatectomy and were divided into three groups as follows: group 1, 84% partial hepatectomy (n = 10); group 2, 84% partial hepatectomy and splenectomy (n = 10); group 3, 84% partial hepatectomy and splenectomy and splenic artery-vein (A-V) shunt (n = 10). Another five dogs were pre-operatively killed normal controls. Portal vein flow (PVF) decreased to about 60% in groups 1 and 2, but PVF in group 3 was maintained at the pre-operative level. Oxygen saturation of portal vein blood increased markedly, to between 83% (group 1) and 88% (group 3). Portal vein pressure (PVP) increased in groups 1 and 2 by 1.6 to 1.7 times the pre-operative value, but no significant difference in PVP, serum aspartate aminotransferase (AST) and arterial ketone body ratio was found between the three groups. Plasma endotoxin levels after 84% partial hepatectomy were significantly lower in group 3 than in groups 1 and 2. Both of hepatocellular and secretory protein synthesis were enhanced in group 3 compared with the other two groups. These results suggest that partial portal arterialization using a splenic A-V shunt might bring about a beneficial effect on remaining liver function after extended hepatectomy.

Animals↗

PubMed1997

Surgical approach to tumor thrombus of renal cell carcinoma at the level between hepatic vein and diaphragm.

BACKGROUND: The curative resection of tumor thrombus of renal cell carcinoma often provides a good prognosis, but the best surgical method for resection at the level between hepatic vein and diaphragm is still a matter of controversy. METHODS: We performed transabdominal surgery without cardio-pulmonary bypass on 4 patients with tumor thrombus at the level between hepatic vein and diaphragm. The surgical procedures were as follows: The right lobe of the liver was separated and detached from the retroperitoneum, and then the vena cava was clamped just below the diaphragm simultaneous with clamping the porta hepatis. After complete circulatory isolation of the vena cava, the tumor thrombus was resected. RESULTS: There were no severe complications postoperatively. Two patients died of cancer 18 and 38 months after surgery, and the other 2 are alive without evidence of disease after 62 and 66 months. CONCLUSION: This anatomically rational approach is thought to be a good alternative to the pull-through method or cardio-pulmonary bypass for removing a tumor thrombus at this level.

Carcinoma, Renal Cell↗

PubMed1997

Plasmapheresis in the treatment of rapidly progressive glomerulonephritis.

The present study was carried out to examine the efficacy of plasma exchange in patients with rapidly progressive glomerulonephritis (RPGN). Seventeen patients with RPGN were treated with plasmapheresis as adjunct to immunosuppressive therapy. Of these, 4 had antiglomerular basement membrane (GBM) antibody-mediated glomerulonephritis (GN), 8 had immune-complex GN (5 SLE, 2 HSP, 1 cryoblobulinemia), 5 had pauci-immune GN (3 peripheral antineutrophil cytoplasmic antibody [P-ANCA], 1 cytoplasmic antineutrophil cytoplasmic antibody [C-ANCA], 1 other). Treatment of 10 of these patients with plasmapheresis within the first month of disease onset resulted in a stable renal function for a period extending from 1 to 3 years, except in 2 patients who had high baseline levels of serum creatinine. In the remaining patients, 2 were treated with hemodialysis 6 years later at the end of follow-up. We conclude that plasmapheresis, when used in combination with immunosuppressive drugs, is beneficial, leading to improved renal function.

Basement Membrane↗

PubMed1997

Biodistribution of cyclosporin encapsulated in liposomes modified with bioadhesive polymer.

The purpose of this investigation was to study the possibility of renewing the immunosuppressive activity of cyclosporin by formulating the compound in liposomes modified with bioadhesive polymers. The liposomes prepared were evaluated both pharmacokinetically and pharmacodynamically. Tissue distribution and plasma pharmacokinetics of cyclosporin and model dye, sudan black, which is as hydrophobic as cyclosporin, were studied in rats after intravenous infusion (10 mg kg-1). The immunosuppressive efficacy of liposomal cyclosporin preparations was studied in the allogenic rat-heart-transplantation model, where cyclosporin therapy (10 mg kg-1) continued for one week. The entrapment of sudan black in liposomes modified with bioadhesive polymers resulted in higher sudan black delivery to the spleen and the liver than with standard sudan-black-loaded liposomes. Among the modified liposomes, those modified with carbopol 941 showed the most remarkable enhancing effect on the delivery of sudan black to these organs and total plasma clearance of sudan black decreased to 38.6 +/- 7.8 mL h-1 kg-1 (standard liposomes, 58.9 +/- 6.4 mL h-1 kg-1). Delivery of cyclosporin to the spleen and the liver was increased approximately twofold by modifying the liposomes with carbopol 941. In the preliminary study on the allogenic rat-heart-transplantation model, the mean survival days of the graft were 18.8 +/- 2.9 days for the group receiving cyclosporin liposomes modified with carbopol 941, 14.2 +/- 4.4 days for the group receiving standard cyclosporin liposomes and 7.6 +/- 0.5 days for the group receiving cyclosporin solution. The encapsulation of cyclosporin in liposomes modified with bioadhesive polymer enhanced the residence time of cyclosporin in the systemic circulation, resulting in approximately twofold greater delivery of cyclosporin to the spleen and liver. However, in the allogenic rat-heart-transplantation model no significant difference was detected between the immunosuppressive efficacy of cyclosporin encapsulated in bioadhesive polymer-modified liposomes and that encapsulated in standard liposomes.

Acrylic Resins↗

PubMed1997

[Cytomegalovirus retinitis in a patient with systemic lupus erythematosus].

We report a rare case of cytomegalovirus (CMV) retinitis in association with systemic lupus erythematosus (SLE). A 36-year-old female was admitted to our hospital because of nephrotic syndrome and renal insufficiency due to lupus nephritis. After steroid and immunosuppressant treatment for lupus nephritis, she began to complain of floaters and visual disturbance. She was diagnosed as having CMV retinitis based upon the depressed immune status and the clinical appearance of fundus. As soon as CMV retinitis was diagnosed, antiviral treatment with intravenous ganciclovir was instituted and maintained for 7 months. She was treated successfully and almost no progression or relapse of CMV retinitis was documented without ganciclovir maintenance treatment during a 2 year follow-up period. It is suggested that CMV retinitis can occur in patients with SLE treated with steroid and immunosuppressant, indicating the importance of early diagnosis and treatment for CMV retinitis.

Adult↗

PubMed1997

Analysis of phosphorylation of pRB and its regulatory proteins in breast cancer.

AIM: In order to study the role of retinoblastoma protein (pRB) in breast cancer, the phosphorylation of pRB and the expression of its related proteins-such as cyclin E, cyclin dependent kinase 2 (Cdk2), and p21/Cdk interacting protein 1 (Cip1)-were examined in 30 breast cancers in which pRB overexpression was confirmed immunohistochemically. METHODS: The phosphorylation of pRB for 30 tumours was investigated with western blotting. The expression of pRB, Cdk2/Cdc2, cyclin E, and p21/Cip1 was identified by immunohistochemistry and western blotting. RESULTS: The expression of pRB was confirmed in 52 of 70 tumours (74%) by immunostaining. Western blotting for pRB showed that 25 of 30 representative cancers (83%) were underphosphorylated, while only five tumours showed the hyperphosphorylated form of pRB. However, cyclin E and Cdk2-which promote phosphorylation of pRB-were expressed in all tumours. On the other hand p21/Cip1, a Cdk2 inhibitor, was expressed in 18 of 25 tumours with underphosphorylated pRB, while four of the five tumours with hyperphosphorylated pRB showed no expression of p21/Cip1. Examination of the relation between pRB phosphorylation and clinicopathological variables showed that the underphosphorylated group was characterised by low risk of lymph node metastasis (p < 0.01). CONCLUSIONS: The phosphorylation of pRB appears to be regulated mainly by p21/Cip1 through the suppression of cyclin E and Cdk2 in breast cancer. The underphosphorylated form of pRB may be useful as a prognostic factor.

Adult↗

PubMed1997

Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin.

Somatostatin significantly suppressed cell growth of the mouse insulinoma-derived cell line MIN6. MIN6 cells exhibited high-affinity binding of somatostatin with 50% inhibitory concentration value of 0.9 nM. RNA blot analysis revealed that MIN6 cells expressed only SSTR3 among the five somatostatin receptors so far identified. Treatment of MIN6 cells with somatostatin significantly reduced the serum-induced c-fos expression levels. On the other hand, somatostatin (100 nM) treatment of MIN6 cells cultured in medium containing 10% serum transiently increased c-fos expression levels to 282 +/- 4.7% and then significantly decreased them to 27 +/- 7.6% of the levels before treatment. Mitogen-activated protein (MAP) kinase activity transiently increased to 656 +/- 91.2% and decreased thereafter to 39 +/- 13.3% of the activity before the addition of somatostatin (100 nM) into the medium. In addition, the stimulatory effect of somatostatin on c-fos expression and MAP kinase activity (early effect) was not altered by pertussis toxin (PTX), whereas the suppressive effect of somatostatin on c-fos expression and MAP kinase activity (late effect) was mitigated by PTX. These findings suggest that an inhibition of c-fos expression mediated by cross talk between PTX-sensitive G protein signaling and receptor tyrosine kinase signaling is one of the mechanisms by which somatostatin inhibits cell growth in MIN6 cells.

Animals↗

PubMed1997

Differences in brain metabolites between patients with autism and mental retardation as detected by in vivo localized proton magnetic resonance spectroscopy.

We performed volume-selective proton magnetic resonance spectroscopy (1H-MRS) of the brain with a 1.5 T magnet in 28 patients with autism, and compared the results with those from 28 age-matched patients with unclassified mental retardation and 25 age-matched healthy children. Peaks for N-acetylaspartate, choline and creatine, but not lactate, were observed in each group on 1H-MRS. The N-acetylaspartate/choline ratio was lower in patients with mental retardation than in patients with autism and controls (P = .05, respectively). However, there were no differences in the N-acetylaspartate/ choline ratios between patients with autism and controls, and the N-acetylaspartate/creatine and choline/creatine ratios did not differ among the three groups. These results suggest that N-acetylaspartate is decreased in patients with mental retardation and that a disorder or dysfunction of neurons in the brain exists. There also appear to be differences in the brain lesions or dysfunctions found in patients with autism and mental retardation.

Aspartic Acid↗

PubMed1997

Pharmacological profiles of a novel non-peptide angiotensin II type I receptor antagonist HR720 in vitro and in vivo.

The pharmacological properties of 2-butyl-4-(methylthio)-1-[[2'-[[[(propylamino)carbonyl] amino]sulfonyl](1,1'-biphenyl)-4-yl]methyl]-1H-imidazole-5-carboxylate (HR720), a novel non-peptide angiotensin (Ang) II type I (AT1) receptor antagonist, were characterized in both in vitro and in vivo systems. In vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand revealed that HR720 competitively inhibited the specific binding of the ligand to the adrenal cortex. The IC50 value for the adrenal cortex was 1.5 x 10(-8) M, and the IC50 for medulla was 1.4 x 10(-6) M. Similar results were obtained in the adrenal cortex with CV-11974, a known potent AT1-receptor antagonist. Since AT1 receptors are known to predominate in the adrenal cortex and AT2-receptors in the adrenal medulla, it is considered that HR720 is highly selective for AT1 receptors. HR720 inhibited the Ang II-induced contraction of isolated rabbit aortic strips and human gastroepiploic arteries in a noncompetitive manner, pD'2=9.40 and 9.62 for rabbit aorta and human artery, respectively. With CV-11974, pD'2 values of 9.84 in isolated rabbit aorta and 10.00 in human artery were obtained. HR720 did not affect the norepinephrine-, serotonin- or KCl-induced contraction even at a concentration of 1 x 10(-5) M. In anesthetized hamsters, HR720 induced a dose-dependent inhibition of the pressure response to Ang II. The potency of HR720 to antagonize the Ang II-induced pressure response was similar to that of CV-11974. These results demonstrate that HR720 is a potent and selective AT1-receptor antagonist.

Adrenal Glands↗

PubMed1997

Involvement of IL-4 in human glomerulonephritis: an in situ hybridization study of IL-4 mRNA and IL-4 receptor mRNA.

Interleukin-4 (IL-4) has been recently implicated in the pathogenesis of glomerulonephritis. However, the expression of IL-4 and IL-4 receptor (IL-4R) in human kidney has not been fully determined. Nonradioactive in situ hybridization was used to examine the expression of IL-4 mRNA and IL-4R mRNA in tissues from normal kidneys and specimens from a variety of human kidney diseases. In normal glomeruli, a few mesangial cells and cells of the Bowman's capsule weakly expressed IL-4 and IL-4R mRNA, whereas in diseased glomeruli both mRNA types were strongly expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells, and cells of the Bowman's capsule. The relationship between the expression of these mRNA and the degree of glomerular injury was different in different types of glomerulonephritis. In IgA nephropathy and non-IgA mesangial proliferative glomerulonephritis, IL-4 expression correlated positively with the degree of mesangial hypercellularity and extracellular matrix expansion. However, IL-4R expression was relatively constant. In contrast, the expression of IL-4 and IL-4R mRNA correlated negatively with the degree of glomerular injury in lupus nephritis. Coexpression and discordant expression of these mRNA forms were observed in individual cells. In tubulointerstitium with severe lesions, IL-4 mRNA and IL-4R mRNA were observed in atrophic tubules and some of the infiltrating cells and fibroblasts. The interstitial expression of these mRNA forms was similar in IgA nephropathy, non-IGA mesangial proliferative glomerulonephritis, and lupus nephritis and correlated positively with the degree of tubulo-interstitial changes. These results suggest that an autocrine and/or paracrine pathway of IL-4 is present in human diseased kidneys and that IL-4 may be involved in tissue injury in glomerulonephritis.

Adult↗

PubMed1997

Comparison of cellular characteristics between human hepatoma cell lines with wild-type p53 and those with mutant-type p53 gene.

Characteristics of human hepatoma cell lines with the wild-type p53 were compared with those of human hepatoma cell lines with the mutant-type p53. The p21 protein located downstream of p53 was expressed in cell lines with the wild-type p53 but was not expressed in cell lines with the mutant-type p53. As to other tumor suppressor genes such as p16 and p27, there was no difference in their expression between both types of cell lines. In addition, no marked difference was observed in the activities of CDK2 and CDK4 between cell lines with the wild-type and the mutant-type p53. Phosphorylated Rb protein was detected in all cell lines except the HLE line, indicating that this cell line may have a deletion of and/or a mutation of the Rb gene. These results indicate that abnormalities of tumor suppressor genes other than p53, p16, p27, and Rb may be involved in hepatocarcinogenesis. The population doubling time of the wild-type p53 cells was significantly longer than that of the mutant p53 cells. Neither type of cell line showed a specific chromosome distribution which would indicate karyotype instability. The cell lines expressing the wild-type p53 produced tumors at lower frequency than those with the mutant p53 gene. Although there was no significant difference in effects of TGF-beta 1, EGF, cholera toxin, and db-cAMP on cell growth between the two types of cells, all three cell lines with the wild-type p53 were resistant to cytotoxicity of TNF-alpha, while two of the three with the mutant p53 were very sensitive to its cytotoxic effects.

Animals↗

PubMed1997

Yeast functional assay of the p53 gene status in human cell lines maintained in our laboratory.

We used a yeast functional assay (functional analysis of separated alleles in yeast: FASAY) to determine the p53 gene status of human cell lines maintained in our laboratory. This assay enables the researcher to score wild-type p53 expression on the basis of the ability of expressed p53 to transactivate the reporter gene HIS 3 via the p53-responsive GAL 1 promoter in Saccharomyces cerevisiae. The cell lines examined were ten hepatoma, two hepatoblastoma, three in vitro immortalized fibroblast, two osteosarcoma, a chondrosarcoma, an ovarian teratocarcinoma and a colon cancer cell line. Out of 20 cell lines, 11 cell lines had mutations in both alleles of the p53 gene, and another 8 cell lines had no mutation in the p53 gene. Thus, 55% of the cell lines examined had mutations in the p53. Interestingly, PA-1 cells had both the normal and the mutant p53 alleles, showing that FASAY is a useful method for detecting the wild-type and mutated p53 genes simultaneously. As for the three liver cell lines harboring HBsAg, there was no relationship between their p53 gene status and the presence of HBsAg. Two cell lines were normal for p53 status, while the other had a mutation of the p53 gene.

Alleles↗

PubMed1997

Endovascular stenting of a traumatic dissecting aneurysm of the extracranial internal carotid artery--case report.

A 57-year-old male presented with a traumatic dissecting aneurysm of the distal, extracranial internal carotid artery (ICA). Stent placement resulted in complete occlusion of the aneurysm and preservation of the carotid blood flow. He also had an atherosclerotic stenosis of the ipsilateral middle cerebral artery, which was uneventfully treated by angioplasty 3 months after stent placement. Endovascular reconstruction of the ICA with a stent may be the best way to occlude dissecting aneurysms, especially in patients who cannot tolerate ICA occlusion, are at risk from delayed ischemia, or have wide-necked or multiple aneurysms.

Aortic Dissection↗

PubMed1997

[31P magnetic resonance spectroscopy(MRS) study in basal ganglia of patients with Parkinson's disease].

We report 31P magnetic resonance spectroscopy(MRS) to study regional high energy phosphate and phospholipid metabolism in basal ganglia of patients with Parkinson's disease(PD) in comparison with normal controls. The ratio of phosphomonoester(PME)/phosphocreatine(PCr), phosphodiester(PDE)/PCr and total Adenosine triphosphate(ATP) tend to decrease and the ratio of PDE/PME tend to elevate compared with controls. Moreover these findings are correlated with the duration of illness. Our results suggest that neural elements in basal ganglia may be damaged in PD. In conclusion, 31P-MRS appears to be useful for the study of neural damage and degeneration in vivo.

Adenosine Triphosphate↗

PubMed1997

Further classification of dysmotility-like dyspepsia by interdigestive gastroduodenal manometry and plasma motilin level.

OBJECTIVE: To investigate interdigestive gastroduodenal motility with an infused catheter and measure plasma motilin levels in eight normal individuals and 18 patients with dysmotility-like dyspepsia. METHODS AND RESULTS: All normal individuals had normal gastroduodenal interdigestive migrating complexes. Patients with dysmotility-like dyspepsia were classified into three subgroups on the basis of gastric antral motility: 1) seven patients with normal interdigestive migrating complexes, 2) five patients without interdigestive migrating complexes and with gastric phase II predominant over phase I, and 3) six patients without interdigestive migrating complexes and with phase I predominance. The maximum and mean plasma motilin levels were significantly different in normal individuals from those in subgroup 3 (Kruskal-Wallis test, p < 0.05). CONCLUSIONS: Dysmotility-like dyspepsia appears to be a heterogeneous condition. Abnormal motilin secretion may cause dysmotility in subgroup 3, but dyspepsia in subgroup 1 and the absence of interdigestive migrating complexes in subgroup 2 could not be explained only on this basis.

Adult↗

PubMed1997

Hepatic resection of liver metastases from gastric carcinoma.

OBJECTIVES: Previous reports have indicated that results of the surgical resection of hepatic metastases from gastric carcinoma have been unsatisfactory. We therefore evaluated the results of aggressive surgical resection for hepatic metastases from gastric carcinoma, to identify candidates with a better likelihood of survival. METHODS AND RESULTS: Twenty-one patients with synchronous or metachronous hepatic metastases from gastric carcinoma underwent hepatic resections. Five patients were still alive, without recurrence, at 10, 41, 46, 117, and 176 months after their hepatic resection. Sixteen patients died of recurrence 5-33 months (mean, 10 months) after hepatic resection. A significant difference in the number of node metastases (solitary or multiple) and in the tumor-free margin of the resection (< 10 mm or > 10 mm) was found between survivors and those who died. CONCLUSION: Hepatic resection for hepatic metastases from gastric carcinoma may improve the prognosis in patients with a solitary metastasis if adequate tumor-free margins (> 10 mm) can be obtained.

Aged↗

PubMed1997

[Difference of blood cell counts with reference blood cell counters in different makers: Part II].

This is the second report of evaluation on the difference of blood cell counting among different automated blood cell counters in Japan. We tested reference blood cell counters of 6 different companies: Coulter, Sysmex, Bayer-Sankyo, Nihon Kohden, Horiba and Dainabot. Forty ml of whole blood were taken from 3 healthy persons and EDTA-2K anticoagulated blood samples (Sample 1, 2 and 3) were sent to each company to determine blood cell counts with a reference automated counter. As a result, the following items showed more than 10% difference among makers: RBC between Dainabot and Horiba in Sample 3, hematocrit values between Coulter and Dainabot in Sample 2, WBC between Nihon Kohden and each of three makers (Sysmex, Horiba and Dainabot) in all 3 samples and that between Bayer-Sankyo and each of two makers (Sysmex and Horiba) in Sample 3 and platelet count between Dainabot and each of 3 makers (Bayer-Sankyo, Nihon Kohden and Horiba) in all 3 samples. The following items showed difference between 5 and 10%: MCV between Coulter and each of two makers (Bayer-Sankyo and Horiba), WBC between each of two makers (Coulter and Nihon Kohden) and each of other 4 makers, and platelet count between each of two makers (Nihon Kohden and Horiba) and each of 3 makers (Coulter, Sysmex and Bayer-Sankyo). Recently Japanese Committee for Clinical Laboratory Standards proposed minimum clinical allowance of blood cell count as follows: hemoglobin 3%, RBC 4%, MCV 4%, WBC 7% and platelet count 10%. It is suggested that all of the items showing the difference more than above allowance among makers should be improved for clinical use to have good external quality control in blood cell counting by automated instruments.

Blood Cell Count↗