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Biomedical subjects

T Miyata

Publications and source records attributed to T Miyata.

At least 235 records · Page 13Linked to original sources
PubMed1998

Anastomotic aneurysms after surgical treatment of Takayasu's arteritis: a 40-year experience.

PURPOSE: To evaluate the clinical characteristics of anastomotic aneurysms that develop in surgically treated patients with Takayasu's arteritis. METHODS: Among 103 patients with Takayasu's arteritis treated surgically over 40 years, 91 patients with 259 anastomoses (allowing for exclusion of 12 operative deaths) participated in follow-up study from 1 month to 37.3 years with a mean value +/- SEM of 17.3 +/- 1.1 years with a follow-up completion rate of 93% at 30 years. The clinical characteristics of anastomotic aneurysms were clarified, and the influences of several factors (sites of anastomoses, occlusive or aneurysmal disease, suture material, preoperative systemic inflammation, and administration of corticosteroids) on formation of anastomotic aneurysms were analyzed by means of life-table method and Cox regression analysis. RESULTS: Twenty-two uninfected anastomotic aneurysms were found among 14 patients (22 of 259 anastomoses, 8.5%). The interval between the previous operation and diagnosis varied from 1.6 to 30 years with a mean value +/- SEM of 9.8 +/- 1.8 years. The cumulative incidence of anastomotic aneurysm at 20 years was 12.0%. Systemic inflammation or steroid administration had little influence on formation of anastomotic aneurysm. Instead, anastomotic aneurysm tended to occur after operations for aneurysmal lesions. CONCLUSIONS: Anastomotic aneurysm can occur anytime after operations for Takayasu's arteritis. The development of anastomotic aneurysm is not influenced by any factor specific to this disease except the presence of an aneurysmal lesion.

Adolescent↗
PubMed1998

Nondissection method for tibial bypass surgery using Esmarch's rubber bandage or an automatic sequential pneumatic tourniquet: long-term results.

It is suspected that operative injury to the native arteries during a vascular bypass procedure causes periarterial fibrosis contributing to late graft failure. A a nondissection method for tibial artery bypass has been developed using Esmarch's rubber bandage or an automatic sequential pneumatic tourniquet. This retrospective study examined patency and other late results in distal bypass operations using the nondissection method. Between June 1982 and July 1995, 78 tibial bypasses were performed using reversed autogenous saphenous vein grafts in 70 patients (57 men, 13 women; mean age 57.4 years). Graft patency was assessed angiographically. When a stenotic lesion was recognized, the graft was revised and considered an assisted primary patency. Primary patency rates at 1, 3, 5, and 10 years were 82.8%, 75.3%, 63.4% and 63.4%, respectively, by life-table analysis. Six grafts required revision for stenosis; one involved distal anastomotic stenosis. As a result, assisted primary patency rates resembled secondary patency rates of 87.7%, 84.3%, 80.3%, and 80.3% at the same respective intervals. In conclusion, the nondissection method improved long-term patency by preventing late distal anastomotic stenosis.

Arterial Occlusive Diseases↗
PubMed1998

Autoxidation products of both carbohydrates and lipids are increased in uremic plasma: is there oxidative stress in uremia?

BACKGROUND: Advanced glycation end products (AGEs), formed by non-enzymatic glycation and oxidation (glycoxidation) reactions, have been implicated in the pathogenesis of several diseases, including normoglycemic uremia. AGE research in uremia has focused on the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recent studies, however, have demonstrated that one AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fatty acids in vitro, raising the possibility that both carbohydrate and lipid autoxidation might be increased in uremia. METHODS: To address this hypothesis, we applied gas chromatography-mass spectrometry and high performance liquid chromatography to measure protein adducts formed in uremic plasma by reactions between carbonyl compounds and protein amino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and CML originating possibly from both sources. RESULTS: All three adducts were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with fructoselysine levels and were similar in diabetic and non-diabetic patients on hemodialysis, indicating that their increase was not driven by glucose. Pentosidine and MDA-lysine were also increased in plasma to the same extent in diabetic and non-diabetic hemodialysis patients. Statistical analysis indicated that plasma levels of CML correlated weakly (P < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine and MDA-lysine varied independently (P > 0.5). CONCLUSIONS: These data suggest that the increased levels of AGEs in blood, and probably in tissues, reported in uremia implicate a broad derangement in non-enzymatic biochemistry involving alterations in autoxidation of both carbohydrates and lipids.

Adult↗
PubMed1998

Functional quantitative analysis of the genome in cultured human mesangial cells. Technical note.

For normal physiological function, each cell tightly regulates gene expression in a specific fashion so that critical proteins are synthesized in a well-coordinated manner. Therefore, it is very important to uncover which genes are expressed in specific cells. Recent technological advances combined with rapid large-scale DNA sequencing and computerized data processing have allowed us to investigate the expression levels of a variety of transcripts in the mesangial cells, a target of injury in many forms of glomerulonephritis. Utilizing a large scale sequencing of a 3'-directed cDNA library, which allows us to avoid variable cloning efficiencies reflecting the size of cDNA, we investigated expression profiles of various molecules in cultured human mesangial cells. Among the 1,193 sequenced clones, 688 (57.7%) appeared more than once (redundant sequence group), representing 203 different species. Thirty-nine of these appeared more than three times. The most abundant mRNA was that of fibronectin, which consisted of 3.9% of the total mRNA population. Except for mitochondrial or ribosomal genes, calcyclin came next (2.5%), followed by two cytoskeletal genes, gamma-actin gene and calpactin 1 light chain gene, in addition to an amyloid precursor protein homolog (0.7%). In conclusion, we performed a molecular biological quantification of transcripts in mesangial cells. Fibronectin was the most abundantly expressed, followed by calcyclin, gamma-actin, calpactin 1 light chain, and an amyloid precursor protein homolog. We also discovered some candidate genes specific for human mesangial cells. The expression profile of the transcripts serves as an important tool in understanding the biological properties of mesangial cells.

Actins↗
PubMed1998

Renal catabolism of advanced glycation end products: the fate of pentosidine.

Advanced glycation end products (AGEs) generated through the Maillard reaction significantly alter protein characteristics. Their accumulation has been incriminated in tissue injury associated with aging, diabetes, and renal failure. However, little is known about their clearance from the body. The present study delineates the catabolic pathway of a well-defined AGE product, pentosidine. Synthesized pentosidine given intravenously in rats with normal renal function was rapidly eliminated from the circulation through glomerular filtration, but was undetectable in the urine by chemical analysis. Immunohistochemistry with anti-pentosidine antibody disclosed that pentosidine accumulated transiently in the proximal renal tubule one hour after its administration, but had disappeared from the kidney at 24 hours. After an intravenous load of radiolabeled pentosidine, radioactivity peaked in the kidney at one hour and subsequently decreased, whereas it rose progressively in the urine. Over 80% of the radioactivity was recovered in the 72-hour collected urine. However, only 20% of urine radioactivity was associated with intact pentosidine chemically or immunochemically. In gentamicin-treated rats with tubular dysfunction, up to 30% of the pentosidine load was recovered as intact pentosidine in the urine. The present study suggests that free pentosidine (and possibly other AGEs) is filtered by renal glomeruli, reabsorbed in the proximal tubule where it is degraded or modified, and eventually excreted in the urine. Kidney thus plays a key role in pentosidine disposal.

Animals↗
PubMed1998

Analysis of gene expression in homocysteine-injured vascular endothelial cells: demonstration of GRP78/BiP expression, cloning and characterization of a novel reducing agent-tunicamycin regulated gene.

An elevated plasma level of homocysteine is associated with arteriosclerosis and thrombosis. The mechanisms by which homocysteine may promote vascular diseases have not yet been elucidated. In the present study, we have applied a modified nonradioactive differential display analysis to evaluate changes in gene expression induced by homocysteine treatment of cultured human umbilical vein endothelial cells (HUVEC). We identified six upregulated and one downregulated gene. One upregulated gene was GRP78/BiP, a stress protein, suggesting that unfolded proteins would accumulate in the endoplasmic reticulum because of redox potential changes caused by homocysteine. Another upregulated gene encoded a bifunctional enzyme with activities of methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase, which is involved in a homocysteine metabolism. A third upregulated gene encoded activating transcription factor 4. The remaining four were uncharacterized genes. We isolated a full-length cDNA of one of the upregulated genes from a HUVEC library. It encoded a novel protein with 394 amino acids, which was termed reducing-agents and tunicamycin-responsive protein (RTP). Northern blot analysis revealed that RTP gene expression was induced in HUVEC after 4 h of incubation with homocysteine. RTP mRNA was also observed in unstimulated cells and induced by not only homocysteine but also 2-mercaptoethanol and tunicamycin. The mRNA was ubiquitously expressed in human tissues. These observations indicate that homocysteine can alter the expressivity of multiple genes, including a stress protein and several novel genes. These responses may contribute to atherogenesis.

Amino Acid Sequence↗
PubMed1998

Alterations of synovial tissue and their potential role in the deposition of beta2-microglobulin-associated amyloid.

BACKGROUND: Beta-2-microglobulin-associated amyloidosis (AB2M) is a frequent complication of long-term dialysis treatment. Uraemic retention of beta2-microglobulin (beta2M) apparently constitutes the basis for AB2M. However, it is unclear why clinical manifestations are largely confined to osteoarticular tissues. It has been speculated that synovial inflammatory changes, induced by uraemia and/or dialysis therapy could predispose this tissue to amyloid deposition. METHODS: We investigated which local synovial alterations preceded or paralleled amyloid deposition. Using immunohistology we evaluated synovial leukocyte infiltration (B and T lymphocytes, monocytes/macrophages), cell proliferation, fibroblast activation (de novo expression of alpha-smooth-muscle actin), the expression of extracellular matrix components (heparan sulphate proteoglycan, collagen types I, III, IV), and advanced glycation end-products (AGEs). RESULTS: Synovial AB2M was detected in 20 of 36 chronic peritoneal and haemodialysis patients and none of eight non-uraemic controls. Notably, non-AB2M synovial amyloid was present in six additional dialysis and three control patients. Cellular infiltration was largely restricted to patients with advanced AB2M deposits. The infiltrates consisted mainly of macrophages and progressed with increasing degrees of AB2M deposition. In advanced cases they exhibited characteristics of a foreign-body reaction. Other infiltrating leukocyte types, altered cell proliferation, or fibroblast activation were absent or uncommon in periarticular tissue of dialysis patients with and without AB2M. Neither dialysis treatment nor the presence of AB2M deposits appreciably altered the qualitative matrix composition in periarticular tissue. AGEs were present in AB2M deposits, the extracellular synovial matrix of dialysis patients (of both, patients with and without AB2M) and, to a lesser degree, in synovia of controls. CONCLUSIONS: These data suggest that, except for AGE formation, alterations of none of the parameters assessed, and in particular no inflammatory tissue alterations, precede periarticular AB2M. Rather synovial tissue, possibly modified by AGEs, seems to have an intrinsic propensity for amyloid deposition and inflammatory changes appear to only arise secondary to amyloid deposition.

Adult↗
PubMed1998

Changes of gene expression by lysophosphatidylcholine in vascular endothelial cells: 12 up-regulated distinct genes including 5 cell growth-related, 3 thrombosis-related, and 4 others.

Lysophosphatidylcholine (lysoPC), a component of oxidatively modified lipoproteins, is present in atherosclerotic lesions, and its proatherogenic properties have been demonstrated. To gain an insight into lysoPC-mediated endothelial gene expression, we applied nonradioactive differential display analysis of mRNA from lysoPC-treated and untreated human umbilical vein endothelial cells. We identified 12 up-regulated distinct genes including 5 cell growth-related genes (two phosphatases CL100 and B23/hVH-3, gravin, activating transcription factor-4, and heparin-binding epidermal growth factor-like growth factor), 3 thrombosis-related genes (plasminogen activator inhibitor-1, tissue plasminogen activator, and thrombomodulin), and 4 others (stanniocalcin, NAD-dependent methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase, BENE, and reducing agents and tunicamycin-responsive protein). We isolated a full-length cDNA of human gravin. The cDNA sequence of gravin was homologous with rat mitogenic regulatory gene or rat protein kinase C binding protein and substrate, suggesting that gravin would regulate cell growth. Thus, lysoPC apparently accelerates atherosclerosis by regulating the expression of a wide variety of genes. Our data suggest the involvement in atherogenesis of the genes hitherto regarded as atherosclerosis-unrelated.

A Kinase Anchor Proteins↗
PubMed1998

Localization of identified advanced glycation end-product structures, N epsilon(carboxymethyl)lysine and pentosidine, in age-related inclusions in human brains.

The recent identification of age-related accumulation of advanced glycation end-products (AGE) of the Maillard reaction in neurons and vessels of the human brain suggests the involvement of AGE in the aging process. A variety of inclusions such as lipofuscin granules, corpora amylacea, Hirano bodies, granulovacuolar degenerations and ubiquitin-positive granular structures are found in the aged human brain. These age-related inclusions contain insoluble and non-degradable proteins. Advanced glycation end-product-modified proteins are also known to be insoluble and protease resistant. The similarity between proteins in such inclusions and AGE-modified proteins suggests the presence of AGE in inclusions. To investigate this possibility, the presence of two known AGE structures, N epsilon(carboxymethyl)lysine (CML) and pentosidine, was examined in age-related inclusions. Immunohistochemical examination of the medial temporal area of brain tissues obtained at autopsy from seven non-demented elderly individuals demonstrated positive reactions in lipofuscin granules and corpora amylacea but not in other inclusions for anti-CML and anti-pentosidine antibodies. As CML and pentosidine are glycoxidation products among AGE, the results suggest that glycation and/or oxidation may be involved in the formation of lipofuscin granules and corpora amylacea.

Aged↗
PubMed1998

Current opinion of muco-active drug research: strategies and problems.

In general, mucoactive drugs are classified into several groups. However, since many drugs have overlapping effects, it is difficult to classify the drugs into groups based on their major actions. It has been reported that many mucoactive drugs have antioxidant effects. It is reasonable to suggest that an anti-inflammatory property is crucial to demonstrate effectiveness in a clinical context. From this point of view, we have evaluated several mucoactive drugs over two decades. Of these, we will consider the following drugs with anti-inflammatory properties: sodium aceneuramate; glucocorticoids; traditional Chinese medicines; and new cysteine derivatives. On the basis of these findings, we believe that the efforts to seek for compatible actions between glucocorticoids and oriental medicines may provide new opportunities for development of ideal mucoactive drugs with specified actions, i.e. suppression of gene expression.

Anti-Inflammatory Agents↗
PubMed1998

Effects of SS320A, a new cysteine derivative, on the change in the number of goblet cells induced by isoproterenol in rat tracheal epithelium.

We examined the effects of SS320A ((-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid), a new cysteine derivative, on the change in the number of goblet cells induced by isoproterenol in rat tracheal epithelium. Four types of goblet cells were characterized in tracheal epithelium according to their size and staining affinity with Alcian blue (AB) / periodic acid Schiff (PAS). When each rat was given a single daily injection of isoproterenol (0.05 mg/kg, i.p.) for 14 days, a significant increase was observed in AB/PAS-positive cells that were recognizable as goblet cells in tracheal epithelium. When SS320A (10-100 mg/kg, p.o.) or propranolol (1 mg/kg, s.c.) was administered before each injection of isoproterenol, the increase in the number of goblet cells induced by isoproterenol was significantly inhibited. There was no difference between male and female rats with regard to this inhibitory action. On the other hand, ambroxol, bromhexine, L-cysteine ethyl ester and S-carboxymethylcysteine (100 mg/kg, p.o., respectively), which are used as expectorants, had no inhibitory effects on the isoproterenol-induced change in the number of goblet cells. Four metabolites (M1-M4) of SS320A in rats also failed to inhibit the change induced by isoproterenol. These data suggest that SS320A itself may have a beneficial effect against mucus hypersecretion in chronic respiratory diseases.

Animals↗
PubMed1998

Local anti-inflammatory activity and systemic side effects of NM-135, a new prodrug glucocorticoid, in an experimental inflammatory rat model.

The local anti-inflammatory activity and systemic side effects of NM-135 (6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21[[2 ,3,4,6-tetrakis-O-(4-methylbenzoyl)-beta-D-glucopyranosyl]oxy]-pregna-1, 4-diene-3,20-dione) in croton oil-induced granuloma pouches and ear edema in rats were studied. The local anti-inflammatory activity of NM-135 was stronger than that of betamethasone 17-valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV) caused thymolysis at the doses required for the anti-inflammatory activity. In contrast, no clear systemic side effect was observed in rats administered NM-135 at the dose producing the anti-inflammatory activity. These results suggest that NM-135 is a drug exhibiting a high degree of dissociation between the local anti-inflammatory activity and systemic side effects.

Animals↗
PubMed1998

Inhibition of glycine-induced current by morphine in nucleus tractus solitarii neurones of guinea pigs.

We studied the effect of morphine on the current induced by glycine in acutely dissociated nucleus tractus solitarii (NTS) neurones of guinea pigs, by use of the whole-cell patch clamp technique. Morphine inhibited 30 microM glycine-induced current (Igly), without affecting the current caused by 30 microM GABA. The effect of morphine was concentration-dependent, with a maximal effect at 1 mM, and reversible. The half-maximum inhibitory concentration of morphine was 30 microM. The effect of morphine was not depressed by naloxone, an opioid antagonist. Furthermore, the effect was not substantially affected by methiothepin, a 5-HT1 antagonist, ketanserin, a 5-HT2 antagonist and MDL-72222, a 5-HT3 antagonist. Morphine at 30 microM shifted the concentration-response curve for Igly to the right without affecting the maximum value. The effect of morphine on Igly showed no use-dependence. The results indicate that morphine inhibits Igly in the NTS neurones, and further suggest that morphine at the concentration used may act on the glycine receptor-ionophore complex, but not on the Cl-channel of the complex.

Animals↗
PubMed1998

Bradykinin potentiates insulin-stimulated glucose uptake and enhances insulin signal through the bradykinin B2 receptor in dog skeletal muscle and rat L6 myoblasts.

Previously we demonstrated that bradykinin infusion could increase glucose uptake into dog peripheral tissues, and that bradykinin could potentiate insulin-induced glucose uptake through glucose transporter 4 (GLUT4) translocation in dog adipocytes. However, skeletal muscle is the predominant tissue for insulin-mediated glucose disposal. The aim of this study was to determine how bradykinin affected insulin-stimulated glucose uptake in dog skeletal muscle and myotubes transformed from rat L6 myoblasts. The bradykinin receptor binding studies revealed that dog skeletal muscle and rat L6 myoblasts possessed significant numbers of bradykinin receptors (Kd = 88 and 76 pmol/l, Bmax = 82.5 and 20 fmol/mg protein respectively). An RT-PCR (reverse transcriptase-polymerase chain reaction) amplification showed mRNA specific for bradykinin B2 receptor in both cells. Bradykinin significantly increased 2-deoxyglucose uptake in isolated muscle and L6 myoblasts in the presence of insulin (10(-7) mol/l) in a dose-dependent manner, but not in the absence of insulin. Bradykinin also enhanced insulin-stimulated GLUT4 translocation, and insulin-induced phosphorylation of insulin receptor beta subunit and insulin receptor substrate-1 (IRS-1) without affecting the binding affinities or numbers of cell surface insulin receptors in both cells. It is concluded that bradykinin could potentiate the insulin-induced glucose uptake through GLUT4 translocation in dog skeletal muscle and rat L6 myoblasts. This effect could be explained by the potency of bradykinin to upregulate the insulin receptor tyrosine kinase activity which stimulates phosphorylation of IRS-1, followed by an increase in GLUT4 translocation.

Animals↗
PubMed1998

Accumulation of carbonyls accelerates the formation of pentosidine, an advanced glycation end product: carbonyl stress in uremia.

Advanced glycation end product (AGE) formation is related to hyperglycemia in diabetes but not in uremia, because plasma AGE levels do not differ between diabetic and nondiabetic hemodialysis patients. The mechanism of this phenomenon remains elusive. Previously, it was suggested that elevation of AGE levels in uremia might result from the accumulation of unknown AGE precursors. The present study evaluates the in vitro generation of pentosidine, a well identified AGE structure. Plasma samples from healthy subjects and nondiabetic hemodialysis patients were incubated under air for several weeks. Pentosidine levels were determined at intervals by HPLC assay. Pentosidine rose to a much larger extent in uremic than in control plasma. Pentosidine yield, i.e., the change in pentosidine level between 0 and 4 wk divided by 28 d, averaged 0.172 nmol/ml per d in uremic versus 0.072 nmol/ml per d in control plasma (P < 0.01). The difference in pentosidine yield between uremic and control plasma was maintained in samples ultrafiltrated through a filter with a 5000-Da cutoff value and fortified with human serum albumin (0.099 versus 0.064 nmol/ml per d; P < 0.05). Pentosidine yield was higher in pre- than in postdialysis plasma samples (0.223 versus 0.153 nmol/ml per d; P < 0.05). These results suggest that a large fraction of the pentosidine precursors accumulated in uremic plasma have a lower than 5000 Da molecular weight. Addition of aminoguanidine and OPB-9195, which inhibit the Maillard reaction, lowered pentosidine yield in both uremic and control plasma. When ultrafiltrated plasma was exposed to 2,4-dinitrophenylhydrazine, the yield of hydrazones, formed by interaction with carbonyl groups, was markedly higher in uremic than in control plasma. These observations strongly suggest that the pentosidine precursors accumulated in uremic plasma are carbonyl compounds. These precursors are unrelated to glucose or ascorbic acid, whose concentration is either normal or lowered in uremic plasma. They are also unrelated to 3-deoxyglucosone, a glucose-derived dicarbonyl compound whose level is raised in uremic plasma: Its addition to normal plasma fails to increase pentosidine yield. This study reports an elevated level of reactive carbonyl compounds ("carbonyl stress") in uremic plasma. Most have a lower than 5000 Da molecular weight and are thus partly removed by hemodialysis. Their effect on pentosidine generation can be inhibited by aminoguanidine or OPB-9195. Carbonyl stress might contribute to AGE modification of proteins and thus to clinically relevant complications of uremia.

Aged↗
PubMed1998

Plasma levels of pentosidine in diabetic patients: an advanced glycation end product.

Nonenzymatic reactions between glucose and proteins yield advanced glycation end products (AGE) such as pentosidine. AGE accumulate in diabetic patients, alter the structure and function of tissue proteins, stimulate cellular response, and have thus been implicated in diabetic tissue damage. The present study was undertaken to assess the factors determining plasma total pentosidine level in diabetic patients and the possible relation between plasma pentosidine level and diabetic complications. In diabetic patients, including patients with renal failure, plasma pentosidine levels, assessed by HPLC assay, were correlated with serum creatinine (P < 0.0001). In patients with normal renal function, pentosidine levels were correlated with blood glucose control (hemoglobin Alc: P = 0.0028; fructoselysine: P = 0.0133), serum creatinine (P = 0.029), patient age (P = 0.0416), duration of diabetes (P = 0.0431), and total cholesterol (P = 0.0056) and LDL-cholesterol (P = 0.0208). Multiple regression analysis revealed an independent influence of hemoglobin Alc and serum creatinine on pentosidine levels (r2 = 0.216, P = 0.0026). Pentosidine levels were higher in patients with than in those without hypertension (P = 0.043) or ischemic heart diseases (P = 0.0061). No such differences were observed between patients with and without albuminuria or retinopathy. Multiple regression analysis revealed an independent influence of plasma pentosidine on the presence of hypertension (r2 = 0.129, P = 0.0382) and of plasma pentosidine and HDL-cholesterol on the presence of ischemic heart disease (r2 = 0.326, P = 0.0012). The present study demonstrated that plasma pentosidine level was significantly influenced by the quality of glycemic control and renal function. Pentosidine level was also correlated with hypertension and ischemic heart disease, and might be taken as a biomarker of diabetic cardiovascular risk.

Adult↗