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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 109 records · Page 6Linked to original sources
PubMed2001

Beneficial effect of trandolapril on the lifespan of a severe hypertensive model.

It remains to be clarified whether ACE Inhibitors extend the lifespan in cases of severe hypertension. In the present study, we examined whether inhibition of angiotensin-converting enzyme (ACE) would affect mortality in a very severe hypertensive model. Twelve-week-old stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar-Kyoto rats (WKY) were used, and measurements at this age were taken as the basal values. At this age, the systolic blood pressure of SHR-SP was 219+/-4 mmHg, while that of WKY was 102+/-3 mmHg. After 12 weeks of sodium loading, the systolic blood pressure in the placebo-treated SHR-SP reached to 251+/-4 mmHg. At 4 weeks of sodium loading, 85% of the placebo-treated SHR-SP had died, and the systolic blood pressure of the surviving rats was 249+/-26 mmHg. In the trandolapril-treated SHR-SP, the systolic blood pressure was gradually increased to 293+/-5 mmHg at 16 weeks, and none of the mice had died at this time point (0% mortality). The ACE activities of the aorta, brain, heart and kidney were increased in the surviving placebo-treated SHR-SP at 4 weeks compared with the basal levels, while they were significantly decreased in the trandolapril-treated SHR-SP at 16 weeks. These data demonstrate that trandolapril extends the lifespan of this severe hypertensive model, even in cases in which the blood pressure cannot be lowered.

Angiotensin II↗
PubMed2001

Loss of nuclear localization of the S100C protein in immortalized human fibroblasts.

It is well known that cancer develops through a multistep process. In vitro transformation studies of normal human cells have shown that the immortalization step is critical for neoplastic transformation of cells. Furthermore, studies of cell fusion between normal and immortalized cells have indicated that the normal phenotype is dominant and the immortal phenotype is recessive. Thus we looked for cellular proteins that were down-regulated in immortalized human cells by two-dimensional gel electrophoresis to elucidate the mechanisms of immortalization of human cells. We found that the S100C protein was down-regulated in immortalized cells. This protein was localized in the cytoplasm of cells at the semiconfluent stage, while at the confluent stage it moved into the nuclei of normal cells but not into those of immortalized cells. Microinjection of an S100C antibody into normal confluent cells diminished the level of nuclear S100C protein, resulting in DNA synthesis. Taken together, loss of nuclear localization of the S100C protein, which may be related to DNA synthesis, is thought to be one of the mechanisms of immortalization.

Amino Acid Sequence↗
PubMed2001

Syndrome of inappropriate secretion of ADH (SIADH) following cisplatin administration in a pulmonary adenocarcinoma patient with a malignant pleural effusion.

We report a patient with pulmonary adenocarcinoma complicated by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) following systemic chemotherapy with cisplatin (CDDP) and vindesine (VDS). A 66-year-old woman was diagnosed as having pulmonary adenocarcinoma with malignant pleural effusion following investigations for cough and dyspnea. After drainage of the effusion she received combination chemotherapy with CDDP and VDS. She developed SIADH 48 hours following chemotherapy. Interestingly, the use of carboplatin (CBDCA) and VDS in the subsequent treatment course was well tolerated indicating that the SIADH was most likely to have been induced by administration of CDDP.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2001

Duodenal somatostatinoma and erythrocytosis in a patient with von Hippel-Lindau disease type 2A.

A female with von Hippel-Lindau (VHL) disease type 2A first presented with erythrocytosis at the age of 9 years. This patient revealed multiple paragangliomas at age 22. After the removal of tumors, a retinal hemangioblastoma developed. Our diagnosis of VHL disease type 2A was confirmed. Moreover, systemic examination showed a duodenal somatostatinoma. Frequent and long-term monitoring is important for patients with pheochromocytomas or paragangliomas, and a screening for VHL disease and other hereditary cancer syndromes is recommended. Recognition of neuroendocrine tumors as a manifestation of VHL disease permits earlier diagnosis and improves prognosis.

Adult↗
PubMed2001

Japanese alcoholic beverage and all cause mortality in Japanese adult men.

This article examines whether an association is found between quantity of alcohol consumed and all cause mortality, and a relation is detected between types of alcoholic beverage and all cause mortality in Japanese male adults. A cohort study was performed in three towns located in two former coal mine areas and a rural area in Fukuoka. A mail survey was carried out between 1988 and 1990, and was extended in a follow-up period to 1995 (two towns) and 1999 (one town). 6,652 Japanese men aged from 40 to 69 years responded to a questionnaire that included alcohol consumption and smoking habit. The data were analysed with Cox's proportional hazards model. As regards an association between all cause mortality and quantity of alcohol consumed, statistically significant relations were recognized in occasional drinkers and drinkers with less than 25g ethanol per day (hazard ratio= 0.71, 95% CI: 0.50-0.99; hazard ratio= 0.51, 95% CI: 0.29-0.88, respectively). With respect to drinkers with 25-50g/day and > or =50g/day, no significant relation was observed in the risk for all cause mortality. Comparing all cause mortality for daily drinkers and nondrinkers with respect to the beverage types, a risk was lower for daily drinkers than for nondrinkers with every type of beverage studied. In particular, there was a statistically significant adverse association for all cause mortality among subjects who reported drinking Japanese sake compared with nondrinkers (hazard ratio= 0.45, 95% CI: 0.30-0.68). Alcohol consumption (particularly Japanese sake) is likely to be associated with a reduced hazardous ratio of all cause mortality.

Adult↗
PubMed2001

Influence of environmental conditions on dentin bond strengths of recently developed dentin bonding systems.

A study was conducted to investigate the influence of temperature and relative humidity (RH) on the bond strengths of several recently developed dentin bonding systems. Six environmental conditions, (A) 25+/-0.5 degrees C, 50+/-5% RH, (B) 25+/-0.5 degrees C, 80+/-5% RH, (C) 25+/-0.5 degrees C, 95+/-5 % RH, (D) 37+/-0.5 degrees C, 50 +/-5 % RH, (E) 37+/-0.5 degrees C, 80+/-5% RH, (F) 37+/-0.5 degrees C, 95+/-5 % RH were used. Bovine mandibular incisors were mounted in self-curing resin and the facial surfaces were ground on wet #600 SiC paper to expose the dentin. After the tooth surface had been treated according to each manufacturer's instructions, adhesives were applied, followed by condensation of resin composites into a mold placed on the dentin surface. Fifteen specimens per group were stored in distilled water at 37 degrees C for 24 h, and then shear-tested at a cross-head speed of 1.0 mm/min. Statistical analysis was carried out with two-way ANOVA followed by Tukey's test (P<0.05). Dentin bond strengths decreased with increasing relative humidity but were not influenced by environmental temperature. Even though one-bottle adhesive systems require a wet dentin surface, their bond strengths are affected by an increase in environmental humidity.

Alkanes↗
PubMed2001

Systemic fusariosis after a preparative regimen including thiotepa, VP-16 and busulfan used for blood stem cell transplantation in Hodgkin's disease.

Fusarium infection is rare but important infection after bone marrow transplantation (BMT). A 27-year-old man developed systemic fusarial infection following severe skin damage probably caused by high-dose thiotepa administration. Systemic fusariosis rapidly progressed to a variety of organs despite antifungal treatment, and he finally died of this infection on day 75. Considering that this organism usually invades via damaged skin and that the penile lesion was the first manifestation of systemic fusariosis in this patient, careful examination of the skin might be helpful for early diagnosis of fusarial infection. His clinical course provided us with an important clue for diagnosis of fusarial infection.

Adult↗
PubMed2001

Reactivation of liver-specific gene expression in an immortalized human hepatocyte cell line by introduction of the human HNF4alpha2 gene.

An immortalized human hepatocyte cell line (OUMS-29) was established from fetal liver by transfection with the SV-40 large T antigen gene that has certain liver-specific functions such as albumin production and enzyme activities of CYP1A1, 1A2, and 2E1. To make OUMS-29 cells express other liver-specific functions, the human hepatocyte nuclear factor 4alpha2 (HNF4alpha2) gene was introduced into the cells, because this gene was found to be markedly down-regulated. The transduced HNF4alpha2 was overexpressed in the nuclei of the transfected cells, and its DNA-binding activity was also detected. The liver-specific genes such as apolipoprotein AI, CII, CIII, blood coagulation factor X, alpha1-antitrypsin, and HNF1alpha were up-regulated. Thus, this cell line is expected to be a useful tool for studying the differentiated human hepatocyte functions.

Apolipoprotein A-I↗
PubMed2001

Overexpression of platelet-derived growth factor B and downregulation of PDGF-receptor alpha in human immortalized fibroblasts.

Since immortalization of cells is critical in multistep carcinogenesis, efforts should be made to elucidate the mechanisms of the immortalization. To determine whether platelet-derived growth factor (PDGF) signal pathways play a role in immortalization of cells, we compared mRNA expressions of PDGFs and their receptors in three immortalized human fibroblast cell lines (SUSM-1, OUMS-24F, and KMST-6) with their normal parent cells. As a result, mRNA expression of PDGF-B (oncogene: c-sis) was upregulated in these immortalized cells. Unexpectedly, the expression of alpha- and beta-PDGF receptor genes was downregulated. PDGFR-alpha mRNA was remarkably decreased. When exogenous PDGFR-alpha was expressed transiently in the KMST-6 cells, the morphology of the cells resembled that of normal cells. These results suggest that the overexpression of PDGF-B (c-sis) and downregulation of PDGFR-alpha are related to the phenotypic characteristics of immortalized human cells.

Blotting, Northern↗
PubMed2001

Microsatellite instability correlates with normal expression of cyclin E in hepatocellular carcinomas.

It has been reported that microsatellite instability (MSI) strongly correlates with carcinogenesis and cancer progression. In the present study, we studied the incidence of MSI at 5 polymorphic microsatellite markers (D5S406, D13S153, D16S402, D17S796, and poly(A) tract BAT26), the expression of G1 cyclins (cyclin A, cyclin D and cyclin E), and Ki-67 labeling index in 30 surgically resected hepatocellular carcinomas (HCCs) and their adjacent non-cancerous tissues. The results of analysis showed that 43% of HCCs exhibited MSI in one locus, 10% in two loci, and 3% in three loci. Overexpressions of cyclin E and cyclin A were observed in 57% and 83% of HCCs, respectively. MSI in HCCs, however, correlated with normal expressions of cyclin E and cyclin A and with a low labeling index of Ki-67. Thus, patients with HCCs exhibiting MSI at these 5 markers may have less involvement of G1/S disregulation and may have better prognosis than other patients with HCC.

Aged↗
PubMed2001

Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer.

Dickkopfs (Dkks) are secretory glycoproteins and are important for inducing amphibian head formation. Some Dkks have the ability to antagonize the Wnt proto-oncoprotein, which can promote cell proliferation and transformation when it is mutated or overexpressed. We recently cloned the REIC/Dkk-3 gene, one of the Dkks, and found that expression of the gene was markedly decreased in many human immortalized and tumor-derived cell lines. To further investigate the function of the REIC/Dkk-3 gene in vivo, the gene expression was quantified in 57 surgically-resected non-small cell lung cancer (NSCLC) tissues and their adjacent normal lung tissues by real-time quantitative PCR analysis based on TaqMan methodology. The REIC/Dkk-3 mRNA level was significantly lower in NSCLC tissues than in normal lung tissues. Reduced expression of REIC/Dkk-3 in NSCLC was observed in 36 (63%) of the 57 tumors. Reduced expression of REIC/Dkk-3 was frequently observed in poorly differentiated adenocarcinoma and squamous cell carcinoma. These results indicate that reduced expression of REIC/Dkk-3 may be correlated with rapid cell proliferation in human NSCLC.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Thymidine phosphorylase expression is useful in selecting adjuvant chemotherapy for stage III gastric cancer.

Thymidine phosphorylase (TP) is an enzyme which converts doxifluridine (5'-DFUR) to 5-fluorouracil (5-FU). To assess whether TP expression is useful for selecting adjuvant chemotherapy in advanced gastric cancer, we compared effects of oral 5'-DFUR and 5-FU and assessed correlation between drug efficacy and TP expression level. We examined TP expression in 286 patients. TP expression was assessed with immunohistochemical staining. When we compared prognosis in two chemotherapy groups with high TP expression, better survival was observed in 5'-DFUR than in 5-FU group (p=0.0413). Especially in stage III, patients with high TP had better survival in 5'-DFUR than in 5-FU group.

Adult↗
PubMed2001

[Blood concentrations and side effects of tacrolimus in a living renal transplantation].

In a living renal transplantation, the recipients are administered an immunosuppressive agent preoperatively. The drug exhibits a high incidence of side effects of special note. We examined the side effects of tacrolimus to evaluate the postoperative management of living renal transplantation. Hypertension, hyperglycemia, tachycardia and chest pain were found as the side effects. The blood concentration should be measured frequently to maintain the effective blood concentration and to prevent the side effect.

Adult↗
PubMed2001

[Bronchiolitis obliterans organizing pneumonia after adjuvant thoracic radiotherapy for breast cancer: a case report].

We report a case of recurrent cough and migratory pulmonary infiltrates in a 55-year-old woman after adjuvant thoracic radiotherapy for breast cancer. The pulmonary infiltrates were initially limited to the area adjacent to the irradiated breast, but later migrated to the opposite lung. The diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP) was made using a transbronchial biopsy, which disclosed intraluminal fibrosis in the distal airspace, together with a radiographic appearance typical of BOOP. This case was assumed to be in a series of reported cases of BOOP primed by radiotherapy.

Breast Neoplasms↗
PubMed2001

Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum.

Multiple pathways of angiotensin (Ang) I conversion and their functional role in the canine penile corpus cavernosum were investigated. Biochemical analysis revealed high activities of angiotensin-converting enzyme (ACE) (6.9 +/- 1.7 mU/mg of protein, mean +/- S.E.M., n = 8) and chymase-like enzyme (4.0 +/- 1.4 mU/mg of protein). Functional recording of isometric tension showed that Ang I (3 x 10(-7) M) induced a tension of 0.17 +/- 0.05 g (n = 5), which was reduced to about 60% by pretreatment with an ACE inhibitor, lisinopril (10(-6) M), and almost completely blocked by lisinopril in combination with a chymase inhibitor, chymostatin (10(-4) M). Binding sites for ACE and Ang II receptors were studied by in vitro autoradiography using 125I-351A and 125I-[Sar1, Ile8]Ang II as ligands, respectively. Dense binding of ACE appeared in the endothelial layer of the corpus cavernosum penis, and Ang II receptors were localized in the trabecular smooth muscle layer. An AT1 receptor antagonist, CV-11974 (10(-6) M), markedly displaced 125I-[Sar1, Ile8]Ang II bindings, indicating that the corpus cavernosum penis contains AT1 receptors exclusively. Immunohistochemical studies demonstrated ACE in the endothelium of the corpus cavernosum penis. Mast cells that produce chymase were present mainly in the cavernosal area. These results demonstrate that chymase, in addition to ACE, is involved in the contraction of canine penile corpus cavernosum through local Ang II formation.

Angiotensin I↗
PubMed2001

[A case of silicosis with MPO-ANCA-associated glomerulonephritis and alveolar hemorrhage].

A 63-year-old man was referred to our hospital for rapid deterioration of his renal function. He had worked as a metal founder for more than 40 years, and had been diagnosed as having silicosis. Laboratory data on admission showed severe anemia, thrombocytopenia, and end-stage renal failure (BUN 88.8 mg/dl, serum creatinine 9.0 mg/dl). Myeloperoxidase anti-neutrophil cytoplasmic antibody(MPO-ANCA) was also detected in his sera. On the next day after admission, he complained of sudden dyspnea and hemoptysis. Mechanical ventilation with pure oxygen was insufficient to improve hypoxia without concomitant use of percutaneous cardio-pulmonary support(PCPS) and continuous hemofiltration(CHF). We diagnosed his condition as MPO-ANCA-associated rapidly progressive glomerulonephritis with diffuse alveolar hemorrhage. Treatment with plasmapheresis, pulse methylprednisolone and pulse cyclophosphamide effectively improved his hemoptysis as well as chest X-ray findings and blood gas analysis. However on his later clinical course, he was complicated with superimposed complex infection and passed away. Autopsy findings showed crescentic glomerulonephritis in the kidneys and silica nodules in the lungs. Recently it has been postulated that some relationship exists between ANCA-associated(especially MPO-ANCA-associated) glomerulonephritis and silica exposure. The reported cases of glomerulonephritis in the patients with silica exposure showed a rapidly progressive clinical course and pauci-immune necrotizing crescentic glomerulonephritis in their histology. Gregorini et al. reported that 12 of 37 (32%) male patients with RPGN had either silicosis or significant silica exposure, and 7 of 8 patients examined were ANCA-positive(6 of 7 were MPO-ANCA-positive). Therefore silica seems to cause glomerulonephritis by disrupting the immune response. Including this case mentioned above, we have experienced 10 cases of MPO-ANCA-associated glomerulonephritis, at least 3 cases out of which had suffered from silicosis in the past(30%). These results indicate that silicosis should be considered a relevant pathogen of MPO-ANCA-associated glomerulonephritis beyond the race.

Antibodies, Antineutrophil Cytoplasmic↗