Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 181 records · Page 10Linked to original sources

PubMed2000

Normalized spleen/liver ratios on 111In-labelled platelet scintigraphy to predict the outcome of partial splenic embolization in patients with idiopathic thrombocytopenic purpura.

In this study, we examined the use of 111In-labelled platelet imaging to predict the outcome of partial splenic embolization (PSE) in patients with idiopathic thrombocytopenic purpura (ITP). Thirty-eight patients with a clinical diagnosis of ITP underwent 111In-labelled platelet scintigraphy. Twenty-four patients with intractable ITP underwent PSE after 111In-labelled platelet scintigraphy. The conventional spleen/liver ratio at 1 h and 192 h and the normalized spleen/liver ratio [(spleen uptake at 192 h/liver uptake at 192 h)/(spleen uptake at 1 h/liver uptake at 1 h)] were compared between responders and non-responders to PSE. Patients with ITP showed a significant reduction in platelet counts, increased platelet associated IgG, decreased platelet survival, and an increased conventional spleen/liver ratio at 192 h. No significant difference was found between patients who had and who had not undergone previous medical treatment. A significant difference was observed in the mean conventional spleen/liver ratio at 192 h between responders and non-responders, but there was substantial overlap among individuals. The mean normalized spleen/liver ratio was significantly higher in responders than non-responders; there was less overlap between the two groups with the normalized spleen/liver ratio than the conventional spleen/liver ratio. The therapeutic outcome of PSE is predicted more accurately using a normalized spleen/liver uptake ratio of 111In-labelled platelets in patients with idiopathic thrombocytopenic purpura than a conventional splenic/hepatic uptake ratio on delayed images.

Adult↗

PubMed2000

Implication of NF-kappaB in Helicobacter pylori-associated gastritis.

OBJECTIVE: Transcription factor NF-kappaB plays a pivotal role in inflammatory responses by up-regulating mRNA expression of bioactive molecules such as chemokines and adhesion molecules. The present study was designed to elucidate the implication of NF-kappaB in Helicobacter pylori-associated gastritis (HAG). METHODS: We examined 41 patients with HAG and 18 H. pylori-negative control subjects. Expression of activated NF-kappaB was studied in situ by immunohistochemistry using alpha-p65 mouse monoclonal antibody (alpha-p65 mAb), which recognizes activated NF-kappaB. To identify the cell types in which NF-kappaB was activated, we performed immunohistochemical analysis using antibodies against vascular endothelial cells, macrophages, and B and T lymphocytes. We also examined the colocalization of activated NF-kappaB with the of intercellular expression adhesion molecule-1 (ICAM-1) on endothelial cells. We measured the levels of NF-kappaB-dependent chemokines including interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein-1alpha (MIP-1alpha) in antral mucosa by ELISA (ELISA). RESULTS: Activated NF-kappaB was detected in the nuclei of epithelial cells in antral mucosa, especially of patients with HAG. NF-kappaB positivity index (NF-kappaB PI), representing the percentages of epithelial cells with positive nuclear staining for activated NF-kappaB, was significantly higher in patients with HAG than in H. pylori-negative controls. NF-kappaB PI correlated significantly with histological scores of gastritis. Moreover, activated NF-kappaB was identified in the nuclei of vascular endothelial cells, macrophages, and B lymphocytes within the lamina propria in HAG. Colocalization of activated NF-kappaB with ICAM-1 expression in the same endothelial cells was demonstrated. The IL-8 levels significantly correlated with the NF-kappaB PI. CONCLUSIONS: In addition to epithelial cells, macrophages, vascular endothelial cells, and B lymphocytes contained activated NF-kappaB. In these cells, activated NF-kappaB may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules.

Adult↗

PubMed2000

Beneficial effects of prostaglandin E(1) incorporated in lipid microspheres on liver injury and regeneration after 90% partial hepatectomy in rats.

The aim of this study was to assess how the administration of prostaglandin E(1) incorporated in lipid microspheres (Lipo PGE(1)) affects liver injury and regeneration after massive hepatectomy in rats. Two hundred and eight male Wistar rats underwent 90% partial hepatectomy. Lipo PGE(1) of 1, 10 or 30 microg/kg were administered intraperitoneally at 6 h prior to and 0 and 6 h after hepatectomy. Postoperative increases in serum GOT, total bilirubin, IL-6 and plasma endotoxin levels were significantly suppressed by Lipo PGE(1). The depressed phagocytic index and arterial ketone body ratio and hepatic DNA synthesis after 90% partial hepatectomy were significantly enhanced by Lipo PGE(1), which resulted in the improvement of survival. Lipo PGE(1) might bring about a protective effect on liver injury and an enhancement of liver regeneration after massive hepatectomy.

Alprostadil↗

PubMed2000

Secretion of extracellular matrix (fibronectin), growth factor (transforming growth factor beta) and protease (cathepsin D) by hepatoma cells.

We investigated facilitation of invasion by growth factors and chemotactic factors in tumor cell lines, particularly hepatocellular carcinoma. Hepatoma cells (PLC/PRF/5 and Hep G2) showed strong chemotaxis toward their respective conditioned media while metastatic pancreatic cancer cells (SU.86.86) and colon cancer cells (LS 174T) did not migrate toward their respective conditioned media. Based on immunoblotting, PLC/PRF/5 cells secrete fibronectin (an extracellular matrix constituent), transforming growth factor-beta (TGFbeta; a growth factor), and cathepsin D (a protease). Fibronectin induced a migratory response in PLC/PRF/5 cells, and anti-fibronectin antibody abolished the migratory response of these cells to their conditioned medium. Anti-integrin-beta(1) antibody also impeded migration of these cells toward conditioned medium. Polyclonal anti-TGFbeta antibody and protease inhibitors (alpha(2)-macroglobulin and leupeptin) added to culture media-modulated secretion of fibronectin by PLC/PRF/5 cells. Although exogenous TGFbeta suppressed SU.86.86 cells, it enhanced PLC/PRF/5 cell adhesion to substrate, increasing viable cell numbers. These actions indicate that hepatocellular carcinoma may possess a forceful autocrine mechanism enabling cells to survive and proliferate under cirrhotic conditions.

Antibodies, Neoplasm↗

PubMed2000

Effects of perioperative protease inhibitor on inflammatory cytokines and acute-phase proteins in patients with hepatic resection.

AIM: The objective of this study was to examine the effects of perioperative administration of ulinastatin, or urinary trypsin inhibitor (UTI), on inflammatory cytokines and acute-phase proteins induced by inflammatory cytokines in patients who had undergone hepatic resection. METHOD: Twenty patients admitted to the hospital for hepatic resection were equally randomized to one of two groups: the UTI group, those who were administered perioperative UTI, and the control group. RESULTS: The UTI group had no adverse effects from using UTI. Production of serum interleukin-6 (IL-6) tended to be attenuated in the UTI group when compared with the control group. Moreover, the UTI group had significantly decreased positive acute-phase C-reactive protein (p < 0.05) and significantly increased negative acute-phase protein prealbumin and retinol-binding protein (p < 0.05). Serum IL-6 levels significantly correlated with serum C-reactive protein levels on postoperative day 1 (r = 0.70, p < 0.01). CONCLUSION: These results suggest that perioperative administration of UTI might deserve further assessment for use in modulating acute-phase responses without adverse effects in patients who have undergone hepatic resection.

Acute-Phase Proteins↗

PubMed2000

Bioavailability assessment of disopyramide using pharmacokinetic-pharmacodynamic (PK-PD) modeling in the rat.

The relationship between the serum concentration and the pharmacological effect of disopyramide was investigated quantitatively to estimate the extent of its oral bioavailability (EBA(p.o.) and to evaluate the drug interaction with miconazole, a CYP3A4 inhibitor. An integrated pharmacokinetic-pharmacodynamic (PK-PD) model was used to describe the relationship between the serum concentrations and changes in QT interval (pharmacological data) of disopyramide after intra-vascular infusion for 15 min (i.v. short-term infusion) to rats. A two-compartment model was applied to the pharmacokinetics of disopyramide. The pharmacological data after short-term infusion were well explained using a PK-PD link model. To validate the present PK-PD model. disopyramide was administered intra-vascularly in separate experiments, and the doses were predicted only from the pharmacological data. The model predicted doses were identical to the actual doses, regardless of the dosing rates. This result indicates that the PK-PD model used in the present study is appropriate, and that the relationship between the serum concentrations and changes in QT intervals is independent of the dosing (input) rate. When miconazole was co-administered orally 1 h before disopyramide infusion, the serum disopyramide concentrations were significantly higher than that following disopyramide alone. The raised serum concentrations under miconazole co-administration were well explained by nonlinear elimination clearance. The pharmacological effects of disopyramide under miconazole co-administration, were also greater than those following disopyramide alone. The results of the PK-PD analysis indicated that the enhanced pharmacological response under miconazole co-administration was simply caused by a pharmacokinetic change. The EBA(p.o.) values estimated from the pharmacological effects predicted the observed values reasonably well. In conclusion, we demonstrated following: (1) the pharmacological effect after intra-vascular administration of disopyramide is related quantitatively to the serum concentrations using a PK-PD model; (2) miconazole affects only the elimination clearance of disopyramide to enhance the pharmacological effect; (3) the EBA of disopyramide can estimated reasonably only well from the pharmacological data using the PK-PD model; (4) there is no dosing-rate-dependent or dosing-route-dependent pharmacological effect of disopyramide.

Algorithms↗

PubMed2000

Bioavailability assessment of arginine-vasopressin (AVP) using pharmacokinetic-pharmacodynamic (PK-PD) modeling in the rat.

A novel method of assessing the extent of oral bioavailability of arginine-vasopressin (AVP) from pharmacological data was presented. After intravascular administration (i.v. bolus or short-term infusion) of AVP to rats, the relationship between blood concentrations and its effect on both mean arterial pressure (hemodynamic effect) and urinary sodium concentration (anti-diuretic effect) was described on the basis of an integrated pharmacokinetic-pharmacodynamic (PK-PD) model. A direct model was used for the hemodynamic response, while an indirect response model, rather than a hypothetical link model was used for the anti-diuretic response. A sigmoid Emax model was applied to describe the drug-receptor interaction. Pharmacological responses after intravascular administration of AVP were reasonably described by the PK-PD model. However, PD parameters estimated by the PK-PD analysis suggested that apparent receptor affinity rather than efficacy in i.v. bolus study was significantly higher than that in the short-term infusion study. This fact indicated that PK-PD relationship was influenced by the intravascular input rate of AVP. We then investigated the relationship between plasma concentration and amount of AVP bound to the V2 receptors in the kidney. The result indicated that the amount of AVP bound to the receptors after i.v. bolus injection was always greater than that after short-term infusion. Since the PK-PD relationship after oral administration was almost identical with that after short-term infusion, the PK-PD model obtained in the short-term infusion study was used to assess the extent of oral bioavailability (EBAPp.o.). The EBAp.o. values, estimated from pharmacological effects (hemodynamic effect and anti-diuretic effect) after oral administration of 5 microg/kg of AVP were 0.68% to 0.93% and were almost identical with the actual EBAPp.o. value (0.81%). From these results, we concluded that oral bioavailability of AVP was reasonably predicted by the PK-PD model, provided that appropriate pharmacological effects and appropriate intravascular dosing rate as a reference formulation are available. The method may be an alternative to methods based on plasma concentrations, when drug concentration cannot be measured and when appropriate pharmacological data are available.

Administration, Oral↗

PubMed2000

Characterization of recombinant human chymase expressed in Escherichia coli.

We compared recombinant human chymase expressed in Escherichia coli with human chymase purified from vascular tissues. The recombinant chymase, the structure of which was NH2-enterokinase cleavage site-chymase-COOH, was expressed in Escherichia coli and then was solubilized and renatured. The protein did not have a chymase activity, but gained this activity after the cleavage of the N-terminal site by enterokinase. The enzyme was purified by heparin affinity and gel filtration columns. The N-terminal sequence of the protein was identical to the sequence for human chymase. The molecular weights of the recombinant chymase and chymase purified from human vascular tissues were 26 and 30 kDa, respectively, and the 4 kDa difference was thought to be due to the presence or absence of glycan. The optimum pH of the recombinant enzyme activity was between 7.5 and 9.0. The activity of the recombinant enzyme was inhibited by chymostatin, soybean trypsin inhibitor and phenylmethylsulfonyl fluoride, but not by ethylenediaminetetraacetic acid and aprotinin. This enzyme cleaved specifically the Phe8-His9 bond of angiotensin (Ang) I to form Ang II and that of big endothelin (ET)-1 to form ET-1-(1-31). These findings demonstrated that the enzymatic characteristics of the recombinant enzyme were identical to that of native human chymase.

Amino Acid Sequence↗

PubMed2000

Characteristics of monkey tryptase purified from cheek pouch vascular tissues.

Tryptase purified from rat and dog tissues has been reported, although the characteristics of these enzymes are different from human tryptase. For pathophysiological studies of human tryptase, studies on species that have a similar tryptase to humans is needed. In this study, we purified monkey tryptase from cheek pouch vascular tissues using heparin affinity and gel filtration columns. The monkey tryptase, which had a molecular weight of 130 kDa by gel filtration, consisted of a tetramer of 33 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The N-terminal sequence showed high homology with tryptases from other species. The optimum pH and temperature were 7.5-9.0 and 25-40 degrees C, respectively. The enzyme was labile in high-KCl buffer, and the optimum KCl concentration was 0.1 M. The enzyme activity was completely inhibited by diisopropyl phosphorofluoridate and leupeptin but not by soybean trypsin inhibitor and alpha-antitrypsin. The enzyme hydrolyzed vasoactive intestinal peptide but did not affect angiotensin I, somatostatin and bradykinin. In the present study, we first isolated monkey tryptase from cheek pouch vascular tissues and showed that the characteristics of monkey tryptase are very similar to those of human tryptase.

Animals↗

PubMed2000

The functional ratio of chymase and angiotensin converting enzyme in angiotensin I-induced vascular contraction in monkeys, dogs and rats.

Recently, a chymase-dependent angiotensin (Ang) II-forming pathway was found in human cardiovascular tissues, and the significance of this pathway in the pathogenesis of some cardiovascular diseases was suggested. The present study examined the ratio of angiotensin converting enzyme (ACE) to chymase-dependent Ang II formation in various isolated vessels from monkeys, dogs and rats. In all of the examined vessels, the addition of KCl at a concentration of 50 mM could induce a maximal contraction. Except for monkey coronary artery and rat renal and femoral artery, the addition of Ang I could induce transitory contractions, whereas the force of contractions in these vessels was quite different. The sensitivity to Ang II in these vessels was similar to that for Ang I. In monkey gastroepiploic and mesenteric arteries, about 70% of the Ang I-induced contraction was suppressed by chymase inhibition, while it was suppressed about 50% in monkey renal, femoral and carotid arteries. In dog renal arteries, about 65% of the Ang I-induced contraction was suppressed by chymase inhibition, while it was suppressed by about 30% in other dog arteries. In contrast, in all rat arteries, Ang I-induced contractions were completely suppressed by treatment with ACE inhibitor alone. We concluded that regional differences in the response to Ang I exist in vascular tissues, and the ratio of ACE- to chymase-dependent Ang II formation is different in the various vessels.

Angiotensin I↗

PubMed2000

Telerehabilitation at the University of Alberta.

We established a telerehabilitation system to link staff at the University of Alberta with clinicians and students located in Two Hills, a rural community approximately 180 km east of Edmonton. From February 1996 to March 1999, the faculty of Rehabilitation Medicine conducted a total of 254 telehealth sessions, most of which involved participants in the rehabilitation discipline. Of these connections, only 11 were unsuccessful owing to technical or telecommunication problems (i.e. 96% were successful). The average duration of a session was 1 h 15 min. There were benefits to the Faculty in the areas of clinical supervision of students, clinical consultation, undergraduate and graduate education as well as professional development. The future benefits of such an initiative will depend on how well we address challenges pertaining to training, human resource and infrastructure.

Alberta↗

PubMed2000

Creation and use of a composite polyurethane-expanded polytetrafluoroethylene graft for hemodialysis access.

The Thoratec (Vectra) polyurethane vascular access graft (TPVA) is among the most recent additions to the list of materials used to construct prosthetic grafts for vascular access during hemodialysis. We give the TPVA very high marks, and recognize the utility of such a graft for use in hemodialysis. However, the strong elasticity of this graft can lead to unexpected complications after suturing. We devised a new surgical method using a TPVA-ePTFE (expanded polytetrafluoroethylene) composite graft, substituting the anastomosis section of the TPVA with a portion of ePTFE graft material, and have been able to overcome most of the TPVA's potential problems. We herein describe the technique.

Aged↗

PubMed2000

Helicobacter pylori infection: relationship between seroprevalence and dietary preference in a rural area.

In order to evaluate the relationship between Helicobacter pylori (H. pylori) infection and dietary preference, a cross-sectional study was performed among 626 residents in a rural area of Japan. Seropositive rates were 88.7% in males and 71.4% in females, and these increased with age for both sexes [male P < 0.05 and female P < 0.01]. The relationship between H. pylori-seropositivities and salted-food intake, after adjustment for age, demonstrated a significant result in the "almost every day" group in males with an odds ratio (OR) of 8.39 and with 95% confidence intervals (CI) of 1.02-69.30. As regards an association between seropositivities of H. pylori and levels of serum pepsinogens for the screening of chronic atrophic gastritis (low pepsinogen values used were a pepsinogen I level below 70 ng/ml and a pepsinogen I/pepsinogen II ratio below 3.0), the ORs of H. pylori-seropositivities for low pepsinogen cases were 6.32 [95% CI: 1.42-28.03] in males and 12.72 [95% CI: 4.57-35.46] in females. With regard to the relationship between low pepsinogen cases and light-colored vegetables intake, a significant low OR for the low pepsinogen cases was obtained in the "almost every meal" group in females after adjustment for age and seropositivities of H. pylori with an OR of 0.37 and with 95% CI of 0.15-0.92.

Adult↗

PubMed2000

Prolonged swimming exercise training induce hypophosphatemic osteopenia in stroke-prone spontaneously hypertensive rats (SHRSP).

Stroke-prone spontaneously hypertensive rats (SHRSP) induce spontaneous osteoporosis. To elucidate the specific characteristics of bone metabolism, the SHRSP was compared with age matched Wistar-Kyoto (WKY) rats. We investigated the effects of prolonged swimming exercise training on bone mineral density (BMD) and metabolism in the SHRSP. Seven-week-old male SHRSP and WKY were divided into three groups; the sedentary control WKY group (n = 6, WKY), the sedentary control SHRSP group (n = 6, SP) and the swimming exercise training SHRSP group (n = 6, SWIM) (in pool with 60 min./day, 5 days/week for 12 weeks). The femoral BMD, bone mineral content (BMC), strength, Ca and P contents (%) of SHRSP were approximately 17, 27, 25, 20 and 9%, respectively, lower than that of WKY (p < 0.001). Serum alkaline phosphatase (AlP) had not changed between both of SP and WKY, but tartrate-resistant acid phosphatase (TrAcP) of SP approximately 3-fold higher than that of WKY (p < 0.05). Both serum calcium (Ca) and intact parathyroid hormone (i-PTH) were similar between SP and WKY. However, serum phosphate (P) of SP was approximately 18% lower than that of WKY (N.S.). These results suggested that SHRSP induces osteopenia by the bone turnover of the promoted osteoclast activity with disturbed phosphate homeostasis. On the other hand, the femoral BMD and strength were approximately 7% and 20%, respectively, decreased in the SWIM (p < 0.001), and femoral bone Ca and P contents (%) were also approximately 11% and 14%, respectively, lower than that of SP (p < 0.001). There were no significant difference between SWIM and SP on serum Ca, but serum P of SWIM was significantly lower than that of SP (p < 0.05). These results suggested that the prolonged swimming exercise training in the SHRSP induces more cruelly hypophosphatemia, and leading to osteopenia eventually. We conclude that SHRSP induces osteopenia with disturbance of phosphate homeostasis, and the prolonged swimming exercise in the SHRSP might deteriorate hypophosphatemia and osteopenia.

Animals↗

PubMed2000

Type II diabetes mellitus and primary Sjögren's syndrome complicated by pleural effusion.

A 73-year-old man was admitted to our hospital because of pleural effusion and nephrotic syndrome. Sjogren's syndrome (Sjs) was diagnosed based on a positive test for antibodies to Ro and La, and the result of labial salivary gland biopsy. The pleural effusion showed a high number of lymphocytes and high titers of antibodies to Ro and La. By immunohistochemistry, it was determined that infiltrating CD3+ cells predominated over infiltrating CD20+ cells in the pleura. Nephrotic syndrome was also present, which, as confirmed by renal biopsy was due to advanced diabetic nephropathy. Here, we report a case of Type II diabetes mellitus and primary Sjs complicated by pleural effusion, discuss the available treatment for pleural effusion.

Aged↗

PubMed2000

Comparison of mortality between respondents and non-respondents in a mail survey.

We conducted a population-based mail survey and prospectively compared mortality between respondents and non-respondents. Age-adjusted mortality rates for all causes were higher among non-respondents than among respondents in both sexes. Age-adjusted rate ratios were 1.50 for males and 1.33 for females. Non-respondents also had, in both sexes, higher mortality for three leading causes of death, namely, cancer, heart diseases and stroke than respondents. In particular, the difference between the two groups was much greater for cardiovascular disease than for cancer. Our results suggested that prospective studies using data from respondents to mail surveys in Japan would have underestimated the mortality for cardiovascular disease.

Adult↗

PubMed2000

Green tea consumption and chronic atrophic gastritis: a cross-sectional study in a green tea production village.

Chronic atrophic gastritis (CAG) is well known as a precancerous lesion of the stomach, and Helicobacter pylori (H. pylori) infection increases the risk of CAG. While recent studies have reported that green tea consumption decreases the risk of gastric cancer, there has been no study analyzing the relationship between green tea consumption and the both risks H. pylori infection and CAG. We conducted a cross-sectional study on 636 subjects living in a farming village in Japan to examine the relationship among green tea consumption, H. pylori infection, and CAG. Smoking, alcohol drinking, consumption of four beverages, including green tea, and of five foods were investigated as lifestyle factors that may affect H. pylori infection and CAG. The measurement of H. pylori-IgG antibodies was used to define H. pylori infection, and serum pepsinogens were used to define of CAG. The unconditional logistic regression model was used for analyzing each odds ratio (OR). H. pylori infection was positively associated with the risk of CAG (OR = 3.73; 95% confidence interval [CI], 2.59-5.36). High green tea consumption (more than 10 cups per day) was negatively associated with the risk of CAG, even after adjustment for H. pylori infection and lifestyle factors associated with green tea consumption (OR = 0.63; 95% CI, 0.43-0.93). These results support the hypothesis that high green tea consumption prevents CAG.

Adult↗

PubMed2000

Role of chymase on vascular proliferation.

In the normal state, vascular ACE regulates local angiotensin II formation and plays a crucial role in the regulation of blood pressure, whereas chymase is stored in secretory granules in mast cells and has no enzymatic effects such as angiotensin II-forming activity. Chymase has a maximal activity immediately upon release into the extracellular matrix in vascular tissues after mast cells have been activated by a strong stimulus such as experienced by catheter-injured and grafted vessels. Therefore, chymase plays an important role in forming local angiotensin II when vascular tissues are injured, and inhibition of chymase may be useful for preventing vascular proliferation in grafted vessels and after PTCA (Figure 6).

Angiotensin II↗