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Biomedical subjects

T Aoyagi

Publications and source records attributed to T Aoyagi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Altered myocardial vasodilatation in patients with hypertriglyceridemia in anatomically normal coronary arteries.

Reduced myocardial vasodilatation (MVD) in hypercholesterolemics without overt coronary stenosis has been reported. However, the status of MVD in hypertriglyceridemics has not yet been clarified. The aim of this study was to investigate whether MVD is impaired in patients with hypertriglyceridemia without overt coronary stenosis. Twenty-three hypertriglyceridemics (10 normocholesterolemic hypertriglyceridemics [HTGs] and 13 mixed combined hyperlipidemics [MCHLs]) and 13 age-matched controls were studied. All patients were proven to have more than one normal coronary artery, as diagnosed by coronary angiography, and those segments that were perfused by anatomically normal coronary arteries were used in the study. Myocardial blood flow (MBF) during dipyridamole (DP) loading and baseline MBF were measured by using positron emission tomography and [13N]ammonia, after which MVD was calculated. Baseline MBF (mL.min(-1).100 g(-1)) was comparable among HTG (76.0+/-26.1), MCHL (77.0+/-26.1), and controls (80.3+/-38.5). However, MBF during DP loading was significantly lower in MCHL (159+/-52.5) than in control subjects (292+/-166, P<.01), while it was comparable in HTG (202+/-104) and controls. MVD was significantly reduced in both HTG (2.70+/-1.09, P<.05) and MCHL (2.07+/-.70, P<.01) compared with controls (3.73+/-1.14). MVD in MCHLs tended to be reduced compared with that in HTGs, but the difference was statistically insignificant (P=.08). There was a significant relationship between MVD and both plasma triglycerides (r=-.47, P<.01) and plasma total cholesterol (r=-.55, P<.01). When controls and HTGs were combined, the relationship between MVD and plasma total triglycerides became more prominent (r=-.55, P<.05), and the significant relationship between cholesterol level and MVD disappeared. Multivariate regression analysis has revealed that the triglyceride level (F=5.2, P<.05) was independently related to MVD (r=.69, P<.01). In conclusion, MVD was reduced in hypertriglyceridemics in anatomically normal coronary arteries. Hypertriglyceridemia is an independent factor for this abnormality.

Aged↗
PubMed1998

Epostatin, new inhibitor of dipeptidyl peptidase II, produced by Streptomyces sp. MJ995-OF5. I. Taxonomy of producing strain, fermentation, isolation, physico-chemical properties and biological properties.

A new inhibitor of dipeptidyl peptidase II (DPP-II, EC 3.4.14.2), designated as epostatin, was discovered in the fermentation broth of a strain isolated in our institute. The strain has been identified as Streptomyces sp. MJ995-OF5 on the basis of taxonomic studies. Epostatin was obtained as a yellow powder after seqential purification by chromatography on Diaion HP-20, n-butanol extraction, Sephadex LH-20 column chromatography and centrifugal partition chromatography (CPC). Epostatin inhibited DPP-II competitively in a dose dependent manner. The compound was slightly inhibitory against other dipeptidyl peptidases.

Alanine↗
PubMed1998

Fluostatins A and B, new inhibitors of dipeptidyl peptidase III, produced by Streptomyces sp. TA-3391. I. Taxonomy of producing strain, production, isolation, physico-chemical properties and biological properties.

New inhibitors of dipeptidyl peptidaseIII (EC 3.4.14.4) from human placenta, designated as fluostatins A and B, were discovered in the fermentation broth of a strain isolated in our institute. The strain has been identified as Streptomyces sp. TA-3391 on the basis of taxonomic studies. Fluostatins A and B were purified by Diaion HP-20 chromatography, ethyl acetate extraction, silica gel chromatography and reverse phase preparative HPLC. With the synthetic substrate, arginyl-arginine-2-naphthylamide, the IC50 values of fluostatins A and B were 0.44 and 24.0 micrograms/ml, respectively. Fluostatins A and B were slightly inhibitory against other dipeptidyl peptidases. Fluostatin A showed mixed-type (competitive and noncompeptitive) inhibition with human leucine-enkephalin as a substrate, and the inhibition constant (Ki) was 14.2 microM.

Chromatography, High Pressure Liquid↗
PubMed1998

[The levels of FDP, FDP-E and D-dimer in patients with rheumatoid arthritis].

We studied the relationship of FDP and D-dimer levels of rheumatoid arthritis (RA) patients with their activities of RA. We evaluated FDP/D-dimer levels of thirty-six RA patients. And we also evaluated FDP/D-dimer levels of 14 patients with systemic lupus erythematosus (SLE) and 12 patients with other rheumatic diseases as control. RA patients were divided into two groups according to their activities. Nineteen patients, who fulfilled at least three of four activities criteria, were classified as active group [RA (A) group], and other 17 patients were classified as not-active group [RA (B) group]. FDP and D-dimer levels of RA patients were higher than those of SLE or other patients group significantly (P < 0.01). Furthermore, in RA patients, high levels of FDP and D-dimer were observed in RA (A) group compared to RA (B) group. In some RA patients, decrease of FDP and D-dimer levels were observed according to their RA activities. FDP and D-dimer levels were not correlated with the level of rheumatoid factor (RF). These results show that the FDP and D-dimer levels were elevated according to RA activity in RA patients.

Adult↗
PubMed1998

[Targeting of anticancer drug using intelligent polymers].

To fabricate the drug targeting system, it is very effective to combine passive targeting with intelligent polymeric system such as temperature-responsive polymers. We have been studying the passive targeting of anticancer drug bonded with or physically trapped in polymeric micelle derived from poly (ethylene oxide) (PEO) and poly (aspartic acid) block copolymer. On the other hand, Poly(N-isopropylacrylamide) (PIPAAm) is known to be a thermo-responsive polymer which has lower critical solution temperature (LCST, 32 degrees C). PIPAAm shows the reversible phase transition above and below LCST. Attempts to apply thermo-responsive drug carriers were made to enhance the site-specificity of polymeric micelle. Namely, novel type of polymeric micelle were prepared from block copolymers comprising N-isopropylacrylamide (IPAAm)-hydrophobic polymers. This temperature responsive micelles were expected to induce selective accumulation controlled by temperature modulation.

Acrylic Resins↗
PubMed1998

Serum amyloid A protein induces production of matrix metalloproteinases by human synovial fibroblasts.

Serum amyloid A (SAA) is a precursor protein for amyloid A, which is a constituent for amyloid fibrils in secondary amyloidosis. To determine the role of SAA in the articular destruction in patients with rheumatoid arthritis (RA), we investigated the effects of SAA on the production of matrix metalloproteinases (MMPs) by rheumatoid synovial fibroblasts. SAA stimulated rheumatoid synovial fibroblasts to produce MMP-2 and MMP-3 in a dose-dependent manner. Pretreatment of synovial fibroblasts with cycloheximide prevented SAA-mediated MMP-2 and MMP-3 secretion. When SAA-containing media were immunodepleted by anti-SAA-specific antibody, SAA-mediated MMP secretion was also abrogated. The level of MMP-3 mRNA was increased in SAA-stimulated synovial fibroblasts compared with that of control cells. Our data indicate that SAA is a potent inducer of MMPs in the RA synovium and may play a critical role in the degradation of extracellular matrix in the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1998

[Chemotherapy for tuberculosis; yesterday, today, and tomorrow--basic and clinical studies].

The discovery of streptomycin in 1944 had given rise to great flowering of chemotherapy for tuberculosis. The times which triple treatment of SM.PAS.INH after the temporal time of SM.PAS had been standard regimens on initial treatment had continued for more than twenty years. The shortening of duration for chemotherapy had become possible by the introduction of RFP, and the duration had reduced to one fourth compared with that of the regimens till then by the addition of PZA for two months at the beginning of treatment on the initial treatment cases. In this paper, historical aspects of early and present-day chemotherapy of tuberculosis and the reports of main studies have been summarized, and pharmacokinetics of INH, action of antituberculous drugs in short-course chemotherapy, MDR-TB and biological response modifiers for treatment of tuberculosis, etc. has been reviewed. It is urgently awaited that more new drugs without cross resistance to previous drugs will be developed for the more shortening of the duration and the improvement of the treatment for MDR-TB.

Aminosalicylic Acid↗
PubMed1997

Hydrogen peroxide-mediated degradation of protein: different oxidation modes of copper- and iron-dependent hydroxyl radicals on the degradation of albumin.

Cupric ions (Cu2+) added to hydrogen peroxide (H2O2) were found to generate hydroxyl radicals (HO) capable of benzoate hydroxylation. Although ferrous (Fe2+) and ferric (Fe3+) ions, when added to H2O2, resulted in very little production of HO, the addition of EDTA to the reaction mixture markedly increased their catalytic activity. In the absence of albumin, catalase (a H2O2 scavenger) and mannitol (an HO radical scavenger) effectively inhibited the formation of HO in H2O2/Cu2+ and H2O2/Fe2+/EDTA oxidation systems. On analysis using SDS-polyacrylamide gel electrophoresis, catalase was shown to prevent the degradation of albumin by both oxidation systems, whereas mannitol was an effective scavenger of the H2O2/Fe2+/EDTA oxidation system but not of the H2O2/Cu2+ oxidation system. Furthermore, the effect of alteration of benzoate hydroxylation and H2O2 consumption on the H2O2/Cu2+ and H2O2/Fe2+/EDTA oxidation systems resulted in opposite behavior that was dependent upon the presence or absence of albumin. These observations suggest that copper ions bind to albumin and induce site-specific degradation by HO generated at the copper-binding site, whereas the Fe2+/EDTA-catalyzed oxidation system induces non-specific degradation of albumin by HO generated by the Fenton reaction between H2O2 and free Fe2+/EDTA in solution.

Albumins↗
PubMed1997

Superantigen-induced stromelysin production from rheumatoid synovial cells.

Superantigens activate a large number of T cells in a V beta-restricted manner after binding to MHC class II molecules on the antigen presenting cells (APC). Superantigens also activate APC directly by interacting with their ligands, MHC class II molecules. In the present study, we examined the effects of superantigens on matrix metalloproteinases (MMPs) secretion from rheumatoid synovial fibroblasts. We demonstrated that stimulation of interferon (IFN)-gamma-treated synovial fibroblasts with staphylococcal enterotoxin A (SEA) selectively induced the secretion of stromelysin, a neutral MMP, from synovial fibroblasts. Pretreatment of synovial fibroblasts with cycloheximide, an inhibitor of protein synthesis, prevented MMP-3 secretion from rheumatoid synovial cells suggesting that protein synthesis was required for SEA-induced MMP-3 secretion after SEA binding to MHC class II molecules. Our data suggest that in the synovium, bacterial superantigens are potent inducers of stromelysin which plays a critical role in articular destruction observed in inflammatory joint disease.

Arthritis, Rheumatoid↗
PubMed1997

Cardiac output and circulating blood volume analysis by pulse dye-densitometry.

OBJECTIVE: Pulse dye-densitometry (PDD) is a newly developed method for monitoring the indocyanine green (ICG) concentration in an artery with which cardiac output (CO) and circulating blood volume (CBV) can be determined. We evaluated its accuracy for clinical use. METHODS: In 7 patients under general anesthesia, ICG-sensitive optical probes (805 and 890 nm) were attached to a finger. Following injection of ICG, the arterial concentration of dye was recorded optically by the non-invasive test instrument and sampled arterial blood ICG concentration was also measured photometrically for comparison. In order to validate the PDD analysis, CO was also measured by both the dye dilution cuvette method and by thermodilution in 8 patients scheduled for coronary artery bypass grafting. In 30 other patients, CBV assessed by PDD was compared with its value estimated from body size. RESULTS: The blood dye concentration correlated well with the values obtained by PDD (r = 0.953, p < 0.01). Mean bias for the test PDD CO was +0.15 +/- 0.72 min l-1 (not significant (n.s.)) compared with the cuvette method while the mean bias of the thermodilution method vs the cuvette method was +0.79 +/- 0.84 min l-1 (p < 0.0001.). The average value of CBV obtained by PDD was 3.81 +/- 1.39 L compared with that estimated value, 3.72 +/- 0.77 L (n.s.). CONCLUSIONS: CO determined by PDD agrees well with cuvette densitometry, and somewhat less well with CO by thermodilution. The new method, by not requiring a pulmonary arterial catheter, is less invasive than either older method, and yields in addition a value of CBV.

Blood Volume↗
PubMed1997

Effects of rapamycin on apoptosis of rheumatoid synovial cells.

In the present study, we investigated the effects of an immunosuppressant, rapamycin, on bcl-2 expression and the susceptibility of human rheumatoid synovial fibroblasts to Fas-mediated apoptosis. Rapamycin treatment down-regulated bcl-2 expression on rheumatoid synovial cells in a dose-dependent manner. In contrast, Fas antigen expression was not influenced by rapamycin treatment. Rapamycin treatment also enhanced the susceptibility of rheumatoid synovial cells to anti-Fas monoclonal antibody-mediated apoptosis. Our results suggest that rapamycin augments the sensitivity of rheumatoid synovial fibroblasts to apoptosis by down-regulating bcl-2 expression. This pharmacological alteration of sensitivity to apoptosis in the rheumatoid synovium may represent a new therapeutic approach for rheumatoid arthritis.

Adult↗
PubMed1997

Inhibitory effects of interleukin-10 on synovial cells of rheumatoid arthritis.

This paper describes the immunoregulatory effects of interleukin-10 (IL-10) on synovial cells in vitro. Synovial cells were cultured with IL-10 in the presence or absence of various cytokines. Following incubation, the costimulatory molecule expression on synovial cells and cytokine production in culture supernatants were analysed by an indirect immunofluorescence method and enzyme-linked immunosorbent assay, respectively. We also examined the effect of IL-10 on the function of synovial cells as antigen-presenting cells (APC). Synovial cells spontaneously express several kinds of costimulatory molecule and produce various kinds of cytokines. Stimulation of synovial cells with interferon-gamma (IFN-gamma), IL-1 beta, or 12-O-tetradecanoyl phorbol 13-acetate (TPA) markedly enhanced the expression of costimulatory molecules and cytokine production of these cells. Both spontaneous and up-regulated costimulatory molecule expression and cytokine production were significantly suppressed by the addition of IL-10. Autologous T-cell proliferation was stimulated by purified protein derivative (PPD) in IFN-gamma-treated synovial cells and treatment of these synovial cells with IL-10 also suppressed T-cell proliferation. Our results suggest that IL-10 has an inhibitory effect on synovial cells and is an important immunoregulatory component of the cytokine network in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1997

Inhibition of carnitine synthesis protects against left ventricular dysfunction in rats with myocardial ischemia.

During myocardial ischemia, inhibition of the carnitine-mediated transportation of fatty acid may be beneficial because it facilitates glucose utilization and prevents an accumulation of fatty acid metabolites. We orally administered 3-(2,2,2-trimethyl hydrazinium) propionate (MET), an inhibitor of carnitine synthesis, for 20 days to rats. Then we evaluated left ventricular (LV) function during brief ischemia by using a buffer-perfused isovolumic heart model. After 15 min of reoxygenation after the transient ischemia, LV peak systolic pressure (PSP) almost completely returned to the baseline level in rats given MET (96 +/- 4%), whereas it was only partially (77 +/- 16%) recovered in the placebo-treated rats. We induced myocardial infarction in other rats by ligating the left anterior descending coronary artery. Then the animals were given MET for 20 days, and LV function was compared. In the placebo-treated rats (with myocardial infarction, but without drug treatment), LVPSP was lower than that in the sham group [108 +/- 19 (n = 10) vs. 136 +/- 15 mm Hg (n = 13); p < 0.05], and the time constant (T) of LV pressure decay was elongated (36 +/- 4 vs. 30 +/- 7 ms; p < 0.05). In MET-treated groups, however, neither PSP nor T differed from those in the sham group. In conclusion, inhibition of the carnitine-mediated transportation of fatty acid by MET protected against left ventricular dysfunction in acute and chronic myocardial ischemia.

Animals↗
PubMed1997

[Clinical evaluation of a reagent for detection of DNA of Mycobacterium tuberculosis complex using the ligase chain reaction (LCR) method].

We evaluated the clinical efficacy of LCR MTB, a reagent developed by Abbott in the USA, in the full automatic ligase chain reaction (LCR) for detection of DNA of M. tuberculosis complex using a thermostable ligase. Using 458 samples isolated from patients with tuberculosis, LCR was compared with a smear method and with a culture method, and was also compared with two other methods of gene amplification, MTD and Amplicor, using 340 and 200 of the 458 samples, respectively. The LCR method detected M. tuberculosis in 49.8% (228/458) of the samples, and was superior to the smear method (31.9%, 146/458) and the culture method (39.1%, 179/458) in sensitivity. The LCR method was also superior to the MTD and Amplicor methods; sensitivity were 37.9% (129/340) for MTD vs. 47.6% (162/340) for LCR, and 56.5% (113/200) for Amplicor vs. 59.5% (119/200) for LCR. These favorable results and the convenience of the LCR method, which enables rapid detection of target genes with a high degree of sensitivity, strongly suggest that LCR MTB is useful as a reagent for detection of M. tuberculosis using nucleic acid amplification.

Adolescent↗