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T Urano

Publications and source records attributed to T Urano.

At least 55 records · Page 3Linked to original sources
PubMed2000

Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during amlodipine treatment of hypertension in Japanese patients.

Twenty-four Japanese hypertensive patients of both sexes, grouped as having 'medium' and 'high' baseline total lipid values, had their serum lipids, lipoproteins and plasma fibrinolytic parameters, renin and noradrenaline levels determined after 3 months of amlodipine treatment. For the patients with 'medium baseline values', total plasminogen activator inhibitor-1 (PAI-1) and t-PA-PAI-1 complex levels decreased, while the changes in lipids and lipoproteins were not significant after amlodipine treatment. For the patients with 'high baseline values', the mean triglyceride and very low density lipoprotein cholesterol (VLDLC) levels were reduced while the reductions in total and free PAI-1 and the increase in tissue plasminogen (t-PA) levels were not significant after amlodipine treatment. Negative correlations were observed between t-PA and high density lipoprotein cholesterol (HDLC) and HDLC/total cholesterol (TC) ratio in the patients with 'medium baseline values' while t-PA positively correlated with HDLC/TC ratio in patients with 'high baseline values'. The mean levels of renin and noradrenaline remained unchanged before and after amlodipine treatment in the two baseline groups. These findings show that baseline lipid levels of the hypertensive patients could influence lipids and fibrinolytic parameters differently during amlodipine treatment. The baseline lipid levels also influenced the metabolic association between lipids and fibrinolytic function in hypertensive patients during amlodipine treatment. The baseline total lipid values could therefore provide explanations for the complex metabolic interaction between lipids and fibrinolytic function as well as for the antiatherogenic actions of amlodipine treatment in hypertensive patients.

Aged↗
PubMed2000

Influence of baseline values on lipids, lipoproteins and fibrinolytic parameters during treatment of hypertension with cilnidipine.

Sixteen adult hypertensive patients of both sexes, classified as having 'medium' (total lipid profile 240-300 mg dl(-1)), and 'high' (total lipid profile >300 mg dl(-1)) baseline values, underwent serum lipids, lipoproteins and plasma fibrinolytic parameters evaluations after 3 months of cilnidipine treatment. Patients with 'medium baseline values' did not have any change in lipids, lipoproteins and fibrinolytic parameters while patients with 'high baseline values' had beneficial lipid and lipoprotein changes [decreases in total cholesterol (TC), triglycerides (TG), very low density lipoprotein-cholesterol (VLDLC) and increases in high density lipoprotein-cholesterol (HDLC), and HDLC/TC ratio] after cilnidipine treatment. Changes in lipids were negatively associated with fibrinolysis for the patients with 'medium baseline values' and positively associated in patients with 'high baseline values' after cilnidipine treatment. Reduction in blood pressure was related to fibrinolysis and reduced risk of coronary heart disease in the patients with 'high baseline values' after cilnidipine therapy. These results show that during cilnidipine treatment, the baseline lipid profile levels of the patients may influence the lipid altering actions as well as the interaction between lipids and fibrinolysis.

Aged↗
PubMed2000

Serotonergic and kynurenic pathways in rats exposed to foot shock.

Electric foot shock was applied to rats and levels of tryptophan and its metabolites were measured in the plasma, central nervous system and peripheral tissues. Metabolites of tryptophan are the results of the enhancement of serotonergic and kynurenine pathways. Plasma levels of tryptophan increased significantly immediately after the foot shock and returned to normal values within 24 h. Tryptophan levels also increased in all the brain areas immediately after stress application and returned to normal values within 24 h. Foot shock elevated the levels of kynurenine in the plasma, liver, kidney and every parts of the brain. 3-Hydroxykynurenine and kynurenic acid levels were increased in the brain. The present observations suggest that stress activates not only serotonergic pathway but also kynurenine pathway in the central nervous system and periphery. Some metabolites of kynurenine pathway, such as 3-hydroxykynurenine, are neurotoxic while other metabolite, such as kynurenic acid, may be neuroprotective. Increase in serotonin level in the hypothalamus and midbrain stabilises emotion and prevents mood disorders. Therefore, some brain dysfunction resulting from stress may be prevented by the metabolites of tryptophan. The balance of these functions may be important in the maintenance of nerve integrity under stress conditions.

Animals↗
PubMed2000

Coagulation-associated enhancement of fibrinolytic activity via a neutralization of PAI-1 activity.

Total fibrinolytic activity in the vasculature is finely tuned by the balance between tissue plasminogen activator and plasminogen activator inhibitor type 1 (PAI-1). Although PAI-1 targets plasminogen activators, it also reacts with other serine proteases such as thrombin and factor Xa. The latter was shown to interact with PAI-1 only when a physiological concentration of calcium ions (Ca++) is present. Through such interaction, thrombin and Ca++-bound factor Xa shortened fibrin clot lysis times in a purified system by neutralizing PAI-1 activity. Both unfractionated heparin and vitronectin were shown to enhance the clot lysis further. Together with the cleavage and inactivation of PAI-1 by human neutrophil elastase, which was reported previously from our laboratory, such neutralization of PAI-1 activity by these serine proteases was shown to be strongly involved in the coagulation-associated enhancement of fibrinolytic activity.

Anticoagulants↗
PubMed2000

Clinical features of human T-lymphotropic virus type 1 uveitis: a long-term follow-up.

To investigate the clinical manifestations of human T-lymphotropic virus type-1 uveitis (HU), 112 HU patients who were followed up periodically for more than one year were retrospectively analyzed with respect to their ophthalmological and systemic complications. The gender ratio (female/male ratio) of the HU patients was 2.0 and the initial complications were foggy vision in 34.5%, ocular floaters in 33.3%, and blurred vision in 15.5%. As for the ocular symptoms, the majority (78.6%) of patients were classified as intermediate uveitis with vitreous inflammation. Recurrence of uveitis episodes was seen in one half of the patients (51.8%); 12 patients had more than six uveitis episodes. The interval of uveitis episodes varied from two weeks to 10 years. Nearly one half of the patients (43.8%) had ocular complications: e.g., cataract in 22 patients, persistent vitreous opacities in 17 patients, and glaucoma in 16 patients. Although the visual prognosis was essentially good, 11 patients had poor visual prognosis (<0.1). The causes of poor vision in these patients were cataract, cystoid macular edema, epiretinal membrane, and optic nerve atrophy. Of the 112 HU patients, two developed HTLV-I-associated myelopathy (TSP/HAM) after the onset of HU, while none developed adult T-cell leukemia. Sixteen HU patients had a previous history of Graves' disease and a past history of methimazole therapy, while Graves' disease was found in another HU patient only after HU onset and methimazole was not administered before the onset of HU. The present data of long-term follow-up indicate that (1) HU causes various ocular complications and its visual prognosis can be poor, (2) TSP/HAM can be induced even after the onset of HU, and (3) methimazole is not a risk factor of HU after Graves' disease.

Adult↗
PubMed2000

Neutrophil elastase may play a key role in developing symptomatic disseminated intravascular coagulation and multiple organ failure in patients with head injury.

OBJECTIVE: To study the mechanism associated with the development of symptomatic disseminated intravascular coagulation (DIC) after head injury. METHODS: Plasma parameters were analyzed in patients with symptomatic (group A, n = 10) and asymptomatic DIC (group B, n = 15) induced by head injury, and in patients in whom DIC was caused by sepsis (group C, n = 10). RESULTS: Levels of fibrinogen, alpha2PI-plasmin complex and platelets in group A (58.1 mg/dL, 22.4 microg/mL, 16.0 x 10(4)/ mm3) and group B (98.3, 22.1, 16.6 x 10(4)) were comparable, but differed significantly from those in group C (297.4, 2.4, 6.3 x 10(4)). Significant differences were observed between groups A and B in both neutrophil-elastase (1,528 vs. 293 microg/ml) and D-dimer (42.1 vs. 17.6 microg/mL). CONCLUSION: Neutrophil elastase may be implicated in the development of symptomatic DIC after head injury, whose characteristics include "enhanced fibrinolysis with minimal platelet loss."

Adolescent↗
PubMed2000

Acute vs. chronic effects of elevated hemoglobin O(2) affinity on O(2) transport in maximal exercise.

These studies were conducted to compare the effects on systemic O(2) transport of chronically vs. acutely increased Hb O(2) affinity. O(2) transport during maximal normoxic and hypoxic [inspired PO(2) (PI(O(2))) = 70 and 55 Torr, respectively] exercise was studied in rats with Hb O(2) affinity that was increased chronically by sodium cyanate (group 1) or acutely by transfusion with blood obtained from cyanate-treated rats (group 2). Group 3 consisted of normal rats. Hb O(2) half-saturation pressure (P(50); Torr) during maximal exercise was approximately 26 in groups 1 and 2 and approximately 46 in group 3. In normoxia, maximal blood O(2) convection (TO(2 max) = cardiac output x arterial blood O(2) content) was similar in all groups, whereas in hypoxia TO(2 max) was significantly higher in groups 1 and 2 than in group 3. Tissue O(2) extraction (arteriovenous O(2) content/arterial O(2) content) was lowest in group 1, intermediate in group 2, and highest in group 3 (P < 0.05) at all exercise PI(O(2)) values. In normoxia, maximal O(2) utilization (VO(2 max)) paralleled O(2) extraction ratio and was lowest in group 1, intermediate in group 2, and highest in group 3 (P < 0.05). In hypoxia, the lower O(2) extraction ratio values of groups 1 and 2 were offset by their higher TO(2 max); accordingly, their differences in VO(2 max) from group 3 were attenuated or reversed. Tissue O(2) transfer capacity (VO(2 max)/mixed venous PO(2)) was lowest in group 1 and comparable in groups 2 and 3. We conclude that lowering Hb P(50) has opposing effects on TO(2 max) and O(2) extraction ratio, with the relative magnitude of these changes, which varies with PI(O(2)), determining VO(2 max). Although the lower O(2) extraction ratio of groups 2 vs. 3 suggests a decrease in tissue PO(2) diffusion gradient secondary to the low P(50), the lower O(2) extraction ratio of groups 1 vs. 2 suggests additional negative effects of sodium cyanate and/or chronically low Hb P(50) on tissue O(2) transfer.

Animals↗
PubMed2000

[Regulatory mechanism of fibrinolysis system by thrombin activatable fibrinolysis inhibitor (TAFI)].

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a 60-kDa plasma protein that has been shown to be identical to plasma carboxypeptidase B (CPB) and carboxypeptidase U (CPU). TAFI is activated by thrombomodulin (TM)-bound thrombin and specifically removes the C-terminal Lys and Arg by its CPB activity. One of its target substrates is the C-terminal Lys residue in the alpha-chain of plasmin-digested fibrin, which is critical for plasminogen binding to fibrin. Thus, its removal seems to be the main mechanism through which TAFI inhibits fibrinolysis. In this article, relevance of C-terminal Lys of plasmin-digested fibrin in fibrinolysis is described, and then possible roles of TAFI and TM-bound thrombin in a cross-talk between coagulation and fibrinolysis are discussed.

Binding Sites↗
PubMed2000

Replication of enterotropic and polytropic murine coronaviruses in cultured cell lines of mouse origin.

To understand the virus-cell interactions that occur during murine coronavirus infection, six murine cell lines (A3-1M, B16, CMT-93, DBT, IC-21 and J774A.1) were inoculated with eight murine coronaviruses, including prototype strains of both polytropic and enterotropic biotypes, and new isolates. All virus strains produced a cytopathic effect (CPE) with cell-to-cell fusion in B16, DBT, IC-21 and J774A.1 cells. The CPE was induced most rapidly in IC-21 cells and was visible microscopically in all cell lines tested. In contrast, the coronaviruses produced little CPE in A3-1M and CMT-93 cells. Although most virus-infected cells, except KQ3E-infected A3-1M, CMT-93 and J774A.1 cells, produced progeny viruses in the supernatants when assayed by plaque formation on DBT cells, the kinetics of viral replication were dependent on both the cell line and virus strain; replication of prototype strains was higher than that of new isolates. There was no significant difference in replication of enterotropic and polytropic strains. B16 cells supported the highest level of viral replication. To determine the sensitivity of the cell lines to murine coronaviruses, the 50% tissue culture infectious dose of the coronaviruses was determined with B16, DBT, IC-21 and J774A.1 cells, and compared to that with DBT cells. The results indicate that IC-21 cells were the most sensitive to murine coronaviruses. These data suggest that B16 and IC-21 cells are suitable for large-scale preparation and isolation of murine coronaviruses, respectively.

Animals↗
PubMed2000

Applicability of Hyland's Living with Asthma Questionnaire for Japanese asthmatic patients.

OBJECTIVE: To assess the applicability of Hyland's Living with Asthma Questionnaire (LWAQ, 1991), one of the international health-related quality of life scales, for Japanese asthmatic patients with reference to its reproducibility and validity. SUBJECTS AND METHODS: The LWAQ was given to randomly selected asthmatic patients on two occasions separated by a 12-week interval. RESULTS: The mean scale score in the first study (n=304) was 1.83 (range, 1.14-2.77) and logarithmic values of the scores approached normal distribution. The scale scores in the first and second (n=158) studies were well correlated (r=0.81), however, the mean score decreased (0.08) significantly. The questions were further separated into 11 domains. The sex-domain was notable for a low response rate (68%), and scale scores in the sleep-, colds- and sex-domains in the first study varied considerably from those of the other domains. Frequency distributions of scores in the five constructs (Hyland 1996) were not normal and, with the exception of the colds construct, the relations among the remaining four constructs were similar to those previously reported (Hyland 1996). CONCLUSION: Analysis using the mean scale score, domain and construct in the LWAQ is applicable to Japanese asthmatic patients.

Asthma↗
PubMed2000

The cleavage and inactivation of plasminogen activator inhibitor type 1 and alpha2-antiplasmin by reptilase, a thrombin-like venom enzyme.

Reptilase, defibrase and ancrod are thrombin-like venom enzymes that cleave fibrinogen to release fibrinopeptide-A and generate fibrin monomers. Although these enzymes decrease fibrinogen levels in vivo, presumably by enhancing fibrinolytic activity, the mechanism has not been identified. In the present study, we analyzed their effects on the inhibitors of fibrinolysis. Plasminogen activator inhibitor-1 (PAI-1) was cleaved at its C-terminus by reptilase and lost its specific activity. Alpha2-antiplasmin (alpha2-AP) was cleaved both at the Pro19-Leu20 peptide bond and at its C-terminus by reptilase, and also lost its specific activity. The apparent second-order rate constants (mol/l per min per Batroxobin unit) were 0.22 for the cleavage of PAI-1 (3.2 micromol/l) and 0.19 for that of alpha2AP (6.4 micromol/l), which were approximately 200-fold lower than that (47.0) for the cleavage of fibrinogen (1.1 micromol/l). Neither defibrase nor ancrod cleaved and inactivated these inhibitors. Only reptilase enhanced euglobulin clot lysis in vitro at high concentration, due probably to PAI-1 inactivation. Since all these three enzymes enhance fibrinolysis similarly during defibrination therapy, the neutralization or inactivation of the inhibitors of fibrinolysis appeared not to represent the main mechanism for the enhancement.

Ancrod↗
PubMed1999

Larger and more invasive colorectal carcinoma contains larger amounts of plasminogen activator inhibitor type 1 and its relative ratio over urokinase receptor correlates well with tumor size.

BACKGROUND: Considering recent findings that both urokinase plasminogen activator receptor (uPAR) and plasminogen activator inhibitors (PAIs) are involved in tumor growth through an urokinase-type plasminogen activator (uPA) activity-independent mechanism, the relation between the presence of these factors in tumor tissue and the clinicopathologic variables in colorectal carcinoma was reevaluated. METHODS: In 100 colorectal carcinoma patients, antigen levels of u-PA, uPAR, and PAI-1 and PAI-2 were assayed in both tumor tissues and their normal counterparts. Plasma levels of soluble uPAR also were determined. RESULTS: All uPAR, uPA, PAI-1, and PAI-2 antigen levels in tumor tissue were significantly higher than those in normal tissue. Levels of both uPAR and PAI-1 were significantly higher (3.09 +/- 1.37 and 6.63 +/- 7.49, respectively) in large tumors (>/=50 mm in greatest dimension) than those in smaller tumors (< 50 mm) (2.50 +/- 1.07 and 2.72 +/- 2.70, respectively) (P < 0.05). Significant positive correlation coefficients (r) were obtained between tumor size and the calculated ratios of PAI-1/uPAR (r = 0.490; P < 0.0001) and PAI-1/uPA (r = 0. 469; P < 0.0001). In addition to liver metastases (P = 0.004) and lymph node involvement (P = 0.04), high levels of uPAR (P = 0.05) also were found to be of independent prognostic value by multivariate analysis. CONCLUSIONS: Higher expression of uPAR was related to poor prognosis of patients with colorectal carcinoma and excess amounts of PAI-1 over uPAR or uPAR-bound uPA appeared to play an important role in tumor progression.

Adult↗
PubMed1999

Molecular cloning of brain-specific GD1alpha synthase (ST6GalNAc V) containing CAG/Glutamine repeats.

A novel member of the mouse CMP-NeuAc: beta-N-acetylgalactosaminide alpha2,6-sialyltransferase (ST6GalNAc) subfamily, designated ST6GalNAc V, was identified by BLAST analysis of expressed sequence tags. The sequence of the longest cDNA clone of ST6GalNAc V encoded a type II membrane protein with 8 amino acids comprising the cytoplasmic domain, 21 amino acids comprising the transmembrane region, and 306 amino acids comprising the catalytic domain. The predicted amino acid sequence showed homology to the previously cloned ST6GalNAc III and IV, with common amino acid sequences in sialyl motifs L and S among these three enzymes. Eleven CAG repeats were found in the stem region. A fusion protein with protein A and extracts from L cells transfected with ST6GalNAc V in a expression vector showed enzyme activity of alpha2,6-sialyltransferase almost exclusively for GM1b, but not toward glycoproteins. Sialidase treatment and thin layer chromatography immunostaining revealed that the product was GD1alpha. Northern blotting revealed that three transcripts of the gene were expressed specifically in brain tissues. It is concluded that this enzyme is involved in the synthesis of GD1alpha in the nervous tissues, and the CAG repeats may have implications in neurodegenerative diseases.

Amino Acid Sequence↗
PubMed1999

Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene.

Progeroid type Ehlers-Danlos (E-D) syndrome was reported to be caused by defects in galactosyltransferase I (EC 2.4.1.133), which is involved in the synthesis of common linkage regions of proteoglycans. Recently, we isolated cDNA of the galactosyltransferase I (XGalT-1) (Okajima, T., Yoshida, K., Kondo, T., and Furukawa, K. (1999) J. Biol. Chem. 274, 22915-22918). Therefore, we analyzed mutations in this gene of a patient with progeroid type E-D syndrome by reverse transcription polymerase chain reaction and direct sequencing. Two changes of G and T to A and C at 186 and 206, respectively, were detected. Then, we determined the genomic DNA sequences encompassing the A186D and L206P mutations, revealing that the unaffected parents and two siblings were heterozygous for either one of the two different mutations and normal, while the patient had both of two different mutant genes. Enzymatic functions of cDNA clones of XGalT-1 containing the individual mutations were examined, elucidating that L206P clone completely lost the activity, while A186D retained approximately 50% or 10% of the activity when analyzed with extracts from cDNA transfectant cells or recombinant soluble enzymes, respectively. Moreover, L206P enzyme showed diffuse staining in the cytoplasm of transfectant cells, while the wild type or A186D clones showed Golgi pattern. These results indicated that the mutations in XGalT-1 were at least one of main molecular basis for progeroid type E-D syndrome.

Amino Acid Sequence↗
PubMed1999

Molecular cloning of rat efp: expression and regulation in primary osteoblasts.

We have previously identified an estrogen-responsive gene, efp (estrogen-responsive finger protein), by genomic binding-site cloning method. Here, we isolated a rat homologue of efp cDNA that encodes an open reading frame of 644 amino acids sharing high homology with human efp (69% identity at the protein level) and mouse efp (80% identity at the protein level). The efp protein has a RING finger, a variant type of zinc finger motif, B1 box and B2 box, each having a pair of zinc fingers, and coiled-coil domain, belonging to the RING finger-B box-Coiled Coil (RBCC) family. Several members of RBCC family including efp have characteristic C-terminal domain, forming a subfamily. Next, we detected efp mRNA in primary osteoblasts, one of estrogen target cells, derived from the calvariae of rat fetus. An anti-efp antibody revealed the efp protein is expressed and regulated by estrogen in the primary osteoblasts. Interestingly, the efp protein in primary osteoblasts is down-regulated by 1alpha,25-dihydroxyvitamin D(3) treatment that promotes the differentiation of the cells, whereas it is up-regulated by TGF-beta1 treatment that inhibits the differentiation of the cells. These findings suggest the possible involvement of the efp in the differentiation of osteoblastic cells.

Amino Acid Sequence↗
PubMed1999

Association of bone mineral density with a polymorphism of the peroxisome proliferator-activated receptor gamma gene: PPARgamma expression in osteoblasts.

The peroxisome proliferator-activated receptor gamma (PPARgamma) protein as well as its transcript was detected in primary osteoblasts derived from rat calvariae. To analyze the possible involvement of PPARgamma in the human bone metabolism, association between bone mineral density (BMD) and a polymorphism of PPARgamma gene was investigated in Japanese postmenopausal women. We examined a polymorphism corresponding to a silent C --> T transition located in exon 6 of the PPARgamma gene, that was previously reported to be associated with plasma leptin levels in the obese. The frequencies of the C and T alleles in the population studied here were 0.851 and 0.149, respectively. When we separated the subjects into two groups, one bearing at least one T allele (CT + TT) and the other which did not (CC), the former subjects had lower BMD (Z score of total body; 0.056 +/- 1.00. L2-4; -0.25 +/- 1.26, mean +/- standard deviation). These data suggest that there is an association between the restriction fragment length polymorphism (RFLP) of PPARgamma gene and BMD and the possible involvement of this single nucleotide polymorphism (SNP) in the cause of postmenopausal osteoporosis in Japanese women.

Aged↗