Search PubMed⌕ Search

Biomedical subjects

T Miyata

Publications and source records attributed to T Miyata.

At least 253 records · Page 14Linked to original sources
PubMed1998

Implication of the glycoxidation and lipoxidation reactions in the pathogenesis of dialysis-related amyloidosis (Review).

Dialysis-related amyloidosis is recognized as a serious bone and joint complication in long-term dialysis patients. Beta2-microglobulin has been demonstrated to be a major constituent of the amyloid fibrils. However, the molecular pathogenesis of this disorder remains unknown. Recent biochemical and immunohistological studies have identified a new modification of beta2-microglobulin in the amyloid fibrils, i.e., the advanced glycation end products (AGEs). AGEs are formed by non-enzymatic glycative and oxidative (glycoxidation) reactions. The levels of AGEs, such as pentosidine and carboxymethyllysine (CML), are elevated in both the plasma proteins and skin collagen of non-diabetic dialysis patients several times more than in normal subjects. The AGE accumulation in uremia cannot be attributed to hyperglycemia, nor simply to their decreased renal clearance. Recently, gathered evidence has suggested that, in uremia, an increase in carbonyl compounds, derived from both carbohydrates and lipids, modifies proteins, leading to the augmentation of the production of not only AGEs, but also the advanced lipoxidation end products (ALEs). Uremia might thus be a state of carbonyl overload with potentially damaging proteins ('carbonyl stress'). Immunohistochemical studies, with antibodies specific to AGEs and ALEs, identified carbonyl stress in long-lived beta2-microglobulin amyloid deposits. Furthermore, proteins modified by carbonyl stress exhibit a variety of biological activities towards several types of cells, which might partially account for dialysis arthropathies.

Amyloid↗
PubMed1998

Lysophosphatidylcholine decreases the synthesis of tissue factor pathway inhibitor in human umbilical vein endothelial cells.

Thrombotic complications are frequently associated with atherosclerosis. Lysophosphatidylcholine (LPC), a component accumulated in oxidatively modified LDL (ox-LDL), is known to play a crucial role in the initiation and progression of atherosclerotic vascular lesions. Since a vascular anticoagulant, tissue factor pathway inhibitor (TFPI), has the function of regulating the initial reaction of tissue factor (TF)-induced coagulation, we investigated the effect of LPC on TFPI synthesis in cultured human umbilical vein endothelial cells (HUVEC). The treatment of HUVEC with LPC for 24 h decreased TFPI antigen levels in both the culture medium and the cell lysate in a dose-dependent manner. Northern blot analysis revealed that LPC caused a time-dependent decrease in the TFPI mRNA levels. The levels of TFPI antigen and mRNA were decreased to 72% and 38%, respectively, by the incubation with 50 microM LPC for 24 h. The down-regulation by LPC of TFPI mRNA expression was not observed in the presence of cycloheximide, suggesting that protein synthesis was involved in the suppression of TFPI mRNA expression. The TFPI mRNA levels in actinomycin D-treated cells were relatively stable, indicating that the down-regulation of TFPI mRNA by LPC would be partly explained by the enhanced mRNA destabilization. In contrast to the significant down-regulatory effects of LPC on TFPI expression, LPC did not induce TF mRNA expression in HUVEC. These results indicate that LPC accumulated in the atherosclerotic vascular wall would suppress endothelial TFPI synthesis, reducing the antithrombotic property of endothelial cells.

Cells, Cultured↗
PubMed1998

Factor X Nagoya 1 and Nagoya 2: a CRM- factor X deficiency and a dysfunctional CRM+ factor X deficiency characterized by substitution of Arg306 by Cys and of Gly366 by Ser, respectively.

We have identified, in two unrelated patients, factor X deficiency that we have designated factor X Nagoya 1 and Nagoya 2, respectively. The proband with factor X Nagoya 1 showed factor X activity level of 3% and factor X antigen level < 10% of the normal control value. All the exons and intron/exon junctions of the factor X gene were studied using a strategy combining polymerase chain reaction (PCR) amplification and nonradioactive single-strand conformational polymorphism (SSCP) analysis. Exon 8 containing DNA fragment of the proband with factor X Nagoya 1 showed aberrant migration on SSCP analysis. All exon-containing DNA fragments amplified by PCR were sequenced, and we identified a C-to-T substitution in exon 8 in the human factor X gene of the proband, which results in the replacement of Arg306 by Cys. This genetic defect has been transmitted from her father, and her sister also carried the same mutation; both showed almost half the normal levels of both factor X activity and antigen. The coordinates of human factor Xa indicated that Arg306 in the catalytic domain is positioned at the beginning of the alpha-helix near the second EFG-like domain. The substitution for Arg of Cys has been supposed to cause the destruction of local alpha-helix formation, possibly leading to the secretion problem. The proband with dysfunctional factor X Nagoya 2 was characterized by factor X activity level of 34% with normal factor X antigen level of 80%. We identified one substitution of G for A in exon 8 in the human factor X gene of the proband, which results in the replacement of Gly366 by Ser. As the Gly366 is positioned at the primary substrate binding pocket. the replacement of Gly with Ser would cause a defect of substrate binding, leading to the loss of enzymatic activity.

Adult↗
PubMed1998

Tibioperoneal bypass for popliteal arterial occlusion.

OBJECTIVE: To clarify the clinical features of chronic arterial occlusive disease in which the main lesion occurs in the popliteal artery (OPA). EXPERIMENTAL DESIGN: This was a retrospective study with a follow-up of 1 to 163 months. SETTING: A department of surgery in a university hospital. PATIENTS: Fifty-six patient who underwent tibioperoneal bypasses: 31 patients with OPA, and 25 with an extensive occlusive lesion from the femoral to popliteal artery (OFPA). INTERVENTION: All bypasses were performed using reversed saphenous veins under tourniquet ischemia. MEASUREMENTS: The background of the patients and the surgical results, including long-term patency and postoperative arteriographic findings. RESULTS: Buerger's disease occurred most commonly in the OPA group (49%) and arteriosclerosis obliterans occurred most commonly in the OFPA group (64%). The 3-year primary and secondary cumulative patency rates of the grafts for OPA were 72% and 85% respectively, and were comparable with those of OFPA. Arteriographic analyses carried out in the follow-up period revealed no occlusive progression in the inflow artery. CONCLUSIONS: Popliteal-distal bypass is a reliable procedure in selected patients with OPA.

Adult↗
PubMed1998

Continuous hemodiafiltration during aortic arch aneurysm repair in chronic renal failure patient.

We report the successful repair of a distal aortic arch aneurysm in a patient with chronic renal failure following aneurysmectomy for a ruptured abdominal aorta. Perioperative use (during and up to 47 hrs after the operation) of continuous hemodiafiltration was useful for controlling fluid balance and uremia without any complicating hemodynamic instability. However, this should be restricted to the first two or three days after the operation, since it poses risk of significant thrombocytopenia.

Aortic Aneurysm, Thoracic↗
PubMed1998

[Differential diagnosis of pancreatic tumor by contrast enhanced color Doppler ultrasonography].

For evaluating abdominal hemodynamic changes and diagnosing mass lesion, recently color Doppler ultrasonography (CDUS) have been applied. However, there are limitations in visualizing Doppler signals in small vessels with low flow velocity. To overcome these shortcomings, several contrast agents that facilitate evaluation of abdominal hemodynamics have been developed. We underwent Contrast enhanced color Doppler ultrasonography (CECD) with a galactose-based contrast agent in three patients with pancreatic tumor. In the patient with tumor forming pancreatitis, only CECD visualized the color signal in and around the tumor. In the patient with duct cell cancer, CDUS and CECD visualized only the color signal of the splenic artery penetrating the tumor, whereas in the patient with islet cell tumor, CECD visualized numerous color signals in the tumor. CECD appears to be useful in diagnosing pancreatic tumor.

Adult↗
PubMed1998

Effect of antibiotics on rat leukocyte function.

Many antibiotics are used to treat infection in clinical practice. Actions of these drugs involve specific immune enhancement and improved overall phagocytic and bactericidal capacities of polymorphonuclear leukocytes and macrophages at the site of infection. In this study, we examined the effects of antibiotics on chemotaxis and phagocytosis by reacting macrophages with 7 different antibiotics, specifically ampicillin (ABPC), cephalexin (CEX), cefotiam (CTM), amikacin (AMK), clindamycin (CLDM), tetracycline (TC) and bleomycin (BLM). At 1 microgram/ml, there were significant differences in chemotaxis between control and experimental groups treated with agents other than ABPC and CEX (CLDM: p < 0.05, AMK: p < 0.01, CTM, TC and BLM: p < 0.001). At 10 micrograms/ml, there were significant differences in chemotaxis between the control group and all treated groups (ABPC and CLDM: p < 0.01, CEX, CTM, AMK, TC and BLM: p < 0.001). At 100 micrograms/ml, all antibiotics significantly inhibited chemotaxis (p < 0.001). Phagocytosis was evaluated by determining both the ratio and index of phagocytosis. There was a significant difference in the phagocytosis ratio between the control group and the group treated with 10 micrograms/ml of BLM (p < 0.001). At 100 micrograms/ml, all agents but ABPC significantly reduced phagocytosis in a dose-dependent manner. Agents other than ABPC similarly reduced the phagocytosis index. Significant differences were noted between the control group and groups treated with BLM or AMK (BLM: 10 micrograms/ml: p < 0.01, 100 micrograms/ml: p < 0.001, AMK: 100 micrograms/ml: p < 0.01).

Amikacin↗
PubMed1997

Molecular evolution of amphioxus fructose-1,6-bisphosphate aldolase.

The cDNA for amphioxus fructose-1,6-bisphosphate (FBP)-aldolase was isolated and its nucleotide sequence was determined. In the cDNA, there existed a probable open reading frame comprising 1080 bp; hence, 359 amino acid residues were deduced. The amino acid sequence indicates the deletion of 4 residues from N-terminus, in comparison with the sequence of FBP-aldolase isozymes from other sources. There was only one FBP-aldolase gene, and one enzyme species corresponding, in the amphioxus; this is the first report of the existence of a single FBP-aldolase species in animals. Enzymatic studies of both native and the recombinant FBP-aldolase suggest that the amphioxus enzyme belongs to an ancestral class I type which is not discovered among vertebrate aldolase isozymes.

Amino Acid Sequence↗
PubMed1997

Immunohistochemical colocalization of glycoxidation products and lipid peroxidation products in diabetic renal glomerular lesions. Implication for glycoxidative stress in the pathogenesis of diabetic nephropathy.

Advanced glycation end products (AGEs) include a variety of protein adducts whose accumulation alters the structure and function of tissue proteins and stimulates cellular responses. They have been implicated in tissue damage associated with diabetic complications. To assess the possible link between AGE accumulation and the development of diabetic nephropathy (DN), we have examined the immunohistochemical localization of various AGE structures postulated to date, i.e., pentosidine, Nepsilon-(carboxymethyl)lysine (CML), and pyrraline, in diabetic and control kidneys. CML and pentosidine accumulate in the expanded mesangial matrix and thickened glomerular capillary walls of early DN and in nodular lesions and arterial walls of advanced DN, but were absent in control kidneys. By contrast, pyrraline was not found within diabetic glomeruli but was detected in the interstitial connective tissue of both normal and diabetic kidneys. Although the distribution of pyrraline was topographically identical to type III collagen, distribution of pentosidine and CML was not specific for collagen type, suggesting that difference in matrix protein composition per se could not explain heterogeneous AGE localization. Since oxidation is linked closely to the formation of pentosidine and CML, we also immunostained malondialdehyde (MDA), a lipid peroxidation product whose formation is accelerated by oxidative stress, assuming that local oxidative stress may serve as a mechanism of pentosidine and CML accumulation. Consistent with our assumption, diabetic nodular lesions were stained positive for MDA. These findings show that AGE localization in DN varies according to AGE structure, and suggest that the colocalization of markers of glycoxidation (pentosidine and CML) with a marker of lipid peroxidation reflects a local oxidative stress in association with the pathogenesis of diabetic glomerular lesions. Thus, glycoxidation markers may serve as useful biomarkers of oxidative damage in DN.

Adolescent↗
PubMed1997

A truncated Reelin protein is produced but not secreted in the 'Orleans' reeler mutation (Reln[rl-Orl]).

Reelin is the protein defective in reeler mutant mice [I. Bar, C. Lambert de Rouvroit, I. Royaux, D.B. Krizman, C. Dernoncourt, D. Ruelle, M.C. Beckers, A.M. Goffinet, A YAC contig containing the reeler locus with preliminary characterization of candidate gene fragments, Genomics 26 (1995) 543-549; G. D'Arcangelo, G.G. Miao, S.C. Chen, H.D. Soares, J.I. Morgan, T. Curran, A protein related to extracellular matrix proteins deleted in the mouse mutant reeler, Nature 374 (1995) 719-723; S. Hirotsune, T. Takahara, N. Sasaki, K. Hirose, A. Yoshiki, T. Ohashi, M. Kusakabe, Y. Murakami, M. Muramatsu, S. Watanabe, K. Nakao, M. Katsuki, Y. Hayashizaki, The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons, Nature Genet. 10 (1995) 77-83]. In the Orleans allele of reeler (symbol: Reln[rl-Orl]), a 220 nucleotide deletion is present in the 3' region of the Reelin message, resulting in a frame shift with production of a predicted protein amputated from its C-terminal amino acids. In this study, we first show that the predicted truncated protein indeed exists in Orleans reeler mice, using several anti-Reelin antibodies. Three antibodies are directed against epitopes located in the N-terminal region of the protein, namely: monoclonal antibody CR-50 [M. Ogawa, T. Miyata, K. Nakajima, K. Yagyu, M. Seike, K. Ikenaka, H. Yamamoto, K. Mikoshiba, The reeler gene-associated antigen on Cajal-Retzius neurons is a crucial molecule for laminar organization of cortical neurons, Neuron 14 (1995) 899-912] (epitope region between Reelin residues 251-407), monoclonal antibody G10 (epitope located between amino acids 199 and 244) and the polyclonal antipeptide rp4 (positions 381-399). A fourth antibody, antipeptide rp5, reacts with the C-terminal (3443-3461) Reelin sequence. In normal embryos, all four antibodies stained cells in the marginal zone with features of Cajal-Retzius cells. While N-terminal specific antibodies detected Reelin immunoreactivity in mouse embryos homozygous for the reeler-Orleans mutation, no staining was obtained with the rp5 antibody, showing the presence of a truncated protein. Moreover, although Reelin could be detected at the surface of living Cajal-Retzius cells of normal mice, it was not revealed after vital staining of embryonic cortex from Orleans reeler mice. These results indicate that the C-terminal region of Reelin is essential for its secretion and suggest that the Orleans reeler phenotype is due to defective Reelin secretion rather than to secretion of an inactive protein.

Amino Acid Sequence↗
PubMed1997

Advanced glycation endproducts stimulate mitogen-activated protein kinase and proliferation in rabbit vascular smooth muscle cells.

Advanced glycation end products of bovine serum albumin (AGEs-BSA) exhibited biphasic effects on the proliferation of cultured rabbit vascular smooth muscle cells (VSMCs) in terms of [3H]thymidine incorporation and cell number count; a stimulatory effect was observed at 1-10 micrograms/ml and an inhibitory effect at more than 20 micrograms/ml, while it inhibited [3H]thymidine incorporation even at 1-10 micrograms/ml in cultured bovine vascular endothelial cells (VECs). Transient activation of p42 mitogen-activated protein kinase (MAPK) with a peak at around 5 min and a subsequent sustained phase was induced by AGEs-BSA in VSMCs, but not in VECs. The dependence of MAPK activation on AGEs-BSA dose was correlated with that of VSMCs proliferation.

Animals↗
PubMed1997

Intermittent divergence of the protein tyrosine kinase family during animal evolution.

The protein tyrosine kinases (PTKs) are a large protein family consisting of many subfamilies with a variety of domain structures. The basic functions are thought to differ for different subfamilies. To know the dates at which the subfamilies diverged by gene duplications, a phylogenetic tree of the PTKs was inferred by comparing sequences from a wide range of species covering diploblasts and triploblasts. The PTK tree revealed that almost all of the gene duplications that gave rise to different subfamilies occurred rapidly before the diploblast-triploblast split, accompanying with rapid amino acid substitutions. This type of gene duplication was, however, rarely observed after that split. Long after the subfamily divergence, another type of gene duplication that gave rise to diverse tissue-specific genes occurred in each subfamily on the chordate lineage since the separation from arthropods. This type of gene duplication occurred frequently before the fish-tetrapod split, accompanying with rapid amino acid substitutions. In contrast, both the frequency of gene duplications and the rate of the amino acid substitutions were considerably reduced after that split. These results strongly suggest that the PTKs diverged intermittently, but not gradually, during animal evolution.

Amino Acids↗