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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 253 records · Page 14Linked to original sources
PubMed1999

[Pathophysiological roles of chymase and effects of chymase inhibitor].

Human chymase forms angiotenin (ANG) I to ANG II, whereas the roles of ANG II generated by chymase and the effects of chymase inhibitors have been unclear. On the other hand, rat chymase could not convert ANG I to ANG II. In isolated rat arteries, the ANG I-induced vascular contraction was completely suppressed by angiotensin-converting enzyme (ACE) inhibitor only. However, 30% of ANG I-induced vascular contraction in isolated human arteries was suppressed by an ACE inhibitor, but the remainder was blocked by chymostatin. In hamster hypertensive models, ANG II formation by ACE, but not by chymase, in vascular tissues plays an important role in maintaining hypertension. ANG II formation also induces vascular remodeling such as neointima formation. After balloon injury of vessels in dog, chymase and ACE activities were significantly increased in the injured vessels. In this model, an ANG II receptor antagonist was effective in preventing neointimal formation after balloon injury of vessels in dog, but an ACE inhibitor was ineffective. In dog grafted veins, the activities of chymase and ACEmin the grafted vein were significantly increased 15- and 2-fold, respectively, compared with those in the symmetrical veins. The intimal area of the grafted vein was reduced by a chymase inhibitor. Therefore, chymase-dependent ANG II formation plays an important role in the proliferative response, and chymase inhibitors may appear useful for preventing vascular proliferation.

Angiotensin I↗
PubMed1999

Inhibition of the angiotensin II Type 1 receptor by TCV-116: quantitation by in vitro autoradiography.

Inhibition of angiotensin (Ang) II type 1 (AT1) receptors in various target tissues of adult Sprague-Dawley rats was studied after single oral administration of TCV-116. The effects of TCV-116 on Ang II-receptor binding were assessed by quantitative in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand. Four hours after the administration of TCV-116 (1 mg/kg), Ang II-receptor binding was markedly inhibited in the kidney (20% of control), adrenal cortex (27%), thoracic aorta (57%), heart (55%) and testis (76%) where AT1 receptors predominate. In the brain, orally administered TCV-116 produced a significant inhibition of binding both to the circumventricular organs (38%), which are devoid of the blood-brain barrier (BBB), and to the discrete regions within the BBB such as the paraventricular hypothalamic nucleus (48%), nucleus of the solitary tract (60%). Twenty-four hours after the administration, Ang II-receptor binding had partly recovered to approximately 50-85% of control levels. In contrast, throughout the experimental period, Ang II-receptor binding was little affected in sites where Ang II type 2 (AT2) receptors predominate such as the adrenal medulla and the nucleus of the inferior olive. These data indicate that orally administered TCV-116 specifically binds to AT1 receptors both in peripheral tissues and the central nervous system.

Administration, Oral↗
PubMed1999

Angiotensin II type 1 receptor antagonist, TCV-116, prevents neointima formation in injured arteries in the dog.

We investigated the effect of an angiotensin (Ang) II antagonist, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy- 1- [[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]- 1H-benzimidazole-7-carboxylate (TCV-116), on neointima formation in dog artery injured by a balloon catheter. Dogs were orally treated with 10 mg/kg TCV-116 or placebo twice a day for 5 weeks. After treatment with these drugs for 1 week, the right carotid artery was injured by a balloon catheter. The left carotid artery was regarded as the control. In the group treated with placebo, neointima formation in the injured arteries was observed. The activities of angiotensin converting enzyme (ACE) and chymase in the injured carotid arteries were increased 2.56- and 3.26-fold compared with those in the non-injured arteries, respectively. The neointimal area in dogs treated with placebo and TCV-116 were 0.51 +/-0.07 and 0.21 +/-0.07 mm2, respectively, and this difference was significant. In conclusion, an Ang II antagonist, TCV-116, prevented neointima formation by blocking the action of Ang II generated by both ACE and chymase in the injured arteries.

Angiotensin Receptor Antagonists↗
PubMed1999

Effects of a lipoxygenase inhibitor, panaxynol, on vascular contraction induced by angiotensin II.

We investigated whether a lipoxygenase inhibitor, panaxynol, affected the vascular contraction induced by angiotensin (Ang) II and the mean arterial pressure in spontaneously hypertensive rats (SHR). Panaxynol suppressed dose-dependently the contractile responses induced by 30 nM Ang II in isolated intact and endothelial cell-denuded aorta in the hamster. IC50 values in the intact and endothelial cell-denuded aorta were 23 and 20 microM, respectively. In SHR, the mean arterial pressure after injection of 30 and 60 mg/kg panaxynol was reduced, and the maximum hypotensive values were 23 and 48 mmHg, respectively. Thus, lipoxygenase products may affect the renin-angiotensin system.

Alkynes↗
PubMed1999

Inhibition of human chymase by suramin.

Chymase is a chymotrypsin-like protease localized in mast cells in complexes with heparin. In the present study, we demonstrated that suramin, a hexasulfonated naphthylurea used as an anti-cancer drug, inhibits the activity of purified human chymase in vitro. The inhibition was ionic-strength-dependent. It was observed that suramin competed with heparin-Sepharose gel for binding to chymase and the inhibition of chymase activity by suramin was partially impaired by heparin. Our results show that suramin may become a prototype of a new type of chymase inhibitor because of its unique character.

Antineoplastic Agents↗
PubMed1999

A preliminary study for clinical pharmacokinetics of oral fluorine anticancer medicines using the commercial MRI system 19F-MRS.

These preliminary studies of dynamic natural abundance 19F-magnetic resonance spectroscopy (19F-MRS) on 5-FU based medicines were performed in the human liver using commercial 1.5 T MRI equipment. A single tuned, custom-made circular shape surface coil with a diameter of 15 cm operating at 60 MHz was used for the 19F-MRS study. Localized proton shimming with a whole body coil was performed with adequate volume to include the observing area of the surface coil, and the line width of the water signal was less than 40 Hz. Very different spectroscopic appearance patterns of 5-FU were observed. We examined whether the pharmacokinetics in the liver of orally administered 1-hexylcarbamoyl-5-fluorouracil (HCFU) differ from those of orally administered 5'-deoxy-5-fluorouridine (5'-DFUR). This preliminary study suggested the 19F-MRS technique could be a useful method of evaluating in vivo the metabolism of 5-FU based medicines.

Administration, Oral↗
PubMed1999

[Serum leptin level among non-obese students: relationship to body fat, blood pressure, serum lipids, physical activity, and eating habits].

Leptin, a product of the ob gene, is thought to play a key role in the regulation of adiposity. However, it is unclear in humans as to whether or not leptin influences the blood pressure, serum lipids, physical activity level, or eating behavior in relation to obesity. Recent reports have indicated both gender-based differences in the leptin levels and a correlation of the percentage of body fat with leptin levels has been observed among obese subjects. As far as we know, these relationships among non-obese young adults have yet to be studied. Therefore, the serum leptin concentrations among 107 non-obese students (72 males and 35 females) were measured by a radioimmunoassay(RIA). Fasting leptin levels ranging between 1.2 and 23.4 ng/mL were observed in all subjects, and the levels among females were 2.6 times higher than in males (7.64 vs 2.95 ng/mL; p < 0.001). A close correlation was observed regarding the log-transformed leptin levels with the percentage of body fat as determined by the bioelectrical impedance analysis method(r = 0.734, p < 0.001 in males and r = 0.579, p < 0.001 in females). In conclusion, these data thus suggest the serum leptin levels among non-obese students show significant gender-based differences while, in addition, the leptin levels also correlate positively with the percentage of body fat. However, it remains unclear as to whether or not the leptin levels are independently related to the blood pressure, serum lipids, physical activity level (sports activity and leisure-time activity), and eating behavior (eating breakfast, mid-day snacking and nighttime snacking).

Adipose Tissue↗
PubMed1999

Antiatherosclerotic effect of alacepril, an angiotensin-converting enzyme inhibitor, in monkeys fed a high-cholesterol diet.

We investigated the effects of 6 months' treatment with the angiotensin-converting enzyme (ACE) inhibitor alacepril, given in low (100 mg/kg/d, p.o.) and high (200 mg/kg/d, p.o.) doses, on the development of atherosclerotic lesions in the aorta of monkeys fed a high-cholesterol diet for 6 mo. Mean blood pressures in the normal-diet group, high-cholesterol-diet group, and high-cholesterol-diet group treated with a low dose of alacepril were very similar, while that in the high-cholesterol-diet group treated with a high dose of alacepril was significantly reduced. The level of low-density lipoprotein in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the levels in the alacepril groups were significantly lower than those in the high-cholesterol-diet group. Atherosclerotic lesions in the normal- and high-cholesterol-diet groups were 13.2 +/- 0.34% and 64.1 +/- 10.48%, respectively, and those in the groups treated with low and high doses of alacepril were 32.3 +/- 13.2% and 16.0 +/- 1.57%, respectively. Angiotensin-converting enzyme (ACE) activity in the thoracic aorta in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the ACE activities in the alacepril groups were lower than that in the high-cholesterol-diet group. We conclude that alacepril prevents the development of atherosclerosis by reducing vascular ACE activity in monkeys given a high-cholesterol diet.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Unresponsiveness to glibenclamide during chronic treatment induced by reduction of ATP-sensitive K+ channel activity.

The insulin response to the sulfonylurea glibenclamide was markedly impaired in pancreatic beta-cell line MIN6 cells with chronic glibenclamide treatment (MIN6-Glib). The intracellular calcium concentration increased only slightly in response to glibenclamide in MIN6-Glib. While the properties of the voltage-dependent calcium channels were not altered, the conductance of the K(ATP) channels, the primary target of glibenclamide, was significantly reduced in MIN6-Glib. The ATP-sensitive K+ (K(ATP)) channels in MIN6 cells comprise inwardly rectifying K+ channel member Kir6.2 subunits and sulfonylurea receptor (SUR) 1 subunits. MIN6 cells have both high- and low-affinity binding sites for glibenclamide. The binding affinities at these two sites were unchanged, but the maximum binding capacities at both sites were similarly increased by chronic glibenclamide treatment. Both SUR1 and Kir6.2 mRNA levels were not altered, but SUR1 protein was rather increased in MIN6-Glib. In addition, electron microscopic examination revealed a majority of the SUR1 to be present in a cluster near the plasma membrane in control MIN6, while it tends to be distributed in the cytoplasm in MIN6-Glib. These data suggest that chronic glibenclamide treatment causes the defect in acute glibenclamide-induced insulin secretion by reducing the number of functional K(ATP) channels on the plasma membrane of the beta-cells.

ATP-Binding Cassette Transporters↗
PubMed1999

Maintenance of near-diploid karyotype of PA-1 human ovarian teratocarcinoma cells due to death of polyploid cells by chromosome fragmentation/pulverization.

Chromosome instability (polyploidy or aneuploidy) is one of the characteristics of malignant tumors. Human teratocarcinoma cell line PA-1, which was established more than 10 years ago, consists of a majority of near-diploid cells and a minority of polyploid cells, indicating that it is karyologically very stable. In the present study we investigated this genomic stability from the view point of cytogenetics. Cleavages and breaks in the chromosome were found in the metaphase of PA-1 polyploid cells, accompanied by the formation of polynucleosomal DNA fragments. These findings were absent in the near-diploid cells. In addition, polyploid cells did not show colony-formation ability by in situ analysis of cytogenetics in each colony. Thus, the maintenance of the near-diploid karyotype in PA-1 cells may be due to a blockage in the M-phase of the polyploid cells by functional mitotic checkpoints, if any, leading to cell death due to inability to enter the next cell cycle.

Chromosome Banding↗
PubMed1999

Cytogenetic characteristics and p53 gene status of human teratocarcinoma PA-1 cells in 407-445 passages.

To study why the human teratocarcinoma cell line PA-1 maintains a stable near-diploid karyotype even after it has been cultured for more than twenty years, p53 gene status of the cell line in 407-445 passages were investigated in detail by DNA sequence analysis and a yeast function status assay. Direct sequence analysis of RT-PCR products showed both wild and mutated bands (p53 codon 239 mutation). Consistent with the above results, the functional assay showed that one allele of the p53 gene was active (wild), while the other was inactive (mutant). In addition, the PA-1 cells expressed the p21 protein to a lesser extent than normal human fibroblasts. Though many lines of evidence have shown that mutant p53 works dominant-negatively, our results suggest that mutation in a p53 allele alone can not induce cytogenetic instability.

Aneuploidy↗
PubMed1999

Comparative genomic hybridization defines frequent loss on 16p in human anaplastic thyroid carcinoma.

Anaplastic thyroid cancer (ATC) is one of the malignant tumors with the poor prognosis that is thought to arise from well-differentiated thyroid cancer (DTC). To investigate the molecular mechanism of ATC, we studied genomic alterations of eight ATC cell lines and three DTC cell lines by means of the comparative genomic hybridization (CGH) method. Loss of 16p was observed in five of eight ATC cell lines (62. 5%), but none of the three DTC cell lines showed loss of this chromosome arm. It is notable that loss of 18q [7/8 of ATC (87.5%), 2/3 of DTC (67%)] and gain of 20q [5/8 of ATC (62.5%), 3/3 of DTC (100%)] were frequently seen in both histologic types. Our results suggest that there is a gene in 16p that is closely associated with transformation from well-differentiated thyroid cancer to anaplastic cancer.

Carcinoma↗
PubMed1999

[Role of angiotensin II-forming enzymes, angiotensin-converting enzyme and chymase].

Angiotensin (Ang) II plays a crucial role in regulation of blood pressure and proliferation of vascular tissues. Recent studies have demonstrated that the AngII-forming enzymes, ACE and chymase, are observed in heart and vascular tissues. In isolated human arteries, chymase predominantly converted Ang I to AngII rather than ACE. In hypertensive models, AngII formation by ACE in vascular tissues plays an important role in maintaining hypertension, while that by chymase hardly does. Chymase-dependent AngII formation induces vascular diseases such as neointima formation after balloon injury. AngII receptor antagonists block AngII formation by chymase in addition to ACE and may be useful for cardiovascular diseases rather than ACE inhibitors.

Animals↗
PubMed1999

[Morphological changes in rabbit corneal endothelium after surgical injuries].

PURPOSE: To understand the responses of the corneal endothelium to different types of surgery, we chronologically investigated the morphologic changes in the endothelial cells. METHODS: We did a mechanical incision, epithelial ablation, and excimer laser radiation on rabbit corneas and observed the morphologic changes in the endothelial cells for up to 2 weeks after surgery under a light microscope and an electron microscope. RESULTS: Although we observed enlarged intercellular spaces between neighboring endothelial cells, intercellular adhesion kept the cells tightly joined near their apexes immediately after each procedure. No signs of endothelial cell degeneration were observed after the procedures, but we did observe many Golgi apparati, rough-surfaced endoplasmic reticula, and secreted granules, indicating that the cells had been activated. After each procedure, the intercellular junctions and spaces required different amounts of time to return to normal. CONCLUSIONS: These results suggest that the different kinds of surgical injuries affected the corneal endothelium but that the changes were reversible.

Animals↗
PubMed1999

Thermal regulation in the heat during exercise after caffeine and ephedrine ingestion.

BACKGROUND: Ingesting a combination of caffeine and ephedrine (C+E) has been shown to raise metabolic heat production and body temperature. This side effect of C+E ingestion may be positive during a cold stress scenario, however, during heat stress it could prove to be detrimental. Thus, the purpose of this study was to clarify the effect of C+E ingestion on body temperature regulation during moderate exercise in a hot dry environment. METHODS: Ten, healthy, non heat acclimated, males exercised at 50% VO2peak in a 40 degrees C and 30% RH environment until rectal temperature reached 39.3 degrees C; heart rate (HR) remained at 95% of peak value or greater for 3 min, dizziness or nausea precluded further exercise, or 3 h had elapsed. They did this four times at weekly intervals: familiarization (Fam), control (Cont), placebo, and C+E (5 mg . kg(-1) caffeine + 1 mg . kg(-1) ephedrine) trials. The Fam and Cont treatments were done first and sequentially while the placebo and C+E treatments were balanced and double-blind. Tolerance times, mean skin temperature (Tsk), rectal temperature (Tre), Vo2, Vco2, VE, sweat rate (SR), HR, and sensation of thermal comfort were measured. RESULTS: Tolerance times (mean+/-SD in minutes) were similar for the placebo (120.0+/-28.4) and C+E (121.3+/-33.9) trials and both times were significantly longer than Cont (106.6+/-24.0) trial. C+E did not affect Tsk, initial TrC, delta Tre, SR or the sensation of thermal comfort. VO2 and VF, were significantly increased by C+E. HR was elevated by C+E compared with the other trials, but only during the initial 20 min of exercise. CONCLUSION: Although the metabolic rate was slightly increased with C+E treatment, it was sufficiently offset by increased heat loss mechanisms so that internal body temperature was not increased during moderate exercise in a hot, dry environment.

Adult↗
PubMed1999

[A case report: effective trans-arterial neoadjuvant chemotherapy with docetaxel for a local advanced breast cancer patient].

Recently, there have been some reports about the effectiveness of docetaxel for breast cancer patients who had polychemotherapy previously in vein. We report here a case of a 47-year-old woman, who had been diagnosed as local advanced breast cancer. She was given trans-arterial chemotherapy with docetaxel after four series of CEF (cyclophosphamide, epirubicin, fluorouracil) therapy resulted in PD (progressive disease). Local disease was successfully controlled, and she could undergo standard radical mastectomy.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Peritoneal dialysis--associated peritonitis caused by gram-negative bacteria: characteristics similar to spontaneous bacterial peritonitis?

The aim of the study was to investigate the characteristics of PD-related peritonitis caused by gram-negative bacteria (GNP). We retrospectively studied the medical records of 164 patients (114 males, 50 females; mean age 46 +/- 15 years) who continued PD beyond 5 months between 1984 and 1998. The average observation time was 40 +/- 28 months (total of 6609 patient-months). A total of 166 episodes of peritonitis occurred during that time (mean incidence: 1 episode/40 patient-months). Of these, 35 were GNPs, and GNP incidence stayed almost constant over time. Most GNP patients (63%) recovered without complication with an average of 14 days' antibiotic treatment. In only 4 cases was PD abandoned. Clinical features of GNP were similar to those of spontaneous bacterial peritonitis (SBP). The unchanged incidence of GNP over time with advanced connection devices suggests that there are important mechanisms promoting micro-organisms of endogenous origin into the peritoneal cavity in PD patients.

Adolescent↗