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Biomedical subjects

T Miyata

Publications and source records attributed to T Miyata.

At least 289 records · Page 16Linked to original sources
PubMed1997

Implication of an increased oxidative stress in the formation of advanced glycation end products in patients with end-stage renal failure.

Recent studies have demonstrated a marked increase in the level of advanced glycation end products (AGEs) in the plasma, skin and amyloid fibrils of hemodialysis (HD) patients. The presence of AGEs in (beta2m) forming amyloid fibrils has been established in a previous immunochemical study relying on a monoclonal anti-AGE antibody. In the present study, Western blot analysis and immunohistochemistry reveal that the epitope recognized by this antibody is N epsilon-(carboxymethyl)lysine (CML) and that CML is one of the AGE structures present in amyloid fibrils. Thus, two AGE structures, CML and pentosidine, are now recognized in dialysis-related amyloidosis. AGE accumulation in uremia is not accounted for by elevated glucose levels. Since CML and pentosidine formation are closely linked to oxidative processes, we tested the hypothesis that a high oxidative stress enhanced AGE formation in HD patients. We focused on ascorbic acid (AA) because AA is easily oxidized under oxidative stress and its oxidized form (oxiAA) is a source of CML and pentosidine. In vitro incubation of beta2m with AA under atmospheric oxygen resulted in: (1) the rapid appearance of characteristic physicochemical properties of AGEs (brown color, fluorescence, polymerization tendency); (2) the transformation of beta2m into AGE-modified beta2m recognized by a specific monoclonal antibody; and (3) the accelerated formation of CML in beta2m and beta2m-peptide, recognized by mass spectrometry. A similar in vitro incubation of human serum albumin disclosed a parallel production of pentosidine measured by high-performance liquid chromatographic assay. In HD patients, the degree of AA oxidation, assessed as the ratio of oxiAA to total ascorbate, was more than twice as high as that of normal subjects (0.87 +/- 0.16 vs. 0.35 +/- 0.11, P < 0.0001), suggesting the presence of an increased oxidative stress. Interestingly, plasma level of oxiAA was correlated with the plasma levels of protein linked (P < 0.01, r2 = 0.25) and free (P < 0.05, r2 = 0.22) pentosidine. Altogether these results demonstrate that AGE, that is, CML and pentosidine, production is accelerated under oxidative stress, even in the absence of glucose. They suggest that, in uremia, CML and pentosidine production is determined both by an increased oxidative stress and the availability of precursors such as oxiAA. Finally, both CML and pentosidine contribute to the AGEs present in dialysis-related amyloid fibrils.

Amino Acid Sequence↗
PubMed1997

Inhibition of glycine currents by dextromethorphan in neurones dissociated from the guinea-pig nucleus tractus solitarii.

1. The effect of dextromethorphan (DM) on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea-pigs was studied by use of the whole-cell patch clamp technique. The effect of DM on gamma-aminobutyric acid (GABA)-induced currents (IGABA) was also examined. 2. DM inhibited 30 microM glycine-induced current (IGly), without affecting the current caused by 30 microM GABA. The action of DM was concentration-dependent, with a maximum effect at 100 microM, and reversible. The half-maximum inhibitory concentration (IC50) of DM was 3.3 microM, about 85 times higher than that of strychnine. 3. DM 3 microM shifted the concentration-response curve for glycine to the right without affecting the maximum value. DM 10 microM shifted the curve even more to the right, although it was not a parallel shift. Strychnine at a concentration of 0.1 microM shifted the curve for glycine in a nearly parallel fashion. 4. The effect of 10 microM DM was slightly weak voltage-dependency, but the lower concentration of DM, 3 microM, inhibited IGly equally at -50 mV and +50 mV. The effect of 3 microM DM on IGly showed no use-dependence. Blockade by strychnine 0.1 microM showed no voltage- or use-dependence. 5. The results indicate that DM inhibits IGly in single neurones of NTS, and further suggest that DM at a low concentration may act on the glycine receptor-ionophore complex, but not on the Cl channel of the complex. However, a relatively high concentration of DM may at least partly affect the Cl- channel of the complex.

Animals↗
PubMed1997

Oxidation conspires with glycation to generate noxious advanced glycation end products in renal failure.

The causes of long-term complications of uraemia are yet to be fully elucidated. It has recently been demonstrated that renal failure is associated with a dramatic elevation of advanced glycation end products (AGEs). These products are the result of the non-enzymatic Maillard reaction linking a protein amino group with a glucose-derived aldehyde group. A mild rise of AGEs is associated with normal ageing. Proteins with a slow turnover such as matrix proteins are thus modified and removed by an AGE-specific receptor-mediated process thought to be a part of normal tissue remodelling. A more striking rise of AGEs is observed in diabetic patients as a result of sustained hyperglycaemia. A greater variety of proteins is thus modified leading to tissue damage through alteration of tissue protein structure and function, stimulation of several cellular responses, or generation of reactive oxygen species. In uraemia, the rise of AGEs is even more marked than in diabetics and is associated with a variety of tissue disorders including vascular damage, dyslipidaemia, and beta 2-microglobulin amyloidosis. AGE accumulation in uraemia does not result from hyperglycaemia. Identification of its cause as well as of the involved precursors should contribute to the understanding of uraemic toxicity and open new therapeutic approaches. In this presentation, we propose the hypothesis that AGE generation is enhanced by an increased oxidative stress associated with uraemia. Under these conditions, a variety of compounds, both related and unrelated to glucose, may contribute to the advanced glycoxidation of proteins. In uraemia, AGEs could be taken as a marker of oxidative stress damage to proteins.

Glycation End Products, Advanced↗
PubMed1997

Evaluation of collagen gel and hyaluronic acid as vitreous substitutes.

We evaluated alkaline-solubilized collagen, hyaluronic acid (HA), and a substance formed from mixing both materials as vitreous substitutes in the rabbit. Fluorescein isothiocyanate (FITC)-labeled collagen (2%), fluorescein-labeled HA (FLHA, 1%), or the mixture was injected into the rabbit vitreous after vitrectomy. After 3 months, histologic study revealed that the substitutes caused no adverse effects on the ocular tissue. Kinetic studies showed that the half-lives of FITC-collagen, FL-HA, and the mixed substance were 5.70, 2.09, and 8.41 days, respectively. The results indicated that HA enhances the collagen half-life. The concomitant of collagen and HA is safe and effective for 3 months in rabbit's eye as a vitreous substitute, and the mixture is capable of tamponade.

Animals↗
PubMed1997

Lysozyme loading and release from hydrogels carrying pendant phosphate groups.

To develop a polymeric matrix for efficiently loading cationic biomolecules, polyelectrolyte hydrogels carrying pendant phosphate groups were synthesized by copolymerizing 2-methacryloyloxyethyl dihydrogen phosphate with N-isopropylacrylamide and N, N1-methylene-bis-acrylamide. The phosphate-carrying monomer yielded anionic hydrogels, which formed ionic complexes with the cationic protein, lysozyme. It was shown that the amount of complexed lysozyme reached 2.1 g g-1 dry gel, corresponding to 1.3 x 10(-3) mol phosphate group per gram lysozyme, when 40 mol% of phosphate-carrying monomer was incorporated in a hydrogel. When the hydrogel complexed with lysozyme was placed in deionized water and various KCl solutions, of varying concentrations of up to 0.5 M KCl, no lysozyme was released in deionized water, while increasing amounts of lysozyme were released as the KCl concentration increased. This confirmed that lysozyme was loaded in the hydrogel through electrostatic interactions. It was further found that the complexed lysozyme retained its enzymatic activity after being released from the hydrogel. These results suggest the use of this system for the controlled release of cationic protein drugs.

Biocompatible Materials↗
PubMed1997

Clinical analysis of abdominal aortic aneurysms associated with iliofemoral occlusive disease.

Patients with abdominal aortic aneurysm (AAA) associated with iliofemoral occlusive disease due to arteriosclerosis obliterans (ASO) are often encountered clinically, but their clinical characteristics remain poorly defined. We divided 275 patients undergoing aneurysmectomy into 2 groups: 58 patients with both AAA and ASO (Group A) and 217 patients with AAA only (Group B). General characteristics, morphological features of the aneurysms, surgical procedures and operative results were then compared between the groups. In Group A, ruptured aneurysms were significantly less common (p = 0.005) and the aneurysms were smaller (p = 0.0009). The most common cause of death in Group A was acute myocardial infarction (3/7), in contrast to aneurysmal rupture of another arterial segment and malignancy (6/27, each) in Group B. These findings indicate that patients with AAA and ASO represent a subgroup of patients with particular clinical features.

Aged↗
PubMed1997

Surgical results of abdominal aortic aneurysm repair in patients with chronic renal dysfunction.

The purpose of this study was to determine the influence of preoperative renal dysfunction on the outcome of patients undergoing elective, infrarenal abdominal aortic aneurysm (AAA) repair. Patients undergoing AAA repair from 1984 to 1996 (n = 250) were divided into 2 groups, according to their preoperative serum creatinine levels: > or = 1.5 mg/dl (group A, n = 33) and < 1.5 mg/dl (group B, n = 217). There was no apparent difference in the incidences of preoperative risk factors, excluding ischemic heart disease, between the groups. The mortality rates of the 2 groups did not differ (9.9% vs 3.2% in groups A and B, respectively, p = 0.13), but the morbidity rate of group A (30.3%) was significantly higher than that of group B (12.9%, p = 0.0095). The 5-year cumulative survival rate of group A patients was 60%, which was significantly lower (p < 0.0001) than that of group B patients (84%). Five group A patients underwent simultaneous renal artery reconstruction, which relieved postoperative renal deterioration in 4, although 2 of them developed chronic renal failure requiring hemodialysis over 5 years after the operation. These findings suggest that morbidity and long-term survival in patients with renal dysfunction can be severe after AAA repair and that simultaneous renal artery reconstruction may delay renal function decline.

Aged↗
PubMed1997

[Bakumondo-to, a traditional herbal medicine, stimulates phosphatidylcholine secretion, through the synergistic cross-talk between different signal transduction systems in alveolar type II cells].

Traditional herbal medicines, Kampo medicines in Japan, are composed of various herbs with ubiquitous pharmacological activities. We previously found that Bakumondo-to stimulates phosphatidylcholine (PC) secretion from alveolar type II cells. To define the regulatory mechanisms involving in the Bakumondo-to-induced PC secretion, we investigated the effect of Bakumondo-to on signal transduction systems in alveolar type II cells, Bakumondo-to-induced PC secretion was completely inhibited by each of H-89, H-7 or BAPTA-AM, protein kinase A (PKA), protein kinase C (PKC) or intracellular Ca2+ inhibitor. In addition, Bakumondo-to increased cellular cyclic AMP content and Ca2+ content, too. These results suggested that the secretagogue effect of Bakumondo-to may be coupled to the synergistic cross-talk between cyclic AMP- and Ca(2+)-dependent system. To investigate if there is cross-talk between different signaling systems in type II cells, we examined the combined effects of various secretagogues on PC secretion. The combination of terbutaline and PMA potentiated stimulation of secretion, although the effects of terbutaline with A23187, or PMA with A23187 were additive. This synergism seemed to be mediated by Ca2+ influx, because this combination significantly increased cellular Ca2+ content. These findings suggested that there is synergistic cross-talk between PKA- and PKC dependent signaling system in alveolar type II cells, and that Bakumondo-to may stimulate PC secretion through this cross-talk.

Animals↗
PubMed1997

Dexamethasone increases beta 2-adrenoceptor-regulated phosphatidylcholine secretion in rat alveolar type II cells.

Insufficient production of pulmonary surfactant in alveolar type II cells is relevant to many lung diseases. To cure its deficiency, glucocorticoid is commonly used in clinical areas. In the present study, we investigated the effect of dexamethasone on the secretion of phosphatidylcholine, a major phospholipid of pulmonary surfactant, in a primary culture of rat alveolar type II cells. Dexamethasone had no effect on the basal secretion rate of phosphatidylcholine. Dexamethasone augmented both the phosphatidylcholine secretion and the cyclic AMP formation increased by terbutaline. Furthermore, dexamethasone increased the number of beta-adrenoceptors and mRNA expression of beta 2-adrenoceptors in type II cells. These findings indicate that dexamethasone increases pulmonary surfactant secretion through an enhancement of beta 2-adrenoceptor gene expression.

Adrenergic beta-Agonists↗
PubMed1997

Effects of xanthine derivatives on phosphatidylcholine secretion in rat type II pneumocytes in the presence of activated eosinophils.

We have previously reported that activated eosinophils enhanced the phosphatidylcholine (PC) secretion in type II pneumocytes. In this study, we have determined whether xanthine derivatives affect the PC secretion increased by activated eosinophils. Theophylline enhanced the increased PC secretion at 10(-5) M. 8-Phenyltheophylline dose-dependently enhanced the PC secretion. The enhanced secretion by either theophylline at 10(-5) M or 8-phenyltheophylline was suppressed by superoxide dismutase in combination with catalase. Pentoxifylline did not enhance the PC secretion increased by activated eosinophils, although it increased the PC secretion by itself. The PC secretion increased by theophylline at 10(-3) M or pentoxifylline was not suppressed by superoxide dismutase in combination with catalase. The present results suggest that xanthine derivatives increased the PC secretion in the co-culture of type II pneumocytes and activated eosinophils possibly through the inhibition of phosphodiesterases or the antagonism of adenosine receptors of the eosinophils.

Animals↗
PubMed1997

Effect of human neutrophil elastase on tracheal mucociliary transport in anesthetized quails.

We investigated the effect of human neutrophil elastase (HNE) on tracheal mucociliary transport in anesthetized quails. Topical application of HNE (30-300 microg/kg) to tracheal mucosa dose-dependently decreased mucociliary transport velocity (MCTV). The HNE (300 microg/kg)-induced decrease in MCTV was blocked by ONO-5046 x Na (sodium N-[2-[4-(2,2-dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetate tetrahydrate) (3-30 mg/kg, i.m.), a specific neutrophil elastase inhibitor. Furthermore, we found that HNE increased DNA, fucose and protein contents of tracheal lavages, and the increases were also reverted by ONO-5046 Na. These results indicated that HNE decreased tracheal mucociliary transport, and the decrease may be, at least in part, ascribed to the deterioration of tracheal secretions.

Animals↗
PubMed1997

Assessment of the accuracy of indirect blood pressure measurements.

This study assessed the accuracy of indirect blood pressure (BP) measurements by simultaneously performing three kinds of indirect BP measurement on the left arm (auscultatory, microphone and oscillometric methods) and a direct BP measurement on the left arm. The subjects were 34 hospitalized patients, ranging in age from 18 to 73 years (average 47.5 years). Highly significant correlations in systolic or diastolic BP between a given pair of the three indirect methods. The indirect methods underestimated systolic BP and overestimated diastolic BP compared with the direct method, with differences of -12.2 +/- 10.5/+4.6 +/- 7.6 (systolic/diastolic BP) with the oscillometric method, -8.1 +/- 9.7/+1.2 +/- 8.9 with the microphone method and -10.6 +/- 8.1/+3.7 +/- 6.5 mmHg with the auscultatory method. The difference in systolic BP between the auscultatory and direct methods was greater and the difference in diastolic BP was smaller in subjects older than 50 years than in those aged 50 years or less (p < 0.001 for systolic BP, p < 0.05 for diastolic BP). The auscultatory method revealed greater systolic BP in subjects with increased carotid arterial wall stiffness assessed by echoarteriography. Thus, it is concluded that there are inherent differences in BP between the indirect and direct methods which can be attributed to the changes in arterial wall physical properties partly due to aging.

Adolescent↗
PubMed1997

Advanced glycation end products enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted subcutaneously with devitalized bone particles.

Advanced glycation end products (AGE) are formed in long-lived matrix proteins by a nonenzymatic reaction with sugar. The presence of AGE in beta 2-microglobulin-amyloid fibrils of dialysis-related amyloidosis, one of the characteristic features of which is an accelerated bone resorption around amyloid deposits, was recently demonstrated. This suggested a potential link of AGE in bone resorption and initiated this investigation of whether AGE enhance bone resorption. When mouse unfractionated bone cells containing osteoclasts were cultured on dentin slices, both AGE-modified beta 2-microglobulin and BSA increased the number of resorption pits formed by osteoclasts, whereas their normal counterparts of those modified with the early glycation products did not. AGE proteins, however, did not increase the number of newly formed osteoclasts, even in the coculture of mouse bone marrow cells with osteoblastic cells isolated from mouse calvaria. Enhanced bone resorption was also observed when unfractionated bone cells were cultured on AGE-modified dentin slices. AGE-enhanced bone resorption was effectively inhibited by calcitonin and ipriflavone, both of which are inhibitors of bone resorption. AGE-enhanced bone resorption was further supported by in vivo evidence that rat bone particles-upon incubation with glucose for 60 days (AGE-bone particles)-when implanted subcutaneously in rats, were resorbed to a much greater extent than control bone particles upon parallel incubation without glucose. These findings suggest that AGE enhance osteoclast-induced bone resorption. Although the mechanism remains unknown, AGE are unlikely to promote differentiation of osteoclast progenitors into osteoclasts, suggesting that AGE activate osteoclasts or alter microenvironments favorable for bone resorption by osteoclasts. The modification of bone matrices with AGE might play a role in the remodeling of senescent bone matrix tissues, further implicating a pathological significance of AGE in dialysis-related amyloidosis or osteoporosis associated with diabetes and aging.

Amyloidosis↗
PubMed1997

Color Doppler ultrasonography in the diagnosis of portal vein invasion in patients with pancreatic cancer.

We retrospectively evaluated the diagnostic usefulness of color Doppler ultrasonography for detecting portal vein invasion in 21 patients with pancreatic cancer who underwent surgical exploration (14 resection, seven inspection). Real-time gray scale ultrasonography, color Doppler ultrasonography, computed tomography, and angiography were performed in all patients to evaluate portal vein invasion, and the images were compared with the histopathologic or surgical inspection findings. On comparison between gray scale ultrasonographic and color Doppler ultrasonographic images, the tumor-vessel relations were visualized more clearly on color Doppler ultrasonography than on gray scale ultrasonography in 14 (22.2%) of 63 vessels. The sensitivity of color Doppler ultrasonography, computed tomography, and angiography for diagnosing portal invasion was 73.7%, 73.7%, and 73.6%, and the specificity was 95.1%, 95.5%, and 90.9%, respectively; the overall accuracy was 84.1%, 88.9% and 85.7%, respectively. A mosaic signal pattern was observed in 12 vessels and showed an accuracy of 86.4% for diagnosing portal vein invasion. In conclusion, compared with gray scale ultrasonography, color Doppler ultrasonography provided improved images of the tumor and portal vein. Furthermore, the accuracy of color Doppler evaluation of portal vein invasion appears to be equal to that of computed tomography and angiography. Therefore, color Doppler ultrasonography may play an important role as an initial examination for evaluating portal vein invasion.

Adult↗