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Biomedical subjects

T Miyata

Publications and source records attributed to T Miyata.

At least 145 records · Page 8Linked to original sources
PubMed2000

Patency after revision surgery for failing infrainguinal vein grafts.

BACKGROUND: Although the results of bypass surgery on arteries in the lower extremities have been greatly improved during the last decades, there are still a significant number of primary failures. In order to investigate the reasons for the failure of autogenous vein grafts after infrainguinal arterial bypass surgery and to ascertain the results of revision operations on the failing grafts, we conducted a clinical study. METHODS: Retrospective study on 104 patients who underwent infrainguinal arterial revascularisation with autogenous veins. RESULTS: One hundred and twenty-six bypasses were constructed in 121 limbs. Seventy-nine of these were for claudication and 47 for threatened limbs (rest pain or ischaemic tissue loss). Five-year primary and secondary patency rates were 69.7% and 84.9% respectively. Spliced or suture-repaired grafts had a poor outcome; five out of seven eventually becoming thrombosed. On the other hand, revision operations for failing but not yet thrombosed grafts produced good results; the five-year primary patency rate after these operations was 76.0%, whereas after single-segment primary grafting it was 72.1%. CONCLUSIONS: These results stress the importance of vigilant follow-up and active intervention for failing grafts. Poor outcome with injured vein grafts emphasizes the importance of meticulous vein harvesting.

Adult↗
PubMed2000

Aortic aneurysm in patients with autoimmune diseases treated with corticosteroids.

BACKGROUND: Aortic aneurysm is a rare but life-threatening cardiovascular complication in patients with autoimmune disorders. The purpose of this study was to clarify the characteristic clinical features and the pathological mechanism of aneurysmal formation in those patients treated with corticosteroids. METHODS: Among 429 patients operated on for abdominal aortic aneurysm during the past 10 years, six patients with autoimmune diseases treated with corticosteroids (one with progressive systemic sclerosis, one with rheumatoid arthritis and four with systemic lupus erythematosus) were reviewed retrospectively. Their data were compared with those of 391 patients with atherosclerotic aneurysms with no autoimmune disorders. The resected aneurysmal walls of the six patients were also compared histopathologically with those of the last six consecutive patients in the control group. RESULTS: The average age of the patients with autoimmune disease was younger than that of the control group (53.8+/-16.6 vs 71.8+/-7.8 years; p<0.05). Patients with autoimmune disease had received long-term corticosteroid therapy for 15-32 years; mean 22.2+/-6.5 years. Pathological examination showed that the destructive change of the medial elastic lamina in the autoimmune disease group was wider than that in the controls. Most patients had no complications in the postoperative follow-up period (5.1+/-3.2 years), while one patient died of rupture of a dissecting aneurysm two years after operation. CONCLUSIONS: Prolonged corticosteroid treatment probably plays a major role in the disintegration of connective tissue of the media, possibly together with primary aortic wall involvement and/or vasculitic damage in patients with autoimmune disorders, which can result in aortic aneurysmal enlargement.

Adrenal Cortex Hormones↗
PubMed1999

Cloning and characterization of a novel human gene encoding a zinc finger protein with 25 fingers.

This study reports cloning and characterization of a human cDNA encoding a novel human zinc finger protein, ZFD25. ZFD25 cDNA is 6118 bp long and has an open reading frame of 2352 bp that encodes a 783 amino acid protein with 25 C2H2-type zinc fingers. The ZFD25 cDNA also contains a region with high sequence similarity to the Krüppel-associated box A and B domain in the 5'-untranslated region, suggesting that ZFD25 belongs to the Krüppel-associated box zinc finger protein family. The ZFD25 gene was localized to chromosome 7q11.2. Northern blot analysis showed that ZFD25 was expressed in a wide range of human organs. In cultured endothelial cells, the mRNA level was decreased upon serum starvation.

Amino Acid Sequence↗
PubMed1999

Commitment and differentiation of osteoclast precursor cells by the sequential expression of c-Fms and receptor activator of nuclear factor kappaB (RANK) receptors.

Osteoclasts are terminally differentiated cells derived from hematopoietic stem cells. However, how their precursor cells diverge from macrophagic lineages is not known. We have identified early and late stages of osteoclastogenesis, in which precursor cells sequentially express c-Fms followed by receptor activator of nuclear factor kappaB (RANK), and have demonstrated that RANK expression in early-stage of precursor cells (c-Fms(+)RANK(-)) was stimulated by macrophage colony-stimulating factor (M-CSF). Although M-CSF and RANKL (ligand) induced commitment of late-stage precursor cells (c-Fms(+)RANK(+)) into osteoclasts, even late-stage precursors have the potential to differentiate into macrophages without RANKL. Pretreatment of precursors with M-CSF and delayed addition of RANKL showed that timing of RANK expression and subsequent binding of RANKL are critical for osteoclastogenesis. Thus, the RANK-RANKL system determines the osteoclast differentiation of bipotential precursors in the default pathway of macrophagic differentiation.

Animals↗
PubMed1999

Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis.

Peritoneal membrane permeability deteriorates in peritoneal dialysis (PD) patients. We test whether glucose degradation products (GDPs) in PD fluids, glyoxal, methylglyoxal and 3-deoxyglucosone, stimulate the production of vascular endothelial growth factor (VEGF), a factor known to enhance vascular permeability and angiogenesis. VEGF increased in cultured rat mesothelial and human endothelial cells exposed to methylglyoxal, but not to glyoxal or 3-deoxyglucosone. VEGF also increased in peritoneal tissue of rats given intraperitoneally methylglyoxal. VEGF and carboxymethyllysine (CML) (formed from GDPs) co-localized immunohistochemically in mesothelial layer and vascular walls of the peritoneal membrane of patients given chronic PD. By contrast, in the peritoneum of non-uremic subjects, VEGF was identified only in vascular walls, in the absence of CML. VEGF production induced by GDPs may play a role in the progressive deterioration of the peritoneal membrane.

Animals↗
PubMed1999

A heuristic approach of maximum likelihood method for inferring phylogenetic tree and an application to the mammalian SOX-3 origin of the testis-determining gene SRY.

Applying the tree bisection and reconnection (TBR) algorithm, we have developed a heuristic method (maximum likelihood (ML)-TBR) for inferring the ML tree based on tree topology search. For initial trees from which iterative processes start in ML-TBR, two cases were considered: one is 100 neighbor-joining (NJ) trees based on the bootstrap resampling and the other is 100 randomly generated trees. The same ML tree was obtained in both cases. All different iterative processes started from 100 independent initial trees ultimately converged on one optimum tree with the largest log-likelihood value, suggesting that a limited number of initial trees will be quite enough in ML-TBR. This also suggests that the optimum tree corresponds to the global optimum in tree topology space and thus probably coincides with the ML tree inferred by intact ML analysis. This method has been applied to the inference of phylogenetic tree of the SOX family members. The mammalian testis-determining gene SRY is believed to have evolved from SOX-3, a member of the SOX family, based on several lines of evidence, including their sequence similarity, the location of SOX-3 on the X chromosome and some aspects of their expression. This model should be supported directly from the phylogenetic tree of the SOX family, but no evidence has been provided to date. A recently published NJ tree shows implausibly remote origin of SRY, suggesting that a more sophisticated method is required for understanding this problem. The ML tree inferred by the present method showed that the SRYs of marsupial and placental mammals form a monophyletic cluster which had diverged from the mammalian SOX-3 in the early evolution of mammals.

Algorithms↗
PubMed1999

Nitric oxide controls src kinase activity through a sulfhydryl group modification-mediated Tyr-527-independent and Tyr-416-linked mechanism.

c-Src kinase was activated when either murine NIH3T3 fibroblast cells or immunoprecipitated c-Src proteins were treated with nitric oxide generator, S-nitroso-N-acetyl penicillamine (SNAP) or sodium nitroprusside. Nitric oxide (NO) scavenger hemoglobin and N(2)O(3) scavenger homocysteine abolished the SNAP-mediated c-Src kinase activation. Phosphoamino acid analysis and peptide mapping of in vitro labeled phospho-c-Src proteins revealed that SNAP promoted the autophosphorylation at tyrosine, which preferentially took place at Tyr-416. Peptide mapping of in vivo labeled c-Src kinase excluded the involvement of phospho-Tyr-527 dephosphorylation in the SNAP-mediated activation mechanism. Correspondingly, protein-tyrosine phosphatase inhibitor Na(3)VO(4) did not abolish the SNAP-mediated activation of Src kinase, and the constitutively activated v-Src kinase was also further up-regulated in activity by SNAP. SNAP, however, failed to up-regulate the kinase activity of Phe-416 mutant v-Src. 2-Mercaptoethanol or dithiothreitol, which should disrupt N(2)O(3)-mediated S-nitrosylation and subsequent formation of the S-S bond, abolished the up-regulated catalytic activity, and the activity was regained after re-exposing the enzyme to SNAP. Exposure of Src kinase to SNAP promoted both autophosphorylation and S-S bond-mediated aggregation of the kinase molecules, demonstrating a linkage between the two events. These results suggest that the NO/N(2)O(3)-provoked S-nitrosylation/S-S bond formation destabilizes the Src structure for Tyr-416 autophosphorylation-associated activation bypassing the Tyr-527-linked regulation.

3T3 Cells↗
PubMed1999

Characterization of CFTR expression in a human pulmonary mucoepidermoid carcinoma cell line, NCI-H292 cells.

The NCI-H292 cell, a human pulmonary mucoepidermoid carcinoma cell line, is commonly used for studying bacterial and viral infections of airway epithelial cells. Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) is the main cause of fetal lung infection in cystic fibrosis patients. In this study, we examined CFTR expression in NCI-H292 cells to determine whether NCI-H292 cells possess sufficient, normally functioning CFTR. The results of RT-PCR and Northern blotting analysis indicated that the CFTR gene expression level was much lower in NCI-H292 cells than in T84 cells. However, Western blotting analysis showed that protein expression in NCI-H292 cells was comparable to that in T84 cells. Furthermore, whole-cell and cell-attached patch clamp electrophysiological techniques indicated that the Cl- current induced by intracellular cAMP elevation in NCI-H292 cells was comparable to that in T84 cells. These findings suggest that NCI-H292 cells with a low level of CFTR gene expression possess enough functional CFTR to show a physiological response.

Base Sequence↗
PubMed1999

Myeloid ELF-1-like factor up-regulates lysozyme transcription in epithelial cells.

Lysozyme is an important component of innate immunity against common pathogens at mucosal surfaces. We previously cloned and characterized the bovine lysozyme 5A (lys5A) promoter with the purpose of determining cis- and trans-acting elements controlling airway epithelial cell-specific expression. We found that such expression is controlled by protein binding to an ETS consensus sequence located approximately at -46 to -40 bp from the transcription start site. The identity of the ETS-related protein responsible for gene transactivation was unknown. In this study, we screened six ETS-related proteins by transient transfection into epithelial cells and fibroblasts. Results showed that among these factors, the myeloid Elf-1-like factor (MEF) was the most potent. Gel shift analysis of epithelial cell nuclear extracts using a lys5A probe including the ETS-binding site (-50/-31) yielded a single band with retarded mobility. This band was supershifted by an antibody directed against MEF. Supporting the possibility that MEF is responsible for functional transactivation of lysozyme in epithelial cells, we found that antisense MEF mRNA decreased lys5A promoter activity and that MEF overexpression in stably transfected cells increased lysozyme mRNA and protein expression. We conclude that MEF is required for epithelial cell transactivation of lysozyme.

Animals↗
PubMed1999

Neurotoxicity of methylglyoxal and 3-deoxyglucosone on cultured cortical neurons: synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases.

In this study, we investigate the neurotoxicity of glycation, particularly early-stage glycation, and its mechanisms, which are possibly synergized with oxidative stress. Methylglyoxal (MG) and 3-deoxyglucosone (3DG), intermediate products of glycation, are known to further accelerate glycation and advanced glycation endproducts (AGEs) formation. Both compounds showed neurotoxicity on cultured cortical neurons and these effects were associated with reactive oxygen species production followed by neuronal apoptosis. Pretreatment with N-acetylcysteine induced neuroprotection against MG and 3DG. Cotreatment, but not pretreatment, with aminoguanidine protected neurons against the neurotoxicities of both compounds. The present study provides the first evidence that MG and 3DG are neurotoxic to cortical neurons in culture. Interference with the process by which glycation and AGEs formation occur may provide new therapeutic opportunities to reduce the pathophysiological changes associated with neurodegeneration, if, as indicated here, the participation of glycoxidation in the pathogenesis of neurodegenerative diseases is essential.

Acetylcysteine↗
PubMed1999

Development of a polyclonal antibody with broad epitope specificity for advanced glycation endproducts and localization of these epitopes in Bruch's membrane of the aging eye.

PURPOSE: To develop an antibody that recognizes a variety of advanced glycation endproduct (AGE) epitopes. METHODS: Glycolaldehyde was used to modify bovine serum albumin and HPLC analysis was used to measure pentosidine formation as an indicator of AGE formation. A polyclonal anti-AGE antibody was synthesized by injecting glycolaldehyde-incubated keyhole limpet hemocyanin into rabbits, affinity purified using AGE modified bovine serum albumin coupled to an affinity resin column, and characterized by immunoblot analysis. RESULTS: HPLC analysis of glycolaldehyde treated bovine serum albumin detected high levels of pentosidine formation, suggesting that glycolaldehyde is a potent precursor for pentosidine. By immunoblot analysis, our antibody recognized carboxymethyllysine and pentosidine, two well-characterized AGEs, as well as other AGE epitopes. Immunohistochemical evaluation showed evidence of AGEs in Bruch's membrane (including basal laminar deposits and drusen), choroidal extracellular matrix, and vessel walls in an 82 year old nondiabetic globe. A similar staining pattern was observed in an age-matched diabetic control. In contrast, no staining was seen with the antibody in a 20 month old nondiabetic globe. CONCLUSIONS: A unique anti-AGE antibody was synthesized that recognizes a variety of AGE epitopes including carboxymethyllysine and pentosidine. Its best use might be in broad surveys of the age-dependent accumulation of a large number of AGE epitopes that might not be revealed by antibodies to pentosidine or CML.

Acetaldehyde↗
PubMed1999

NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus.

NeuroD, a bHLH transcription factor, is implicated in differentiation of neurons and pancreatic beta cells. NeuroD-null mice die shortly after birth due to severe neonatal diabetes. To examine if there is postnatal neuronal phenotype in these mice, we rescued them from neonatal lethality by introducing a transgene encoding the mouse neuroD gene under the insulin promoter. These mice survive to adulthood but display severe neurological phenotype due to neuronal deficit in the granule layers of the cerebellum and hippocampus. We show here that NeuroD is required for these postnatally generated microneurons to undergo proper differentiation, the absence of which results in cell death.

Animals↗
PubMed1999

Effect of Na(+) concentration on the subgel phases of negatively charged phosphatidylglycerol.

The effect of Na(+) concentration on the subgel phase of dimyristoylphosphatidylglycerol (DMPG) was investigated by differential scanning calorimetry (DSC) and negative stain electron microscopy, and the results were compared with dipalmitoylphosphatidylglycerol (DPPG). The conversion mode of DMPG vesicle to the subgel phase by annealing at 5 degrees C was grouped into two types depending on whether Na(+) concentration is above or below 200-250 mM. For [Na(+)]>200-250 mM, the subgel phase of a crystalline superstructure of bilayers wrapped in a cylinder was attained during a 24-h period of annealing and transformed directly to the liquid crystal phase on heating. For [Na(+)]<200-250 mM, two subgel phases which transform to the gel phase on heating were observed after annealing up to 24 h. Both subgel phases showed belt-like structures composed of loosely and closely stacked lamellae, respectively, and their fractions were found to depend on Na(+) concentration. With a further annealing up to 30 days, only the closely stacked subgel phase converted subsequently into the cylindrical superstructure of a more ordered phase. Similar two subgel phases were detected for DPPG at [Na(+)]< or =100 mM. The difference in the relative enthalpy between the gel and subgel phases was investigated from the van der Waals interaction energy between the hydrocarbon chains.

Journal Article↗
PubMed1999

Multiple TGF-beta receptor related genes in sponge and ancient gene duplications before the parazoan-eumetazoan split.

Members of the transforming growth factor beta (TGF-beta) family mediate key events in cell growth and development. Various receptors for diverse members of the TGF-beta family have recently been isolated and sequenced. These receptors form a family (TbetaR family) with a Ser/Thr kinase domain in common. To understand the divergence pattern of the TbetaR family during animal evolution, we have conducted cloning of cDNAs encoding the TbetaR family members from Ephydatia fluviatilis, a freshwater sponge. We obtained seven cDNAs (sALK-1-sALK-7) which are closely related in structure to known family members. Including these sponge sequences, a phylogenetic tree of the family members was inferred by a maximum likelihood method. The phylogenetic tree suggests that the sponge receptors sALK-1-sALK-3, which are closely related to each other, are sponge homologs of vertebrate activin type I receptor (ActR-I). sALK-5 is likely to be a homolog of TGF-beta type II receptor. sALK-4 and sALK-6 might be ancestral precursors of type I and type II receptors, respectively, and sALK-7 is possibly an ancestral precursor of both types. The tree revealed that most, if not all, of the gene duplications that gave rise to known subtypes with distinct ligand specificities antedate the divergence of parazoans and eumetazoans, the earliest divergence of extant animal phyla.

Animals↗
PubMed1999

A reversibly antigen-responsive hydrogel.

Stimuli-responsive hydrogels that undergo abrupt changes in volume in response to external stimuli such as pH, temperature and solvent composition have potential applications in biomedicine and the creation of 'intelligent' materials systems, for example as media for drug delivery, separation processes and protein immobilization. Hydrogels have been reported that respond to pH, temperature, electric fields and saccharides. For some biomedical applications it would be very useful to have a material whose swelling response was dictated by a specific protein. Here we report such a material, which swells reversibly in a buffer solution in response to a specific antigen. The hydrogel was prepared by grafting the antigen and corresponding antibody to the polymer network, so that binding between the two introduces crosslinks in the network. Competitive binding of the free antigen triggers a change in gel volume owing to breaking of these non-covalent crosslinks. In addition, we show that the hydrogel displays shape-memory behaviour, and that stepwise changes in antigen concentration can induce pulsatile permeation of a protein through the network.

Animals↗
PubMed1999

Analysis of 45 episodes of arterial occlusive disease in Japanese patients with congenital protein C deficiency.

Hereditary protein C deficiency is associated with a predisposition to venous thrombosis. It is not clear whether the deficiency is involved in arterial occlusion. In the present study, we screened for protein C amidolytic activity in patients admitted to the National Cardiovascular Center Hospital, and we identified among them 43 probands and 51 relatives with heterozygous protein C deficiency. Among them, 34 patients with heterozygous protein C deficiency had manifested 45 episodes of arterial occlusive disease. Venous thrombotic diseases were less common. In the examination of whether protein C deficiency hastens arterial occlusion, we found a significant difference (p =0.02) in the age at onset of acute myocardial infarction between the patients with protein C deficiency (n=10; 49.4+/-14.8 years) and a group of patients with normal protein C levels (n=42; 60.5+/-10.6 years). Acute myocardial infarction occurred before 40 years of age in a significantly greater proportion of the patients with protein C deficiency (3:10, 30%) as compared with the controls (2:42, 5%) (chi2=5.9, p=0.015). At the onset of atherothrombotic cerebral infarction the patients with protein C deficiency were significantly (p=0.022) younger (n= 11; 57.4+/-12.8 years) than those with normal protein C levels (n=48; 64.6+/-10.1 years). Venous thrombosis was the most frequent clinical manifestation (21 of 31 episodes) in the patients with antithrombin III deficiency (n=26; 68% of the total), who were admitted to our hospital. Thus, our study suggests that congenital protein C deficiency contributes to earlier onset of arterial occlusive diseases, especially acute myocardial infarction, in Japanese subjects.

Adult↗
PubMed1999

2-Isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanilide (OPB-9195) treatment inhibits the development of intimal thickening after balloon injury of rat carotid artery: role of glycoxidation and lipoxidation reactions in vascular tissue damage.

We have pursued the hypothesis that the carbonyl modification of proteins by glycoxidation and lipoxidation reactions plays a role in atherogenesis. Human atherosclerotic tissues with fatty streaks and uremic arteriosclerotic tissues were examined, with specific antibodies, to detect protein adducts formed with carbonyl compounds by glycoxidation or lipoxidation reactions, i.e. advanced glycation end products (AGEs) or glycoxidation products, such as carboxymethyllysine (CML) and pentosidine, and lipoxidation products, such as malondialdehyde (MDA)-lysine and 4-hydroxy-nonenal (HNE)-protein adduct. All the four adducts were identified in the proliferative intima and in macrophage-rich fatty streaks. If the carbonyl modification is not a mere result but is a contributor to atherogenesis, inhibition of glycoxidation and lipoxidation reactions might prevent vascular tissue damage. We tested this hypothesis in rats following balloon injury of their carotid arteries, a model exhibiting a remarkable intimal thickening, which are stained positive for all the four adducts. Oral administration of 2-isopropylidenehydrazono-4-oxo-thiazolidin-5-ylacetanili de (OPB-9195), an inhibitor of both glycoxidation and lipoxidation reactions, in rats following balloon injury effectively prevented the intimal thickening. These data suggest a role for the carbonyl modification of proteins by glycoxidation and lipoxidation reactions in most, if not all, types of vascular tissue damage ('carbonyl stress'), and the usefulness of inhibitors of carbonyl reactions for the treatment of vascular tissue damage.

Aged↗